Kenneth W Liechty

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• Bolouvi, E. H., Seckeler, M. D., Price, A., Morgan, W., Lightwine, B., & Liechty, K. W. (2025). Management of severe left main bronchomalacia in an infant with a balloon expandable bare metal coronary stent: a case report. Journal of Pediatric Surgery Case Reports, 120(Issue). doi:10.1016/j.epsc.2025.103042
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  Introduction: Managing bronchomalacia in infants represents a significant challenge. Surgical strategies such as aortopexy and tracheopexy have variable outcomes in distal airway disease. Stent placement is typically reserved as a last resort in selected cases. Case presentation: A 4-month-old ex-34-weeker infant status-post neonatal repair of a large omphalocele was re-intubated six weeks post-operatively for severe respiratory distress. Despite escalating positive-end expiratory pressure, bronchodilators, and airway clearance, the respiratory function continued to decline. Bronchoscopy showed severe left main bronchomalacia and bronchial stenosis, confirmed by chest computerized tomography (CT). There was near complete occlusion of the left main bronchus, but with patent distal airway. A 4.5 mm × 15 mm bare metal coronary stent (Resolute Onyx Frontier) was placed in the left main bronchus under fluoroscopic and bronchoscopic guidance. This led to an immediate improvement in lung mechanics, with subsequent extubation. The stent was electively removed after 11 weeks. However, re-occlusion occurred within 24 hours due to airway compression, which was managed with the placement of a second stent (5 mm × 15 mm). The symptoms resolved completely, and the patient was discharged home at the age of 10 months. He was subsequently managed at a different hospital. At the age of 14 months the stent was removed. Shortly after the removal, he had a recurrence of the left lung collapse and a respiratory infection requiring extracorporeal membrane oxygenation (ECMO). An 8 mm × 20 mm stent was then placed to recruit the left lung and allow ECMO decannulation. He remains with the stent in place. Conclusion: Bare metal coronary stents appear to be an effective temporizing management option for infants with severe bronchomalacia who fail standard non-operative measures, allowing time for the airway to become more rigid.
• Chenchar, A., Pereira, V. M., Apte, A., Lyttle, B. D., Vaughn, A. E., Lehmann, T., Bardill, J. R., Zgheib, C., Liechty, K. W., Roballo, K. C., Zhang, Z., Alexander, B. M., & Nair, S. (2025). Targeting Cathepsin K to Accelerate Diabetic Wound Healing. ACS Pharmacology and Translational Science, 8(Issue 7). doi:10.1021/acsptsci.5c00295
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  Objective: Elevated protease activity impairs wound healing. Cathepsin K is a cysteine protease with potent collagenolytic and elastolytic activity. This study examined the effects of odanacatib, a cathepsin K inhibitor, on wound healing in a diabetic porcine model. Additionally, it assessed whether the genetic deletion of cathepsin K improves wound healing in diabetic mice. Approach: Three cohorts of three-month-old female Yorkshire pigs (eight to ten pigs per cohort) were rendered diabetic via intravenous injections of streptozotocin (STZ, 75 mg/kg). After 4 weeks, ten full-thickness (∼300 μm) excisional skin wounds, each measuring one square inch, were created on the dorsal surface of each animal. The wounds were treated with either vehicle or odanacatib (30 or 300 ng/mm2) via intradermal injection on days 0, 3, 7, and 14. For mouse studies, diabetes was induced in cathepsin K knockout (Ctsk-/-) and wild-type C57BL/6 mice via STZ injections, and a single full-thickness excisional wound was created on each mouse. The wounds were photographed and assessed on days 0, 7, 14, 21, and daily until complete closure. Wound healing progression was evaluated by measuring wound closure rates, CD31 expression, and histology. An in vitro scratch assay was utilized to assess the effect of odanacatib on the migration of cultured skin fibroblasts and keratinocytes under high-glucose conditions. Results: Odanacatib treatment significantly accelerated wound closure in diabetic pigs, promoting epithelialization and ECM stability. Similarly, diabetic Ctsk-/- mice exhibited improved healing compared to wild-type controls. In vitro, odanacatib increased the migration of fibroblasts and keratinocytes under hyperglycemic conditions. Innovation and Conclusion: This study is the first to demonstrate that inhibiting cathepsin K, either genetically or pharmacologically, improves diabetic wound healing. These findings position cathepsin K as a promising therapeutic target for the treatment of chronic wounds.
