Blue Ribbon Committee II: Report of the Subcommittee on Faculty Development and Educational Support.

The American College of Surgeons, American Board of Surgery, and the American Surgical Association have created a Blue Ribbon Committee II to evaluate the current status of surgical education in the United States. As part of this endeavor, a subcommittee was formed to address issues pertinent to development of surgical faculty as teachers. This entailed multiple discussions among a group of experienced surgical educators, a review of the literature, and a delphi analysis of possible suggested improvements for faculty educational support, resulting in a final set of recommendations for improvement for future surgical faculty development. These recommendations include a task force to establish a validated system of compensation for faculty teaching, a task force to determine an accurate assessment of the value of surgical trainees to health systems, a review by the Surgical Residency Review Committee and the Association of Program Directors in Surgery of minimal faculty resources for program accreditation in the area of teaching learners, collaborative efforts across surgical specialties for the definition of a national curriculum for faculty, and development of a tool for evaluation of faculty teaching performance.

The Blue Ribbon Committee II Report and Recommendations on Surgical Education and Training in the United States: 2024.

OBJECTIVE: An expert panel made recommendations to optimize surgical education and training based on the effects of contemporary challenges. BACKGROUND: The inaugural Blue Ribbon Committee (BRC I) proposed sweeping recommendations for surgical education and training in 2004. In light of those findings, a second BRC (BRC II) was convened to make recommendations to optimize surgical training considering the current landscape in medical education. METHODS: BRC II was a panel of 67 experts selected on the basis of experience and leadership in surgical education and training. It was organized into subcommittees which met virtually over the course of a year. They developed recommendations, along with the Steering Committee, based on areas of focus and then presented them to the entire BRC II. The Delphi Method was chosen to obtain consensus, defined as>80% agreement amongst the panel. Cronbach alpha was computed to assess the internal consistency of three Delphi rounds. RESULTS: Of 50 recommendations, 31 obtained consensus in the following aspects of surgical training (# consensus recommendation /# proposed): Workforce (1/5), Medical Student Education (3/8), Work Life Integration (4/6), Resident Education (5/7), Goals, Structure and Financing of Training (5/8), Education Support and Faculty Development (5/6), Research Training (7/9), and Educational Technology and Assessment (1/1). The internal consistency was good in Rounds 1 and 2 and acceptable in Round 3. CONCLUSIONS: BRC II used the Delphi approach to identify and recommend 31 priorities for surgical education in 2024. We advise establishing a multidisciplinary surgical educational group to oversee, monitor and facilitate implementation of these recommendations.

Transforming the Future of Surgeon-Scientists.

OBJECTIVE: To create a blueprint for surgical department leaders, academic institutions, and funding agencies to optimally support surgeon-scientists. BACKGROUND: Scientific contributions by surgeons have been transformative across many medical disciplines. Surgeon-scientists provide a distinct approach and mindset toward key scientific questions. However, lack of institutional support, pressure for increased clinical productivity, and growing administrative burden are major challenges for the surgeon-scientist, as is the time-consuming nature of surgical training and practice. METHODS: An American Surgical Association Research Sustainability Task Force was created to outline a blueprint for sustainable science in surgery. Leaders from top NIH-sponsored departments of surgery engaged in video and in-person meetings between January and April 2023. A strength, weakness, opportunities, threats analysis was performed, and workgroups focused on the roles of surgeons, the department and institutions, and funding agencies. RESULTS: Taskforce recommendations: (1) SURGEONS: Growth mindset : identifying research focus, long-term planning, patience/tenacity, team science, collaborations with disparate experts; Skill set : align skills and research, fill critical skill gaps, develop team leadership skills; DEPARTMENT OF SURGERY (DOS): (2) MENTORSHIP: Chair : mentor-mentee matching/regular meetings/accountability, review of junior faculty progress, mentorship training requirement, recognition of mentorship (eg, relative value unit equivalent, awards; Mentor: dedicated time, relevant scientific expertise, extramural funding, experience and/or trained as mentor, trusted advisor; Mentee : enthusiastic/eager, proactive, open to feedback, clear about goals; (3) FINANCIAL SUSTAINABILITY: diversification of research portfolio, identification of matching funding sources, departmental resource awards (eg, T-/P-grants), leveraging of institutional resources, negotiation of formalized/formulaic funds flow investment from academic medical center toward science, philanthropy; (4) STRUCTURAL/STRATEGIC SUPPORT: Structural: grants administrative support, biostats/bioinformatics support, clinical trial and research support, regulatory support, shared departmental laboratory space/equipment; Strategic: hiring diverse surgeon-scientist/scientists faculty across DOS, strategic faculty retention/ recruitment, philanthropy, career development support, progress tracking, grant writing support, DOS-wide research meetings, regular DOS strategic research planning; (5) COMMUNITY AND CULTURE: Community: right mix of faculty, connection surgeon with broad scientific community; Culture: building research infrastructure, financial support for research, projecting importance of research (awards, grand rounds, shoutouts); (6) THE ROLE OF INSTITUTIONS: Foundation: research space co-location, flexible start-up packages, courses/mock study section, awards, diverse institutional mentorship teams; Nurture: institutional infrastructure, funding (eg, endowed chairs), promotion friendly toward surgeon-scientists, surgeon-scientists in institutional leadership positions; Expectations: RVU target relief, salary gap funding, competitive starting salaries, longitudinal salary strategy; (7) THE ROLE OF FUNDING AGENCIES: change surgeon research training paradigm, offer alternate awards to K-awards, increasing salary cap to reflect market reality, time extension for surgeon early-stage investigator status, surgeon representation on study section, focused award strategies for professional societies/foundations. CONCLUSIONS: Authentic recommitment from surgeon leaders with intentional and ambitious actions from institutions, corporations, funders, and society is essential in order to reap the essential benefits of surgeon-scientists toward advancements of science.

