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1.
Ann Surg ; 2024 May 29.
Article in English | MEDLINE | ID: mdl-38814074

ABSTRACT

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.

2.
Ann Surg ; 279(2): 231-239, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37916404

ABSTRACT

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.


Subject(s)
Biomedical Research , Surgeons , Humans , United States , Mentors , Faculty , Academic Medical Centers , Career Mobility , National Institutes of Health (U.S.)
3.
Ann Surg ; 278(5): 642-646, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37796749

ABSTRACT

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.


Subject(s)
Mentoring , Humans , United States , Educational Status , France
4.
Colorectal Dis ; 25(11): 2155-2159, 2023 11.
Article in English | MEDLINE | ID: mdl-37789561

ABSTRACT

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.


Subject(s)
Rectal Neoplasms , Humans , Rectal Neoplasms/surgery , Rectal Neoplasms/pathology , Rectum/surgery , Retrospective Studies , Benchmarking , Accreditation , Neoplasm Staging
5.
Fetal Diagn Ther ; 50(6): 491-500, 2023.
Article in English | MEDLINE | ID: mdl-37393899

ABSTRACT

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.


Subject(s)
Meningocele , Meningomyelocele , Spinal Dysraphism , Pregnancy , Female , Animals , Sheep , Dogs , Humans , Meningomyelocele/surgery , Spinal Dysraphism/surgery , Fetus/pathology , Prenatal Care
6.
J Surg Res ; 273: 201-210, 2022 05.
Article in English | MEDLINE | ID: mdl-35093836

ABSTRACT

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.


Subject(s)
Meningomyelocele , Mesenchymal Stem Cells , Animals , Cytokines/metabolism , Female , Gestational Age , Mesenchymal Stem Cells/metabolism , Nerve Growth Factors/metabolism , Placenta , Pregnancy , Sheep
7.
Bull World Health Organ ; 99(12): 883-891, 2021 Dec 01.
Article in English | MEDLINE | ID: mdl-34866684

ABSTRACT

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.


Subject(s)
Anesthesia , Delivery of Health Care , Child , Female , Health Planning , Humans , Nigeria , Pregnancy , Universal Health Insurance
8.
J Surg Res ; 267: 660-668, 2021 11.
Article in English | MEDLINE | ID: mdl-34273796

ABSTRACT

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.


Subject(s)
Meningomyelocele , Mesenchymal Stem Cells , Animals , Extracellular Matrix/pathology , Female , Fetus/surgery , Meningomyelocele/surgery , Mice , Placenta , Pregnancy
9.
Pediatr Surg Int ; 37(5): 659-665, 2021 May.
Article in English | MEDLINE | ID: mdl-33433663

ABSTRACT

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.


Subject(s)
Analgesics, Opioid/adverse effects , Pain, Postoperative/drug therapy , Prescription Drug Monitoring Programs , Child , Child, Preschool , Female , Humans , Male , Pediatrics , Postoperative Period , Practice Patterns, Physicians' , Prescriptions
10.
Pediatr Surg Int ; 37(5): 529-537, 2021 May.
Article in English | MEDLINE | ID: mdl-33399928

ABSTRACT

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.


Subject(s)
Child Health , Global Health , Health Services Accessibility , Surgical Procedures, Operative , Adolescent , Child , Child, Preschool , Developing Countries , Female , Health Workforce , Humans , Pregnancy , Specialties, Surgical
11.
Fetal Diagn Ther ; 48(6): 472-478, 2021.
Article in English | MEDLINE | ID: mdl-34111873

ABSTRACT

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.


Subject(s)
Cesarean Section , Meningomyelocele , Animals , Disease Models, Animal , Female , Fetus , Meningomyelocele/diagnostic imaging , Meningomyelocele/surgery , Pregnancy , Sheep , Spinal Cord/diagnostic imaging
12.
Fetal Diagn Ther ; 48(1): 43-49, 2021.
Article in English | MEDLINE | ID: mdl-33108788

ABSTRACT

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.


Subject(s)
Fetal Therapies , Hysterotomy , Amniotic Fluid , Animals , Female , Humans , Pregnancy , Primates , Uterus
13.
FASEB J ; 33(5): 5836-5849, 2019 05.
Article in English | MEDLINE | ID: mdl-30753093

ABSTRACT

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.