• Credille, C., Eason, C. R., Evans, L. L., Bothwell, S., Gien, J., Vaughn, A. E., Kinsella, J. P., Varma, P., Liechty, K. W., & Christopher Derderian, S. (2025). Bleeding Complications between Bivalirudin and Heparin for Extracorporeal Membrane Oxygenation in Neonates with Congenital Diaphragmatic Hernia. Fetal Diagnosis and Therapy, 52(Issue 2). doi:10.1159/000542760
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  Introduction: Neonates with congenital diaphragmatic hernia (CDH) who undergo repair while on extracorporeal membrane oxygenation (ECMO) are at risk of developing post-operative bleeding complications. Balanced anticoagulation is critical to maintain ECMO flow and avoid bleeding. Heparin has historically been our first-line anticoagulant; however, recently, we transitioned to bivalirudin, a direct thrombin inhibitor. The objective of this pilot study was to compare post-operative surgical bleeding complications between the two groups. Methods: We performed a single center retrospective cohort study of patients who underwent CDH repair while on ECMO between 2008 and 2023. Neonates were stratified based on the type of anticoagulant initiated after CDH repair. Outcomes included bleeding requiring surgical re-operation, intracranial hemorrhage, volume of blood products transfused, number of circuit changes, days on ECMO, and overall survival. Results: Among 62 neonates with CDH who underwent repair on ECMO, 44 (71%) were managed post-CDH repair with heparin and 18 (29%) with bivalirudin. One (5.6%) neonate managed with bivalirudin underwent re-operation following CDH repair for a bleeding complication compared to 17 (38.6%) managed with heparin (p = 0.022). In addition, the bivalirudin cohort utilized half of the total blood product volume compared to the heparin cohort (p = 0.020). Despite these benefits, there were no significant differences between groups for incidence of intracranial hemorrhage, number of circuit changes, days on ECMO, and overall survival. Conclusion: Anticoagulation with bivalirudin in neonates who underwent CDH repair while on ECMO was associated with decreased surgical bleeding complications and less total blood product transfused. This pilot analysis is the first to compare heparin to bivalirudin and stresses the importance of a multicenter study.
• Elajaili, H., Lyttle, B. D., Lewis, C. V., Bardill, J. R., Dee, N., Seal, S., Nozik, E. S., Liechty, K. W., & Zgheib, C. (2025). Increased ROS and Persistent Pro-Inflammatory Responses in a Diabetic Wound Healing Model (db/db): Implications for Delayed Wound Healing. International Journal of Molecular Sciences, 26(Issue 10). doi:10.3390/ijms26104884
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  Diabetes and its complications, including impaired wound healing, present a critical clinical challenge and burden for the U.S. healthcare system, with costs of over USD 13 billion annually. Hyperglycemia and chronic inflammation in diabetic wounds increase reactive oxygen species (ROS) production, inducing oxidative stress and perpetuating inflammation, which delays healing. This study investigates inflammation, oxidative stress, and the roles of cellular populations in a diabetic wound healing mouse model (db/db). Given that diabetes leads to persistent inflammation and impaired fibroblast function, we also examined how diabetes influences superoxide production in dermal fibroblasts. Blood, dermal fibroblasts, and wound tissue were collected from 12-week-old female diabetic (Db) and heterozygous (Hz) mice. Electron paramagnetic resonance (EPR) spectroscopy revealed higher superoxide levels in diabetic blood, dermal fibroblasts, and wounds compared to controls. In diabetic wounds, immunohistochemistry and flow cytometry showed increased leukocyte infiltration and reduced macrophage presence, with a higher proportion of pro-inflammatory Ly6Chi macrophages. These results suggest that elevated superoxide production and persistent inflammation contribute to impaired fibroblast function and delayed wound healing in diabetes. By identifying the contributions of ROS and Ly6Chi macrophages to oxidative stress and chronic inflammation, this study offers insights into therapeutic strategies. These findings highlight the importance of addressing systemic oxidative stress alongside localized inflammation to improve wound healing outcomes in diabetic patients and advance diabetic wound care strategies.
• Apte, A., Bardill, J. R., Canchis, J., Skopp, S. M., Fauser, T., Lyttle, B., Vaughn, A. E., Seal, S., Jackson, D. M., Liechty, K. W., & Zgheib, C. (2024). Targeting Inflammation and Oxidative Stress to Improve Outcomes in a TNBS Murine Crohn's Colitis Model. Nanomaterials (Basel, Switzerland), 14(10).