Development of pro-angiogenic skin substitutes for wound healing.

Wounds pose significant challenges to public health, primarily due to the loss of the mechanical integrity and barrier function of the skin and impaired angiogenesis, causing physical morbidities and psychological trauma to affect patients. Reconstructing the vasculature of the wound bed is crucial for promoting wound healing, reducing scar formation and enhancing the quality of life for patients. The development of pro-angiogenic skin substitutes has emerged as a promising strategy to facilitate vascularization and expedite the healing process of burn wounds. This review provides an overview of the various types of skin substitutes employed in wound healing, explicitly emphasising those designed to enhance angiogenesis. Synthetic scaffolds, biological matrices and tissue-engineered constructs incorporating stem cells and primary cells, cell-derived extracellular vesicles (EVs), pro-angiogenic growth factors and peptides, as well as gene therapy-based skin substitutes are thoroughly examined. The review summarises the existing challenges, future directions and potential innovations in pro-angiogenic dressing for skin substitutes. It highlights the need for continued research to develop new technologies and combine multiple strategies and factors, and to overcome obstacles and advance the field, ultimately leading to improved outcomes for wound patients.

Surgical Education.

This paper summarizes the proceedings of the joint European Surgical Association ESA/American Surgical Association symposium on Surgical Education that took place in Bordeaux, France, as part of the celebrations for 30 years of ESA scientific meetings. Three presentations on the use of quantitative metrics to understand technical decisions, coaching during training and beyond, and entrustable professional activities were presented by American Surgical Association members and discussed by ESA members in a symposium attended by members of both associations.

Experience of a single academic institution with the National Accreditation Program for Rectal Cancer and the resulting improvement in care.

AIM: The American College of Surgeons Committee on Cancer developed the National Accreditation Program for Rectal Cancer (NAPRC) to reduce variations in rectal cancer care, standardize clinical practice and encourage multidisciplinary approaches. The aim of this study was to analyse if accreditation achieved a higher quality of care at one hospital. METHOD: The University of California Davis Medical Center was accredited in 2019. A retrospective review of rectal adenocarcinoma patients was performed between the years 2013 and 2018. Patients presenting from 2013 to 2015 were discussed at a gastrointestinal tumour board while patients in 2018 had an accredited rectal cancer tumour board. Patients from 2016 to 2017 were excluded as the programme was still developing. Compliance to the NAPRC standards was compared between the cohorts. RESULTS: One hundred and thirty patients were evaluated, 88 (68%) in the prerectal tumour board cohort and 42 (32%) in the rectal tumour board cohort. The prerectal tumour board cohort often failed to meet attendance standards. All patients in the rectal tumour board cohort met all criteria. Similarly, clinical service compliance improved in the rectal tumour board cohort for 13 metrics, 10 of which were statistically significant. Although a high proportion of patients in both groups experienced quality surgery, i.e. complete total mesorectal excision and negative margins, the lack of complete pathological reporting in the prerectal tumour board cohort limited analysis. CONCLUSION: Multidisciplinary rectal cancer tumour boards are associated with improved compliance with recommended care by the NAPRC. Patients discussed at a rectal cancer tumour board were more likely to receive appropriate staging, coordinated care and have better clinical documentation.

