Publications by authors named "Daniel F Labuz"
Purpose: We sought to determine the feasibility and routing kinetics of transamniotic fetal delivery of secretory immunoglobulin-A (SIgA), in a rodent model.
Methods: Fetuses (n = 94) from seven time-dated pregnant dams received intra-amniotic injections on gestational day 17 (E17, term = E21-22) of either saline (n = 15) or a solution of 1 mg/mL of ≥95% homogeneous human SIgA (n = 79). Animals were euthanized daily at E18-E21 for quantification of the IgA component by ELISA at gestational membranes, placenta, and select fetal anatomical sites against saline controls procured at term.
Article Synopsis
- - The study examined how having guidelines for chemoprophylaxis affects the incidence of venous thromboembolism (VTE) in pediatric trauma patients, given the lack of previous data in this area.
- - Researchers reviewed data from 45,202 injured children across 10 trauma centers over nine years, comparing those with and without chemoprophylaxis guidelines.
- - While the presence of guidelines correlated with lower VTE rates, the actual impact was confounded by patient risk factors; many who developed VTE were not indicated for treatment based on these guidelines.
Hematopoietic stem cell (HSC)-based gene therapy has already reached clinical reality in a few applications. Fetal administration of genetically modified HSCs has only been feasible to date through invasive and morbid methods. It has been recently shown that native donor HSCs can reach the fetal circulation and bone marrow after simple delivery into the amniotic fluid, at least in a syngeneic healthy model.
View Article and Find Full Text PDFPurpose: Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) has been shown experimentally to reverse some of the effects of intrauterine growth restriction (IUGR), apparently by attenuating placental inflammation. Neurodevelopmental deficits driven by neuroinflammation are major complications of IUGR. We sought to determine whether MSC-based TRASCET also mitigates inflammation in the fetal brain.
View Article and Find Full Text PDFPurpose: Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) has been shown to impact pulmonary vascular development and remodeling in experimental congenital diaphragmatic hernia (CDH), with secondary structural cardiac effects. We sought to determine whether TRASCET has any functional impact on term fetal pulmonary hemodynamics in the nitrofen model.
Methods: Time-dated pregnant rat dams (n = 13) received nitrofen on gestational day 9 (E9) to induce fetal CDH.
Background: This prospective observational cohort study evaluates risk-stratified venous thromboembolism (VTE) screening in injured children. While the reported incidence of VTE is 6% to 10% among critically injured children, there is no standard for screening. Venous thromboembolism may have long-term sequelae in children, including postthrombotic syndrome.
View Article and Find Full Text PDFPurpose: The transamniotic route was recently discovered as a minimally invasive means of fetal immunoglobulin administration, however by unclear mechanisms. We sought to examine IgG routing after intra-amniotic delivery.
Methods: Sprague-Dawley fetuses (n = 78) received intra-amniotic injections of 15 mg/mL of human IgG on gestational-day 18 (E18; term=21 and 22 days).
Background: We sought to determine the pathway through which syngeneic hematopoietic stem cells (HSCs) delivered into the amniotic fluid can reach the fetal circulation.
Methods: Lewis rat fetuses were divided in two groups based on the content of intra-amniotic injections performed on gestational day 17 (E17; term=E21-22): either a suspension of luciferase-labeled syngeneic HSCs (n = 137), or acellular luciferase (n = 44). Samples from placenta, chorion, amnion, amniotic fluid, umbilical cord, and 8 fetal sites were procured at 5 daily time points thereafter until term for analysis.
Article Synopsis
- Researchers explored using mesenchymal stem cell-based transamniotic therapy to treat intrauterine growth restriction (IUGR) in a study involving hypoxic pregnant rats.
- Four groups were created: untreated, sham (saline), and two MSC treatment groups — one with unprimed and one with primed stem cells.
- Results showed that while all hypoxic groups had reduced fetal weights, the primed MSC group normalized placental efficiency and potentially reversed some growth restriction effects, indicating promise for future treatments.