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  Inflammation and oxidative stress are implicated in the pathogenesis of Crohn's disease. Cerium oxide nanoparticle (CNP) conjugated to microRNA 146a (miR146a) (CNP-miR146a) is a novel compound with anti-inflammatory and antioxidative properties. We hypothesized that local administration of CNP-miR146a would improve colitis in a 2,4,6-Trinitrobenzenesulfonic acid (TNBS) mouse model for Crohn's disease by decreasing colonic inflammation. Balb/c mice were instilled with TNBS enemas to induce colitis. Two days later, the mice received cellulose gel enema, cellulose gel with CNP-miR146a enema, or no treatment. Control mice received initial enemas of 50% ethanol and PBS enemas on day two. The mice were monitored daily for weight loss and clinical disease activity. The mice were euthanized on days two or five to evaluate their miR146a expression, inflammation on histology, and colonic IL-6 and TNF gene expressions and protein concentrations. CNP-miR146a enema successfully increased colonic miR146a expression at 12 h following delivery. At the end of five days from TNBS instillation, the mice treated with CNP-miR146a demonstrated reduced weight loss, improved inflammation scores on histology, and reduced gene expressions and protein concentrations of IL-6 and TNF. The local delivery of CNP-miR146a in a TNBS mouse model of acute Crohn's colitis dramatically decreased inflammatory signaling, resulting in improved clinical disease.
• Apte, A., Fauser, T., Carson, Q., Liechty, K. W., Simpson, L. N., & Avellino, A. M. (2024). In utero Diagnosis of Spinal Dermal Sinus. Fetal diagnosis and therapy, 51(3), 235-242.
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  Congenital dermal sinus (CDS) is an open neural tube defect (NTD) that occurs in 1 in 2,500 births a year and often goes undetected until patients present with complications like infection and neurological deficits. Early diagnosis and repair of CDS may prevent formation of these complications. In utero diagnosis of these lesions may improve long-term outcomes by enabling referral to specialty services and planned postnatal repair; however, only 2 such cases have been reported in the literature. We present a third case of in utero diagnosis of CDS with a description and discussion of findings from surgical exploration and pathology.
• Gallagher, L. T., Bardill, J., Sucharov, C. C., Wright, C. J., Karimpour-Fard, A., Zarate, M., Breckenfelder, C., Liechty, K. W., & Derderian, S. C. (2024). Dysregulation of miRNA-mRNA expression in fetal growth restriction in a caloric restricted mouse model. Scientific reports, 14(1), 5579.
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  Fetal growth restriction (FGR) is associated with aberrant placentation and accounts for a significant proportion of perinatal deaths. microRNAs have been shown to be dysregulated in FGR. The purpose of this study was to determine microRNA-regulated molecular pathways altered using a caloric restricted mouse model of FGR. Pregnant mice were subjected to a 50% caloric restricted diet beginning at E9. At E18.5, RNA sequencing of placental tissue was performed to identify differences in gene expression between caloric restricted and control placentas. Significant differences in gene expression between caloric restricted and control placentas were observed in 228 of the 1546 (14.7%) microRNAs. Functional analysis of microRNA-mRNA interactions demonstrated enrichment of several biological pathways with oxidative stress, apoptosis, and autophagy pathways upregulated and angiogenesis and signal transduction pathways downregulated. Ingenuity pathway analysis also suggested that ID1 signaling, a pathway integral for trophoblast differentiation, is also dysregulated in caloric restricted placentas. Thus, a maternal caloric restriction mouse model of FGR results in aberrant microRNA-regulated molecular pathways associated with angiogenesis, oxidative stress, signal transduction, apoptosis, and cell differentiation. As several of these pathways are dysregulated in human FGR, our findings suggest that this model may provide an excellent means to study placental microRNA derangements seen in FGR.
• Lyttle, B. D., Derderian, S. C., Neuberger, I., Behrendt, N. J., Pickett-Nairne, K., Francom, C. R., Liechty, K. W., & Meyers, M. L. (2024). Comparison of best landmarks for calculating fetal jaw measurements by ultrasound and MRI in micrognathia. Pediatric radiology, 54(11), 1850-1861.