Evolution and Variations of the Ovine Model of Spina Bifida.

Spina bifida is the most common congenital anomaly of the central nervous system and the first non-fatal fetal lesions to be addressed by fetal intervention. While research in spina bifida has been performed in rodent, nonhuman primate, and canine models, sheep have been a model organism for the disease. This review summarizes the history of development of the ovine model of spina bifida, previous applications, and translation into clinical studies. Initially used by Meuli et al. [Nat Med. 1995;1(4):342-7], fetal myelomeningocele defect creation and in utero repair demonstrated motor function preservation. The addition of myelotomy in this model can reproduce hindbrain herniation malformations, which is the leading cause of mortality and morbidity in humans. Since inception, the ovine models have been validated numerous times as the ideal large animal model for fetal repair, with both locomotive scoring and spina bifida defect scoring adding to the rigor of this model. The ovine model has been used to study different methods of myelomeningocele defect repair, the application of various tissue engineering techniques for neuroprotection and bowel and bladder function. The results of these large animal studies have been translated into human clinical trials including Management of Meningocele Study (MOMS) trial that established current standard of care for prenatal repair of spina bifida defects, and the ongoing trials including the Cellular Therapy for In Utero Repair of Myelomeningocele (CuRe) trial using a stem cell patch for repair. The advancement of these life savings and life-altering therapies began in sheep models, and this notable model continues to be used to further the field including current work with stem cell therapy.

Impact of Gestational Age on Neuroprotective Function of Placenta-Derived Mesenchymal Stromal Cells.

INTRODUCTION: The Management of Myelomeningocele Study demonstrated that in utero repair of myelomeningocele improved motor outcomes compared with postnatal repair. However, even after in utero repair, many children were still unable to walk. We have previously demonstrated that augmentation of in utero repair with early-gestation placental mesenchymal stromal cells (PMSCs) improves motor outcomes in lambs compared with standard in utero repair. The neuroprotective potential of PMSCs of all gestational ages has not been evaluated previously. METHODS: PMSCs were isolated from discarded first trimester (n = 3), second trimester (n = 3), and term (n = 3) placentas by explant culture. Cytokine array analysis was performed. Secretion of two neurotrophic factors, brain-derived neurotrophic factor and hepatocyte growth factor, was evaluated by enzyme-linked immunosorbent assay. An in vitro neuroprotective assay demonstrated to be associated with in vivo function was performed. RESULTS: All cell lines secreted immunomodulatory and neuroprotective cytokines and secreted the neurotrophic factors evaluated. Increased neuroprotective capabilities relative to no PMSCs were demonstrated in two of the three first trimester cell lines (5.61, 4.96-6.85, P < 0.0001 and 2.67, 1.67-4.12, P = 0.0046), two of the three second trimester cell lines (2.82, 2.45-3.43, P = 0.0004 and 3.25, 2.62-3.93, P < 0.0001), and two of the three term cell lines (2.72, 2.32-2.92, P = 0.0033 and 2.57, 1.41-4.42, P = 0.0055). CONCLUSIONS: We demonstrated variation in neuroprotective function between cell lines and found that some cell lines from each trimester had neuroprotective properties. This potentially expands the donor pool of PMSCs for clinical use. Further in-depth studies are needed to understand potential subtle differences in cell function at different gestational ages.

National surgical, obstetric, anaesthesia and nursing plan, Nigeria.