Subject(s)
Mesenchymal Stem Cells/cytology , Placenta/cytology , Spinal Dysraphism/therapy , Stromal Cells/cytology , Animals , Apoptosis , Cattle , Cell Line, Tumor , Coculture Techniques , Culture Media, Conditioned/chemistry , Exosomes/metabolism , Female , Galectin 1/physiology , Humans , Mesenchymal Stem Cell Transplantation , Mesoderm/cytology , Neural Tube Defects/therapy , Neurites/metabolism , Oxidative Stress , Pregnancy , Sheep , Signal Transduction , Staurosporine
14.
Fetal Diagn Ther ; 47(6): 507-513, 2020.
Article in English | MEDLINE | ID: mdl-32097922

ABSTRACT

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.


Subject(s)
Disease Models, Animal , Fetal Death/etiology , Meningomyelocele/embryology , Meningomyelocele/surgery , Sheep , Abortion, Spontaneous/epidemiology , Animals , Cesarean Section , Female , Fetal Death/prevention & control , Gestational Age , Meningomyelocele/mortality , Pregnancy , Retrospective Studies , Risk Factors , Stillbirth/epidemiology
18.
Am J Obstet Gynecol ; 218(2): 256.e1-256.e13, 2018 02.
Article in English | MEDLINE | ID: mdl-29246577

ABSTRACT

BACKGROUND: Previous reports from the Management of Myelomeningocele Study demonstrated that prenatal repair of myelomeningocele reduces hindbrain herniation and the need for cerebrospinal fluid shunting, and improves motor function in children with myelomeningocele. The trial was stopped for efficacy after 183 patients were randomized, but 30-month outcomes were only available at the time of initial publication in 134 mother-child dyads. Data from the complete cohort for the 30-month outcomes are presented here. Maternal and 12-month neurodevelopmental outcomes for the full cohort were reported previously. OBJECTIVE: The purpose of this study is to report the 30-month outcomes for the full cohort of patients randomized to either prenatal or postnatal repair of myelomeningocele in the original Management of Myelomeningocele Study. STUDY DESIGN: Eligible women were randomly assigned to undergo standard postnatal repair or prenatal repair <26 weeks gestation. We evaluated a composite of mental development and motor function outcome at 30 months for all enrolled patients as well as independent ambulation and the Bayley Scales of Infant Development, Second Edition. We assessed whether there was a differential effect of prenatal surgery in subgroups defined by: fetal leg movements, ventricle size, presence of hindbrain herniation, gender, and location of the myelomeningocele lesion. Within the prenatal surgery group only, we evaluated these and other baseline parameters as predictors of 30-month motor and cognitive outcomes. We evaluated whether presence or absence of a shunt at 1 year was associated with 30-month motor outcomes. RESULTS: The data for the full cohort of 183 patients corroborate the original findings of Management of Myelomeningocele Study, confirming that prenatal repair improves the primary outcome composite score of mental development and motor function (199.4 ± 80.5 vs 166.7 ± 76.7, P = .004). Prenatal surgery also resulted in improvement in the secondary outcomes of independent ambulation (44.8% vs 23.9%, P = .004), WeeFIM self-care score (20.8 vs 19.0, P = .006), functional level at least 2 better than anatomic level (26.4% vs 11.4%, P = .02), and mean Bayley Scales of Infant Development, Second Edition, psychomotor development index (17.3% vs 15.1%, P = .03), but does not affect cognitive development at 30 months. On subgroup analysis, there was a nominally significant interaction between gender and surgery, with boys demonstrating better improvement in functional level and psychomotor development index. For patients receiving prenatal surgery, the presence of in utero ankle, knee, and hip movement, absence of a sac over the lesion and a myelomeningocele lesion of ≤L3 were significantly associated with independent ambulation. Postnatal motor function showed no correlation with either prenatal ventricular size or postnatal shunt placement. CONCLUSION: The full cohort data of 30-month cognitive development and motor function outcomes validate in utero surgical repair as an effective treatment for fetuses with myelomeningocele. Current data suggest that outcomes related to the need for shunting should be counseled separately from the outcomes related to distal neurologic functioning.