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  Micrognathia can be diagnosed in utero with ultrasound by measuring the jaw index and/or inferior facial angle, though it can be challenging due to fetal positioning. The jaw index can be measured with magnetic resonance imaging (MRI) using the masseter muscle, but indistinct margins can lead to inaccuracy; the easily visualized posterior teeth buds may be a better landmark.
• Vaughn, A. E., Lyttle, B. D., Louiselle, A. E., Cooper, E., Niemiec, S. M., Phillips, R., Hilton, S. A., Kinsella, J. P., Gien, J., Derderian, S. C., & Liechty, K. W. (2024). Muscle Flap Technique Safe for On-ECMO Congenital Diaphragmatic Hernia Repair. Journal of pediatric surgery, 59(5), 962-968.
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  Prosthetic patches (patch) and muscle flaps (flap) are techniques used for repair of congenital diaphragmatic hernia (CDH) with a large defect unamenable to primary closure. We hypothesized that the flap technique for CDH repair while on extra-corporeal membrane oxygenation (on-ECMO) would have decreased bleeding complications compared to patch due to the hemostatic advantage of native tissue.
• Apte, A., Liechty, K. W., & Zgheib, C. (2023). Immunomodulatory biomaterials on chemokine signaling in wound healing. Frontiers in pharmacology, 14, 1084948.
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  Normal wound healing occurs through a careful orchestration of cytokine and chemokine signaling in response to injury. Chemokines are a small family of chemotactic cytokines that are secreted by immune cells in response to injury and are primarily responsible for recruiting appropriate immune cell types to injured tissue at the appropriate time. Dysregulation of chemokine signaling is suspected to contribute to delayed wound healing and chronic wounds in diseased states. Various biomaterials are being used in the development of new therapeutics for wound healing and our understanding of their effects on chemokine signaling is limited. It has been shown that modifications to the physiochemical properties of biomaterials can affect the body's immune reaction. Studying these effects on chemokine expression by various tissues and cell type can help us develop novel biomaterial therapies. In this review, we summarize the current research available on both natural and synthetic biomaterials and their effects on chemokine signaling in wound healing. In our investigation, we conclude that our knowledge of chemokines is still limited and that many in fact share both pro-inflammatory and anti-inflammatory properties. The predominance of either a pro-inflammatory or anti-inflammatory profile is mostly likely dependent on timing after injury and exposure to the biomaterial. More research is needed to better understand the interaction and contribution of biomaterials to chemokine activity in wound healing and their immunomodulatory effects.
• Gallagher, L. T., Lyttle, B. D., Meyers, M. L., Gien, J., Zaretsky, M. V., Galan, H. L., Behrendt, N., Liechty, K. W., & Derderian, S. C. (2023).

  Fetal lung volumes measured by MRI predict pulmonary morbidity among infants with giant omphaloceles

  . Prenatal Diagnosis, 43(12), 1514-1519. doi:10.1002/pd.6449
• Gallagher, L. T., Wright, C. J., Lehmann, T., Khailova, L., Zarate, M., Lyttle, B. D., Liechty, K. W., & Derderian, S. C. (2023). Angiogenic and Inflammatory microRNA Regulation in a Mouse Model of Fetal Growth Restriction. The Journal of surgical research, 292, 234-238.
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  Fetal growth restriction (FGR) is associated with impaired angiogenesis and chronic inflammation. MicroRNAs (miRs) are short noncoding RNAs that regulate gene expression at the post-transcriptional level by targeting messenger RNA (mRNA) for degradation or by suppressing translation. We hypothesize that dysregulation of miR-15b, an antiangiogenic miR, and miR-146a, an anti-inflammatory miR, are associated with the FGR's pathogenesis.
• Lyttle, B. D., Vaughn, A. E., Bardill, J. R., Apte, A., Gallagher, L. T., Zgheib, C., & Liechty, K. W. (2023). Effects of microRNAs on angiogenesis in diabetic wounds. Frontiers in medicine, 10, 1140979.
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  Diabetes mellitus is a morbid condition affecting a growing number of the world population, and approximately one third of diabetic patients are afflicted with diabetic foot ulcers (DFU), which are chronic non-healing wounds that frequently progress to require amputation. The treatments currently used for DFU focus on reducing pressure on the wound, staving off infection, and maintaining a moist environment, but the impaired wound healing that occurs in diabetes is a constant obstacle that must be faced. Aberrant angiogenesis is a major contributor to poor wound healing in diabetes and surgical intervention is often necessary to establish peripheral blood flow necessary for healing wounds. Over recent years, microRNAs (miRNAs) have been implicated in the dysregulation of angiogenesis in multiple pathologies including diabetes. This review explores the pathways of angiogenesis that become dysregulated in diabetes, focusing on miRNAs that have been identified and the mechanisms by which they affect angiogenesis.