Recent evidence suggests that strengthening surgical care within existing health systems will strengthen the overall health-care system. However, Nigeria's national strategic health development plan 2018-2022 placed little emphasis on surgical care. To address the gap, we worked with professional societies and other partners to develop the national surgical, obstetric, anaesthesia and nursing plan 2019-2023. The aim was to foster actions to prioritize surgical care for the achievement of universal health coverage. In addition to creating a costed strategy to strengthen surgical care, the plan included children's surgery and nursing: two key aspects that have been neglected in other national surgical plans. Pilot implementation of the plan began in 2020, supported by a nongovernmental organization with experience in surgical care in the region. We have created specific entry points to facilitate the pilot implementation. In the pilot, an electronic surgery registry has been created; personnel are being trained in life support; nurses are being trained in safe perioperative care; biomedical technicians and sterile supplies nurses are being trained in surgical instrument repair and maintenance; and research capacity is being strengthened. In addition, the mainstream media are being mobilized to improve awareness about the plan among policy-makers and the general population. Another development partner is interested in providing support for paediatric surgery, and a children's hospital is being planned. As funding is a key challenge to full implementation, we need innovative domestic funding strategies to support and sustain implementation.

De récentes preuves suggèrent que le renforcement des soins chirurgicaux au sein des systèmes de santé existants entraînera un renforcement du système tout entier. Pourtant, le plan 2018­2022 de développement stratégique de la santé au Nigeria n'accorde que peu d'importance à ces soins. Pour remédier au problème, nous avons travaillé avec des associations professionnelles ainsi que d'autres partenaires afin de mettre au point le plan national de chirurgie, d'obstétrique, d'anesthésie et de soins infirmiers 2019­2023. Objectif: favoriser les mesures privilégiant les soins chirurgicaux, en vue d'offrir une couverture maladie universelle. Outre l'élaboration d'une stratégie chiffrée servant à consolider le secteur, le plan a intégré les unités de soins infirmiers et de chirurgie pédiatrique, deux aspects clés qui ont été négligés dans d'autres plans nationaux relatifs à la chirurgie. La mise en œuvre de la version pilote du plan a démarré en 2020, avec l'aide d'une organisation non gouvernementale possédant de l'expérience en matière d'interventions chirurgicales dans la région. Nous avons établi des points de départ spécifiques pour faciliter cette mise en œuvre. Dans le cadre de la version pilote, un registre de chirurgie électronique a été créé; le personnel a été formé à l'assistance vitale; les infirmiers ont découvert comment administrer des soins périopératoires sûrs; les techniciens biomédicaux et les infirmiers en stérilisation du matériel ont appris à réparer les instruments chirurgicaux; et enfin, les capacités de recherche et de maintenance ont été revues à la hausse. Par ailleurs, les médias traditionnels ont été sollicités afin d'informer les législateurs et la population en général au sujet du plan. Un partenaire de développement supplémentaire a proposé son aide en matière de chirurgie pédiatrique, et un hôpital pour enfants est prévu. Les fonds constituant l'un des principaux défis d'une mise en œuvre complète, nous avons besoin de stratégies de financement innovantes à l'échelle nationale pour la soutenir et la maintenir.

Las evidencias recientes sugieren que el fortalecimiento de la atención quirúrgica dentro de los sistemas sanitarios existentes reforzará el sistema general de la atención sanitaria. Sin embargo, el plan nacional estratégico para el desarrollo de la salud 2018-2022 de Nigeria dio poca importancia a la atención quirúrgica. Para abordar esta carencia, trabajamos con sociedades profesionales y otros asociados con el fin de elaborar el plan nacional de intervención quirúrgica, obstetricia, anestesia y enfermería 2019-2023. El objetivo era impulsar acciones para priorizar la atención quirúrgica en pro del logro de la cobertura sanitaria universal. Además de crear una estrategia con costes para reforzar la atención quirúrgica, el plan incluía intervenciones quirúrgicas y cuidados de enfermería para niños, que son dos aspectos clave que se han ignorado en otros planes nacionales de intervención quirúrgica. La implementación piloto del plan comenzó en 2020, con el apoyo de una organización no gubernamental que tiene experiencia en la atención quirúrgica en la región. Se han creado puntos iniciales específicos para facilitar la implementación piloto. En el plan piloto, se ha creado un registro electrónico de intervenciones quirúrgicas; se está capacitando al personal en apoyo vital; se está capacitando al personal de enfermería en cuidados perioperatorios seguros; se está capacitando a los técnicos biomédicos y al personal de enfermería de suministros estériles en la restauración de instrumentos quirúrgicos; y se está fortaleciendo la capacidad de mantenimiento e investigación. Además, se está recurriendo a los principales medios de comunicación para dar a conocer el plan a los responsables de formular las políticas y a la población en general. Otro asociado para el desarrollo está interesado en prestar apoyo a la intervención quirúrgica pediátrica, y se está planificando un hospital infantil. Como el financiamiento es un desafío clave para implementar el plan en su totalidad, se requieren estrategias innovadoras de financiamiento nacional para apoyar y sostener la implementación.