Reoperation to correct unsuccessful vascular ring and vascular decompression surgery.
J Thorac Cardiovasc Surg
July 2022
Objective: Although most children do well after operations to relieve vascular compression of the esophagus and airway, many will have persistent/recurrent symptoms. We review our surgical experience using a customized approach to correct various etiologies of failure after vascular ring/decompression surgery.
Methods: Our institutional database identified children who underwent reoperation for persistent/recurrent symptoms after vascular ring or aberrant arterial decompression surgery between January 2014 and December 2019.
Purpose: We sought to determine whether the amniotic cavity/fluid could be an attainable route of administration of therapeutic antibodies to the fetus/neonate.
Methods: Time-dated pregnant dams (n = 9) received volume-matched intra-amniotic injections of either saline (n = 29), or different concentrations of a human IgG that lacked homology with rodents: 5 mg/mL (n = 28); 10 mg/mL (n = 28); or 15 mg/mL (n = 24). At term, the presence of the IgG was quantified by ELISA in the serum, bone marrow, spleen, thymus, and brain of all neonates, and in the maternal serum.
Article Synopsis
- * A multicenter study involving 10 institutions investigated the accuracy of trauma registries and assessed an established VTE prediction algorithm using multiple patient variables to determine its effectiveness.
- * Out of 52,524 pediatric trauma patients, initial VTE cases were overreported; after correction, the algorithm still effectively identified VTE occurrences, indicating high sensitivity and specificity, while revealing significant issues with central line-associated VTEs and underreported prophylaxis rates.
Introduction: Several fetal therapies involve repeated amniotic fluid intervention. We hypothesize that a minimally invasive approach can be used to safely implant an intrauterine catheter infusion system in a fetal ovine model for chronic use during pregnancy.
Method: Five pregnant sheep underwent operation between gestational days 110 and 115 (term 145 days).
Purpose: We examined select pulmonary effects and donor cell kinetics after transamniotic stem cell therapy (TRASCET) in a model of congenital diaphragmatic hernia (CDH).
Methods: Pregnant dams (n = 58) received nitrofen on gestational day 9.5 (E9) to induce fetal CDH.
Background/purpose: In utero administration of hematopoietic stem cells (HSCs) has a variety of actual or potential clinical applications but is hindered by invasive, morbid administration techniques. We sought to determine whether donor HSCs could reach the fetal circulation after simple intra-amniotic delivery in a syngeneic rat model of transamniotic stem cell therapy (TRASCET).
Methods: Pregnant Lewis rat dams underwent volume-matched intra-amniotic injections in all fetuses (n = 90) on gestational day 17 (E17; term=E21-22) of a suspension of commercially available syngeneic Lewis rat HSCs labeled with luciferase (n = 37 fetuses) or an acellular suspension of recombinant luciferase (n = 53).
Background/purpose: We examined whether engineered overexpression of fibroblast growth factor-2 (Fgf2) in donor mesenchymal stem cells (MSCs) could enhance spina bifida coverage induced by transamniotic stem cell therapy (TRASCET).
Methods: Pregnant Sprague-Dawley dams (n = 24) exposed to retinoic acid for induction of fetal spina bifida were divided in three groups. An untreated group had no further manipulations.
Background/purpose: We sought to test select properties of a novel, expandable bioadhesive composite that allows for enhanced adhesion control in liquid environments.
Methods: Rabbit fetuses (n = 23) underwent surgical creation of spina bifida on gestational day 22-25 (term 32-33 days). Defects were immediately covered with a two-component tough adhesive consisting of a hydrogel made of a double network of ionically crosslinked alginate and covalently crosslinked polyacrylamide linked to a bridging chitosan polymer adhesive.
Gastroschisis is a congenital abdominal wall defect that, when simple, has excellent overall outcomes. However, morbidity increases with prematurity. A staged approach to closure is often needed until the infant can tolerate definitive repair.
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