• Peddibhotla, S., Caples, K., Mehta, A., Chen, Q. Y., Hu, J., Idlett-Ali, S., Zhang, L., Zgheib, C., Xu, J., Liechty, K. W., & Malany, S. (2023). Triazolothiadiazine derivative positively modulates CXCR4 signaling and improves diabetic wound healing. Biochemical pharmacology, 216, 115764.
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  Development of specific therapies that target and accelerate diabetic wound repair is an urgent need to alleviate pain and suffering and the huge socioeconomic burden of this debilitating disease. C-X-C Motif Chemokine Ligand 12 (CXCL12) also know an stromal cell-derived factor 1α (SDF-1α) is a chemokine that binds the CXC chemokine receptor type 4 (CXCR4) and activates downstream signaling resulting in recruitment of hematopoietic cells to locations of tissue injury and promotes tissue repair. In diabetes, low expression of CXCL12 correlates with impaired wound healing. Activation of CXCR4 receptor signaling with agonists or positive allosteric modulators (PAMs) provides a potential for small molecule therapeutic discovery and development. We recently reported high throughput screening and identification of the CXCR4 partial agonist UCUF-728, characterization of in vitro activity and reduced wound closure time in diabetic mice at 100 μM as a proof-of-concept study. We report here, the discovery of a second chemical scaffold demonstrating increased agonist potency and represented by thiadiazine derivative, UCUF-965. UCUF-965 is a potent partial agonist of β-arrestin recruitment in CXCR4 receptor overexpressing cell line. Furthermore, UCUF-965 potentiates the CXCL12 maximal response in cAMP signaling pathway, activates CXCL12 stimulated migration in lymphoblast cells and modulates the levels of specific microRNA involved in the complex wound repair process, specifically in mouse fibroblasts. Our results indicate that UCUF-965 acts as a PAM agonist of the CXCR4 receptor. Furthermore, UCUF-965 enhanced angiogenesis markers and reduced wound healing time by 36% at 10.0 μM in diabetic mice models compared to untreated control.
• Vaughn, A. E., Lehmann, T., Sul, C., Wallbank, A. M., Lyttle, B. D., Bardill, J., Burns, N., Apte, A., Nozik, E. S., Smith, B., Vohwinkel, C. U., Zgheib, C., & Liechty, K. W. (2023). CNP-miR146a Decreases Inflammation in Murine Acute Infectious Lung Injury. Pharmaceutics, 15(9).
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  Acute respiratory distress syndrome (ARDS) has approximately 40% in-hospital mortality, and treatment is limited to supportive care. Pneumonia is the underlying etiology in many cases with unrestrained inflammation central to the pathophysiology. We have previously shown that CNP-miR146a, a radical scavenging cerium oxide nanoparticle (CNP) conjugated to the anti-inflammatory microRNA(miR)-146a, reduces bleomycin- and endotoxin-induced acute lung injury (ALI) by decreasing inflammation. We therefore hypothesized that CNP-miR146a would decrease inflammation in murine infectious ALI. Mice were injured with intratracheal (IT) MRSA or saline followed by treatment with IT CNP-miR146a or saline control. Twenty-four hours post-infection, bronchoalveolar lavage fluid (BALF) and whole lungs were analyzed for various markers of inflammation. Compared to controls, MRSA infection significantly increased proinflammatory gene expression (IL-6, IL-8, TNFα, IL-1β; < 0.05), BALF proinflammatory cytokines (IL-6, IL-8, TNFα, IL-1β; < 0.01), and inflammatory cell infiltrate ( = 0.03). CNP-miR146a treatment significantly decreased proinflammatory gene expression (IL-6, IL-8, TNFα, IL-1β; < 0.05), bronchoalveolar proinflammatory protein leak (IL-6, IL-8, TNFα; < 0.05), and inflammatory infiltrate ( = 0.01). CNP-miR146a decreases inflammation and improves alveolar-capillary barrier integrity in the MRSA-infected lung and has significant promise as a potential therapeutic for ARDS.