Subject(s)
Fetal Therapies , Meningomyelocele/surgery , Neurodevelopmental Disorders/prevention & control , Adult , Child Development , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Meningomyelocele/complications , Meningomyelocele/diagnosis , Neurodevelopmental Disorders/etiology , Pregnancy , Prospective Studies , Single-Blind Method , Treatment Outcome
19.
World J Surg ; 42(10): 3432-3442, 2018 10.
Article in English | MEDLINE | ID: mdl-29619512

ABSTRACT

BACKGROUND: Mongolia is a country characterized by its vast distances and extreme climate. An underdeveloped medical transport infrastructure makes patient transfer from outlying regions dangerous. Providing pediatric surgical care locally is crucial to improve the lives of children in the countryside. This is the first structured assessment of nationwide pediatric surgical capacity. METHODS: Operation rates were calculated using data from the Mongolian Center for Health Development and population data from the Mongolian Statistical Information Service. The Pediatric Personnel, Infrastructure, Procedures, Equipment, and Supplies (PediPIPES) survey tool was used to collect data at all survey sites. Descriptive data analyses were completed using Excel. Studies of association were completed using Stata. All reported percentages are of the hospitals outside of the capital (n = 21). RESULTS: All provincial hospitals have general surgeons; seven (33.3%) of them have pediatric surgeon(s). One facility has no anesthesiologist. All facilities perform basic procedures and provide anesthesia. Four (19%) can treat common congenital anomalies. All facilities have basic operating room equipment. Nine hospitals do not have pulse oximetry available. Twelve hospitals do not have pediatric surgical instruments always available. Pediatric supplies are lacking. CONCLUSIONS: Provincial hospitals in Mongolia can perform basic procedures. However, essential pediatric supplies are lacking. Consequently, certain life-saving procedures are not available to children outside of the capital. Only a few improvements would be amendable to low-cost process improvement adjustment, and the majority of needs require resource additions. Procedure, equipment, and supply availability should be further explored to develop a comprehensive nationwide pediatric surgical program.


Subject(s)
Health Resources/supply & distribution , Health Services Accessibility/statistics & numerical data , Pediatrics , Specialties, Surgical , Surgical Procedures, Operative/statistics & numerical data , Adolescent , Child , Child, Preschool , Cross-Sectional Studies , Female , Health Care Surveys , Humans , Infant , Infant, Newborn , Male , Mongolia , Rural Health Services/supply & distribution
20.
BMC Fam Pract ; 19(1): 64, 2018 05 16.
Article in English | MEDLINE | ID: mdl-29769017

ABSTRACT

BACKGROUND: Over one million asylum seekers were registered in Germany in 2016, most from Syria and Afghanistan. The Refugee Convention guarantees access to healthcare, however delivery mechanisms remain heterogeneous. There is an urgent need for more data describing the health conditions of asylum seekers to guide best practices for healthcare delivery. In this study, we describe the state of health of asylum seekers presenting to a multi-specialty primary care refugee clinic. METHODS: Demographic and medical diagnosis data were extracted from the electronic medical records of patients seen at the ambulatory refugee clinic in Dresden, Germany between 15 September 2015 and 31 December 2016. Data were de-identified and analyzed using Stata version 14.0. RESULTS: Two-thousand-seven-hundred and fifty-three individual patients were seen in the clinic. Of these, 2232 (81.1%) were insured by the state indicating arrival within the last 3 months. The median age was 25, interquartile range 16-34. Only 786 (28.6%) were female, while 1967 (71.5%) were male. The most frequent diagnoses were respiratory (17.4%), followed by miscellaneous symptoms and otherwise not classified ailments (R series, 14.1%), infection (10.8%), musculoskeletal or connective tissue (9.3%), gastrointestinal (6.8%), injury (5.9%), and mental or behavioral (5.1%) categories. CONCLUSIONS: This study illustrates the diverse medical conditions that affect the asylum seeker population. Asylum seekers in our study group did not have a high burden of communicable diseases, however several warranted additional screening and treatment, including for tuberculosis and scabies. Respiratory illnesses were more common amongst newly arrived refugees. Trauma-related mental health disorders comprised half of mental health diagnoses.


Subject(s)
Health Status , Refugees , Adolescent , Adult , Afghanistan/ethnology , Age Distribution , Aged , Aged, 80 and over , Ambulatory Care Facilities , Child , Child, Preschool , Communicable Diseases/ethnology , Electronic Health Records , Female , Gastrointestinal Diseases/ethnology , Germany/epidemiology , Humans , Infant , Male , Mental Disorders/ethnology , Middle Aged , Musculoskeletal Diseases/ethnology , Pregnancy , Syria/ethnology , Young Adult
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