Society for Maternal-Fetal Medicine Consult Series #59: The use of analgesia and anesthesia for maternal-fetal procedures.

Pain is a complex phenomenon that involves more than a simple physical response to external stimuli. In maternal-fetal surgical procedures, fetal analgesia is used primarily to blunt fetal autonomic responses and minimize fetal movement. The purpose of this Consult is to review the literature on what is known about the potential for fetal awareness of pain and to discuss the indications for and the risk-benefit calculus involved in the use of fetal anesthesia and analgesia. The recommendations by the Society for Maternal-Fetal Medicine are as follows: (1) we suggest that fetal paralytic agents be considered in the setting of intrauterine transfusion, if needed, for the purpose of decreasing fetal movement (GRADE 2C); (2) although the fetus is unable to experience pain at the gestational age when procedures are typically performed, we suggest that opioid analgesia should be administered to the fetus during invasive fetal surgical procedures to attenuate acute autonomic responses that may be deleterious, avoid long-term consequences of nociception and physiological stress on the fetus, and decrease fetal movement to enable the safe execution of procedures (GRADE 2C); and (3) due to maternal risk and a lack of evidence supporting benefit to the fetus, we recommend against the administration of fetal analgesia at the time of pregnancy termination (GRADE 1C).

Placental Mesenchymal Stromal Cells: Preclinical Safety Evaluation for Fetal Myelomeningocele Repair.

BACKGROUND: Myelomeningocele (MMC) is the congenital failure of neural tube closure in utero, for which the standard of care is prenatal surgical repair. We developed clinical-grade placental mesenchymal stromal cells seeded on a dural extracellular matrix (PMSC-ECM), which have been shown to improve motor outcomes in preclinical ovine models. To evaluate the long-term safety of this product prior to use in a clinical trial, we conducted safety testing in a murine model. METHODS: Clinical grade PMSCs obtained from donor human placentas were seeded onto a 6 mm diameter ECM at a density of 3 × 105 cells/cm2. Immunodeficient mice were randomized to receive either an ECM only or PMSC-ECM administered into a subcutaneous pocket. Mice were monitored for tumor formation until two study endpoints: 4 wk and 6 mo. Pathology and histology on all tissues was performed to evaluate for tumors. Quantitative polymerase chain reaction (qPCR) was performed to evaluate for the presence of human DNA, which would indicate persistence of PMSCs. RESULTS: Fifty-four mice were included; 13 received ECM only and 14 received PMSC-ECM in both the 4-wk and 6-mo groups. No mice had gross or microscopic evidence of tumor development. A nodular focus of mature fibrous connective tissue was identified at the subcutaneous implantation pocket in the majority of mice with no significant difference between ECM only and PMSC-ECM groups (P = 0.32 at 4 wk, P > 0.99 at 6 mo). Additionally, no human DNA was detected by qPCR in any mice at either time point. CONCLUSIONS: Subcutaneous implantation of the PMSC-ECM product did not result in tumor formation and we found no evidence that PMSCs persisted. These results support the safety of the PMSC-ECM product for use in a Phase 1/2a human clinical trial evaluating fetal MMC repair augmented with PMSC-ECM.

Impact of prescription drug monitoring program mandate on postoperative opioid prescriptions in children.