• Vaughn, A. E., Louiselle, A. E., Tong, S., Niemiec, S. M., Ahmad, S., Zaretsky, M., Galan, H. L., Behrendt, N., Wilkinson, C. C., O'Neill, B., Handler, M., Derderian, S. C., Mirsky, D. M., & Liechty, K. W. (2023). Early outcomes of a myofascial repair technique for fetal myelomeningocele. Journal of pediatric surgery, 58(1), 20-26.
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  Fetal repair of myelomeningocele (MMC) and myeloschisis leads to improved neurologic outcomes compared to postnatal repair, but the effects of modifications in closure techniques have not been extensively studied. Previous work has suggested that a watertight repair is requisite for improvement in hindbrain herniation (HBH) and to decrease postnatal hydrocephalus (HCP). Our institution adopted the myofascial closure technique for open fetal MMC repair in July 2019, which we hypothesized would result in decreased need for patch closure, improved HBH, and decreased rate of surgically-treated HCP.
• Vaughn, A. E., Lyttle, B. D., Tran, W., Derderian, S. C., Liechty, K. W., & Gien, J. (2023). Surgical Necrotizing Enterocolitis - Can We Predict the Need for Gastrostomy Tube Placement?. The Journal of surgical research, 295, 168-174.
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  Necrotizing enterocolitis (NEC) is a significant cause of morbidity and mortality among extremely premature infants. Approximately 50% of cases progress to surgery, frequently resulting in resection of necrotic bowel and ostomy creation. Premature neonates are at risk for bronchopulmonary dysplasia and feeding failure; surgery in these patients is higher risk. We evaluated the incidence of gastrostomy tube (GT) placement after ostomy reversal in surgical NEC to define a subset of patients who would benefit from concurrent ostomy reversal and GT placement.
• Wallbank, A. M., Vaughn, A. E., Niemiec, S., Bilodeaux, J., Lehmann, T., Knudsen, L., Kolanthai, E., Seal, S., Zgheib, C., Nozik, E., Liechty, K. W., & Smith, B. J. (2023). CNP-miR146a improves outcomes in a two-hit acute- and ventilator-induced lung injury model. Nanomedicine : nanotechnology, biology, and medicine, 50, 102679.
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  Acute respiratory distress syndrome (ARDS) has high mortality (~40 %) and requires the lifesaving intervention of mechanical ventilation. A variety of systemic inflammatory insults can progress to ARDS, and the inflamed and injured lung is susceptible to ventilator-induced lung injury (VILI). Strategies to mitigate the inflammatory response while restoring pulmonary function are limited, thus we sought to determine if treatment with CNP-miR146a, a conjugate of novel free radical scavenging cerium oxide nanoparticles (CNP) to the anti-inflammatory microRNA (miR)-146a, would protect murine lungs from acute lung injury (ALI) induced with intratracheal endotoxin and subsequent VILI. Lung injury severity and treatment efficacy were evaluated via lung mechanical function, relative gene expression of inflammatory biomarkers, and lung morphometry (stereology). CNP-miR146a reduced the severity of ALI and slowed the progression of VILI, evidenced by improvements in inflammatory biomarkers, atelectasis, gas volumes in the parenchymal airspaces, and the stiffness of the pulmonary system.
• Hodges, M., Zgheib, C., & Liechty, K. (2021). A Large Mammalian Model of Myocardial Regeneration after Myocardial Infarction in Fetal Sheep. Adv Wound Care (New Rochelle), 10(4). doi:10.1089/wound.2018.0894
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  Objective: Ischemic heart disease accounts for over 20% of all deaths worldwide. As the global population faces a rising burden of chronic diseases, such as hypertension, hyperlipidemia, and diabetes, the prevalence of heart failure due to ischemic heart disease is estimated to increase. We sought to develop a model that may more accurately identify therapeutic targets to mitigate the development of heart failure following myocardial infarction (MI). Approach: Having utilized fetal large mammalian models of scarless wound healing, we proposed a fetal ovine model of myocardial regeneration after MI. Results: Use of this model has identified critical pathways in the mammalian response to MI, which are differentially activated in the regenerative, fetal mammalian response to MI when compared to the reparative, scar-forming, adult mammalian response to MI. Innovation: While the foundation of myocardial regeneration research has been built on zebrafish and rodent models, effective therapies derived from these disease models have been lacking; therefore, we sought to develop a more representative ovine model of myocardial regeneration after MI to improve the identification of therapeutic targets designed to mitigate the development of heart failure following MI. Conclusions: To develop therapies aimed at mitigating this rising burden of disease, it is critical that the animal models we utilize closely reflect the physiology and pathology we observe in human disease. We encourage use of this ovine large mammalian model to facilitate identification of therapies designed to mitigate the growing burden of heart failure.
• Dewberry, L., Trecartin, A., Galambos, C., Hilton, S., Dannull, K., Zaretsky, M., Behrendt, N., Galan, H., Marwan, A., & Liechty, K. (2020). A congenital cystic pulmonary airway malformation occurring together with both an extralobar pulmonary sequestration and an esophageal duplication cyst. Clin Case Rep., 8(1). doi:10.1002/ccr3.2455
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  A foregut duplication cyst occurring together with both a congenital cystic pulmonary airway malformation and extralobar pulmonary sequestration is an unusual combination. Prenatal ultrasound, MRI, and postnatal CT are helpful for operative planning. Surgical resection is the definitive management for all three anomalies.
• Bermudez, D., Canning, D., & Liechty, K. (2011). Age and pro-inflammatory cytokine production: Wound-healing implications for scar-formation and the timing of genital surgery in boys. J Pediatr Urol, 7(3). doi:10.1016/j.jpurol.2011.02.013
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  Purpose: Fewer complications occur when hypospadias is repaired early in childhood. We hypothesize that the production of pro-inflammatory cytokines by fibroblasts from neonatal foreskin is decreased compared with fibroblasts from older boys. We believe that these age-related differences may explain the greater risk of complications following repair in older boys. Materials and methods: With IRB approval, we collected 15 samples of foreskin from boys undergoing elective circumcision. They were divided into one of three groups: a neonatal group (under 28 days), an intermediate age group (6 months-1 year), and an older age group (7-17-years-olds). Fibroblasts were cultured then incubated for 16 h with serum-free medium containing 0, 0.1, 1 or 10 ng/mL of PDGF. Supernatants were analyzed for production of IL-6 and IL-8 with quantitative ELISA. Fibroblasts had RT-PCR performed for IL-6, IL-8, IL-10, TGF-β1, TGF-β3 and TNF-α. Results: Fibroblasts from neonatal foreskin produced significantly less IL-6 and IL-8 at baseline and following stimulation with PDGF compared to the intermediate and older age groups (P < 0.01). Real-time PCR revealed greater expression of IL-6, IL-8, TNF-α and TGF-β1 mRNA in the older age groups (P < 0.05). Conclusions: There is a clear association between age and production of pro-inflammatory cytokines by genitourinary fibroblasts. This relationship exists at baseline and following stimulation with PDGF. The dramatic difference in levels of pro-inflammatory factors may explain the observed age-associated differences in wound scarring and stricture formation following hypospadias repair. Further clinical studies are needed, however, to validate this finding. © 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
• Liechty, K., Nesbit, M., Herlyn, M., Radu, A., Scott Adzick, N., & Crombleholme, T. (1999). Adenoviral-mediated overexpression of platelet-derived growth factor-b corrects ischemic impaired wound healing. Journal of Investigative Dermatology, 113(3). doi:10.1046/j.1523-1747.1999.00705.x
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  Chronic wounds represent a major clinical problem with significant morbidity and healthcare expenditures, but no effective therapies. Topical platelet-derived growth factor-BB trials have required large and repeated doses to achieve only a modest effect. We examined the ability of an adenovirus containing the platelet-derived growth factor-B transgene to improve the rate of wound healing through induction of platelet-derived growth factor-B overexpression in cells participating in the wound healing response. We treated excisional wounds in the ischemic rabbit ear, which have a 60% delay in healing, with vehicle, 106, or 108 plaque-forming units of an adenovirus containing the platelet-derived growth factor-B per wound (n = 19). At 7 d this resulted in a decrease in the epithelial gap from 3.4 ± 1 mm (mean ± SD) in vehicle-treated wounds to 1.9 ± 1.8 mm (mean ± SD, p < 0.05) when treated with 106 plaque-forming units of an adenovirus containing the platelet-derived growth factor-B, and 0.7 ± 1.1 mm (mean ± SD, p < 0.001) when treated with 108 plaque-forming units of an adenovirus containing the platelet-derived growth factor-B. Ischemic excisional wounds treated with 108 plaque-forming units of an adenovirus containing the platelet-derived growth factor-B even healed more rapidly than non-ischemic excisional wounds treated with vehicle (p < 0.05). In contrast, 5 μg of platelet-derived growth factor-BB protein (n = 2) resulted in only modest granulation tissue at the margin, but no significant differences in epithelial gap (3 ± 0.6 mm, mean ± SD). Plaque-forming units (106 or 108) of an adenovirus containing the β-galactosidase transgene (n = 4) impaired wound re-epithelialization with an epithelial gap of 5.11 ± 0.69 mm, mean ± SD, p < 0.004, and 3.8 ± 0.57 mm, mean ± SD, p < 0.07, respectively. Adenoviral-mediated gene transfer of platelet-derived growth factor-B overcame the ischemic defect in wound healing and offers promise in the treatment of chronic nonhealing wounds. The vulnerary effects of platelet- derived growth factor-B overexpression were sufficient to overcome the adverse effects of the adenovirus or transgene on wound healing.