PURPOSE: Prescription drug monitoring programs (PDMPs) have been established to combat the opioid epidemic, but there is no data on their efficacy in children. We hypothesized that a statewide PDMP mandate would be associated with fewer opioid prescriptions in pediatric surgical patients. METHODS: Patients < 18 undergoing inguinal hernia repair, orchiopexy, orchiectomy, appendectomy, or cholecystectomy at a tertiary children's hospital were included. The primary outcome, discharge opioid prescription, was compared for 10 months pre-PDMP (n = 158) to 10 months post-PDMP (n = 228). Interrupted time series analysis was performed to determine the effect of the PDMP on opioid prescribing. RESULTS: Over the 20-month study period, there was an overall decrease in the rate of opioid prescriptions per month (- 3.6% change, p < 0.001). On interrupted time series analysis, PDMP implementation was not associated with a significant decrease in the monthly rate of opioid prescriptions (1.27% change post-PDMP, p = 0.4). However, PDMP implementation was associated with a reduction in opioid prescriptions of greater than 5 days' supply (- 2.7% per month, p = 0.03). CONCLUSION: Opioid prescriptions declined in pediatric surgical patients over the study time period. State-wide PDMP implementation was associated with a reduction in postoperative opioid prescriptions of more than 5 days' duration.

Inclusion of Children's Surgery in National Surgical Plans and Child Health Programmes: the need and roadmap from Global Initiative for Children's Surgery.

About 1.7 billion children and adolescents, mostly in low- and middle-income countries (LMICs) lack access to surgical care. While some of these countries have developed surgical plans and others are in the process of developing theirs, children's surgery has not received the much-needed specific emphasis and focus in these plans. With the significant burden of children's surgical conditions especially in low- and middle-income countries, universal health coverage and the United Nations' (UN) Sustainable Development Goals (SDG) will not be achieved without deliberate efforts to scale up access to children's surgical care. Inclusion of children's surgery in National Surgical Obstetric and Anaesthesia Plans (NSOAPs) can be done using the Global Initiative for Children's Surgery (GICS)-modified Children's Surgical Assessment Tool (CSAT) tool for baseline assessment and the Optimal Resources for Children Surgical Care (OReCS) as a foundational tool for implementation.

A Novel Model of Fetal Spinal Cord Exposure Allowing for Long-Term Postnatal Survival.

BACKGROUND: The inherent morbidity associated with fetal ovine models of myelomeningocele (MMC) has created challenges for long-term survival of lambs. We aimed to develop a fetal ovine surgical spinal exposure model which could be used to evaluate long-term safety after direct spinal cord application of novel therapeutics for augmentation of in utero MMC repair. METHODS: At gestational age (GA) 100-106, fetal lambs underwent surgical intervention. Laminectomy of L5-L6 was performed, dura was removed, and an experimental product was directly applied to the spinal cord. Paraspinal muscles and skin were closed and the fetus was returned to the uterus. Lambs were delivered via cesarean section at GA 140-142. Lambs were survived for 3 months with regular evaluation of motor function by the sheep locomotor rating scale. Spinal angulation was evaluated by magnetic resonance imaging at 2 weeks and 3 months. RESULTS: Five fetal surgical intervention lambs and 6 control lambs who did not undergo surgical intervention were included. All lambs survived to the study endpoint of 3 months. No lambs had motor function abnormalities or increased spinal angulation. CONCLUSION: This model allows for long-term survival after fetal spinal cord exposure with product application directly onto the spinal cord.

Fetal Surgery in the Primate 4.0: A New Technique 30 Years Later.

INTRODUCTION: Open fetal surgery requires a hemostatic hysterotomy that minimizes membrane separation. For over 30 years, the standard of care for hysterotomy in the gravid uterus has been the AutoSuture Premium Poly CS*-57 stapler. OBJECTIVE: In this study, we sought to test the feasibility of hysterotomy in a rhesus monkey model with the Harmonic ACE®+7 Shears. METHODS: A gravid rhesus monkey underwent midgestation hysterotomy at approximately 90 days of gestation (2nd trimester; term = 165 ± 10 days) using the Harmonic ACE®+7 Shears. A two-layer uterine closure was completed and the dam was monitored by ultrasound intermittently throughout the pregnancy. At 58 days after hysterotomy (near term), a final surgery was performed to evaluate the uterus and hysterotomy site. RESULTS: A 3.5-cm hysterotomy was completed in 2 min 7 s. The opening was hemostatic and the membranes were sealed. Immediately after closure and throughout the pregnancy, ultrasound revealed intact membranes without separation and normal amniotic fluid levels. At term, the scar was well healed without signs of thinning or dehiscence. CONCLUSIONS: The Harmonic ACE®+7 Shears produced a hemostatic midgestation hysterotomy with membrane sealing in the rhesus monkey model. Importantly, healing was acceptable.