• Christensen, R., Liechty, K., Koenig, J., Schibler, K., & Ohls, R. (1991). Administration of erythropoietin to newborn rats results in diminished neutrophil production. Blood, 78(5).
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  Very high concentrations of erythropoietin (epo), in clonogenic cultures, result in reduced production of neutrophils, and fetal progenitors are more sensitive to this effect of epo than are those of adults. However, the significance of this observation is unclear because no evidence of reduced neutrophil production has been presented following administration of recombinant epo to human or animal subjects. In the present study we injected newborn rats, beginning on the first day of life, with 20, 200, or 2,000 U epo/kg body weight, and measured serum epo concentrations after 2, 8, 24, or 48 hours. After selecting a dose that resulted in serum concentrations greater than 1,000 mU/mL (a concentration that resulted in down-modulation of neutrophil production from neonatal rat progenitors in vitro) other newborn rats were treated for 3 days with that dose (1,000 U epo/kg) or a vehicle control. Administration of epo resulted in increased hematocrits (P

Presentations

• Liechty, K. W. (2024, August). Fetal Surgery in Arizona 2024: State of the Art. Arizona Perinatal Trust Conference. Flagstaff, AZ.
• Liechty, K. W. (2024, June). Regeneration in Response to Injury: Lessons Learned from the Fetus. The University of Arizona College of Medicine Adventures in Curiosity and Care - SIMI 2024.
• Liechty, K. W. (2024, June). Wilms’ Tumor – Pediatric, Abdominal Pain - Acute – Pediatric, Abdominal Mass – Pediatric, Malrotation – Pediatric, Hypertrophic Pyloric Stenosis – Pediatric. The University of Arizona Department of Surgery Residency Chief Boot Camp. Tucson, Az.
• Liechty, K. W. (2024, October). Development of a Pediatric Fetal Neurosurgery Program. Arizona Neurosurgical Society Annual Meeting. Phoenix, AZ.
• Liechty, K. W. (2023, May). Regeneration in Response to Injury: Lessons Learned from the Fetus. University of Arizona Department of Surgery Research Day. Tucson, AZ: University of Arizona.
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  Lecture
• Liechty, K. W. (2023, November). Regeneration in Response to Injury: Lessons Learned from the Fetus. CarePoint Health Organization.
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  Lecture
• Liechty, K. W. (2023, November). Regeneration in Response to Injury: Lessons Learned from the Fetus. Skin Research Group of Canada 10th Annual Conference. Canada.
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  Lecture
• Liechty, K. W. (2023, November). Regeneration in Response to Injury: Lessons Learned from the Fetus. Surgery Grand Rounds. Tucson, AZ: University of Arizona.
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  Lecture
• Liechty, K. W. (2023, October). Regeneration in Response to Injury: Lessons Learned from the Fetus. Diabetic Wounds Treatment Consensus Panel. Connecticut: Yale University.
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  Lecture
• Liechty, K. W. (2023, October). Regeneration in Response to Injury: Lessons Learned from the Fetus. Robert Christensen Lectureship. Utah: University of Utah.
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  Lecture

Others

• Guthrie, E., Fortier, K., Liechty, K. W., & Price, N. (2023, August). Pediatric Surgical Antibiotic Preoperative Prophylaxis Guidelines for Elective Surgery.
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  Guideline to assist in choosing antibiotic prophylaxis for children undergoing elective procedures.  Used by the Banner system.