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.

Surviving Lambs with Myelomeningocele Repaired in utero with Placental Mesenchymal Stromal Cells for 6 Months: A Pilot Study.

BACKGROUND: Fetal repair of myelomeningocele (MMC) with placental mesenchymal stromal cells (PMSCs) rescues ambulation in the ovine model up to 48 h postnatally. Outcomes past 48 h are unknown as MMC lambs have not been survived past this timepoint. OBJECTIVE: We aimed to survive lambs for 6 months following the fetal repair of MMC with PMSCs. METHODS: Fetal MMC lambs were repaired with PMSCs. Lambs received either no additional treatment or postnatal bracing and physical therapy (B/PT). Motor function was assessed with the sheep locomotor rating (SLR). Lambs with an SLR of 15 at birth were survived for 6 months or until a decline in SLR less than 15, whichever came first. All lambs underwent a perimortem MRI. RESULTS: The lambs with no postnatal treatment (n = 2) had SLR declines to 7 and 13 at 29 and 65 days, respectively, and were euthanized. These lambs had a spinal angulation of 57° and 47°, respectively. The B/PT lamb (n = 1) survived for 6 months with a sustained SLR of 15 and a lumbar angulation of 42°. CONCLUSION: Postnatal physical therapy and bracing counteracted the inherent morbidity of the absent paraspinal muscles in the ovine MMC model allowing for survival and maintenance of rescued motor function of the prenatally treated lamb up to 6 months.

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.

Fetal Diagnosis and Therapy during the COVID-19 Pandemic: Guidance on Behalf of the International Fetal Medicine and Surgery Society.

The COVID-19 pandemic has stressed patients and healthcare givers alike and challenged our practice of antenatal care, including fetal diagnosis and therapy. This document aims to review relevant recent information to allow us to optimize prenatal care delivery. We discuss potential modifications to obstetric management and fetal procedures in SARS-CoV2-negative and SARS-CoV2-positive patients with fetal anomalies or disorders. Most fetal therapies are time sensitive and cannot be delayed. If personnel and resources are available, we should continue to offer procedures of proven benefit, acknowledging any fetal and maternal risks, including those to health care workers. There is, to date, minimal, unconfirmed evidence of spontaneous vertical transmission, though it may theoretically be increased with some procedures. Knowing a mother's preoperative SARS-CoV-2 status would enable us to avoid or defer certain procedures while she is contagious and to protect health care workers appropriately. Some fetal conditions may alternatively be managed neonatally. Counseling regarding fetal interventions which have a possibility of additional intra- or postoperative morbidity must be performed in the context of local resource availability. Procedures of unproven benefit should not be offered. We encourage participation in registries and trials that may help us to understand the impact of COVID-19 on pregnant women, their fetuses, and neonates.

Spinal Angulation: A Limitation of the Fetal Lamb Model of Myelomeningocele.

INTRODUCTION: The surgically induced fetal lamb model is the most commonly used large animal model of myelomeningocele (MMC) but is subject to variation due to surgical technique during defect creation. MATERIAL AND METHODS: Thirty-one fetal lambs underwent creation of the MMC defect, followed by defect repair with either an extracellular matrix (ECM) patch (n = 10) or ECM seeded with placental mesenchymal stromal cells (n = 21). Postnatal hindlimb function was assessed using the Sheep Locomotor Rating (SLR) scale. Postmortem magnetic resonance imaging of the lumbar spine was used to measure the level and degree of spinal angulation, as well as cross-sectional area of remaining vertebral bone. RESULTS: Median level of angulation was between the 2nd and 3rd lumbar vertebrae, with a median angle of 24.3 degrees (interquartile range 16.2-35.3). There was a negative correlation between angulation degree and SLR (r = -0.44, p = 0.013). Degree of angulation also negatively correlated with the normalized cross-sectional area of remaining vertebral bone (r = -0.75, p < 0.0001). DISCUSSION: Surgical creation of fetal MMC leads to varying severity of spinal angulation in the ovine model, which affects postnatal functional outcomes. Postnatal assessment of spinal angulation aids in standardization of the surgical model of fetal MMC repair.