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Article ; Online: The effect of single ventricle congenital heart disease on recurrence risk of pneumatosis intestinalis in neonates.

Louiselle, Amanda E / Niemiec, Stephen M / Derderian, S Christopher / SooHoo, Megan M / Acker, Shannon N

2022 Volume 38, Issue 10, Page(s) 1399–1404

Abstract: Purpose: Congenital heart disease (CHD) is a risk factor for the development of pneumatosis intestinalis (PI). Patients with single ventricle physiology (SVP) may be at higher risk of developing PI secondary to variations in systemic blood flow which ... ...

Abstract	Purpose: Congenital heart disease (CHD) is a risk factor for the development of pneumatosis intestinalis (PI). Patients with single ventricle physiology (SVP) may be at higher risk of developing PI secondary to variations in systemic blood flow which affect bowel perfusion when compared to patients with biventricular physiology (BVP). We hypothesized that patients with SVP would have increased risk of recurrent PI. Methods: A retrospective review was done from 10/2014 through 05/2020 with patients that met the following criteria: CHD, radiographic evidence of PI, and less than 1 year of age. Groups were divided based on ventricular physiology. Primary outcome was radiographic recurrence of PI and secondary outcomes were average antibiotic duration, NPO duration, median length of stay, need for GI operation, and death from PI. Results: A total of 51 patients were included, 34 with SVP and 17 with BVP. 26.47% of SVP had recurrence of PI whereas no BVP experienced a recurrence of PI. There was no significant difference in any of the secondary outcomes. Conclusion: Our data suggest that patients with SVP are more likely to have recurrence of radiographic PI. We may need to consider patients with SVP that get PI as their own separate group.
MeSH term(s)	Heart Defects, Congenital/complications ; Heart Defects, Congenital/diagnostic imaging ; Humans ; Infant, Newborn ; Intestines/surgery ; Pneumatosis Cystoides Intestinalis/complications ; Pneumatosis Cystoides Intestinalis/diagnostic imaging ; Retrospective Studies ; Risk Factors
Language	English
Publishing date	2022-07-19
Publishing country	Germany
Document type	Journal Article
ZDB-ID	632773-4
ISSN	1437-9813 ; 0179-0358
ISSN (online)	1437-9813
ISSN	0179-0358
DOI	10.1007/s00383-022-05171-6
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Zs.A 2138: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Macrophage polarization and diabetic wound healing.

Louiselle, Amanda E / Niemiec, Stephen M / Zgheib, Carlos / Liechty, Kenneth W

Translational research : the journal of laboratory and clinical medicine

2021 Volume 236, Page(s) 109–116

Abstract: Diabetes mellitus is a costly disease and nearly one-third of these costs are attributed to management of diabetic foot disease including chronic, non-healing, diabetic foot ulcers. Therefore, much effort has been placed into understanding the ... ...

Abstract	Diabetes mellitus is a costly disease and nearly one-third of these costs are attributed to management of diabetic foot disease including chronic, non-healing, diabetic foot ulcers. Therefore, much effort has been placed into understanding the pathogenesis of diabetic wounds and novel therapeutics. A relatively new area of interest has been macrophage polarization and its role in diabetic wound healing. Diabetic wounds show dysregulated and persistent M1 (pro-inflammatory) macrophage polarization whereas normal wounds will display a transition to M2 (pro-healing) macrophages around day three after wounding. We reviewed factors known to affect macrophage polarization, mostly focused on those that contribute to M2 macrophage polarization, and potential treatments that at least in part target macrophage polarization in the diabetic wound bed. Much of the work has been aimed at reducing hyperglycemia and encouraging pro-inflammatory cytokine neutralization or decreased expression given this has a significant role in producing M1 macrophages. Treatment of diabetic wounds will likely require a multi-modal approach including management of underlying diabetes and control of hyperglycemia, topical therapeutics, and prevention of secondary infection and inflammation.
MeSH term(s)	Animals ; Cell Polarity ; Diabetes Mellitus/genetics ; Diabetes Mellitus/pathology ; Diabetes Mellitus/therapy ; Humans ; Macrophages/pathology ; Phenotype ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; Wound Healing/genetics
Chemical Substances	RNA, Long Noncoding
Language	English
Publishing date	2021-06-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2246684-8
ISSN	1878-1810 ; 1532-6543 ; 1931-5244
ISSN (online)	1878-1810 ; 1532-6543
ISSN	1931-5244
DOI	10.1016/j.trsl.2021.05.006
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Article ; Online: Role of microRNAs in Pressure Ulcer Immune Response, Pathogenesis, and Treatment.

Niemiec, Stephen M / Louiselle, Amanda E / Liechty, Kenneth W / Zgheib, Carlos

International journal of molecular sciences

2020 Volume 22, Issue 1

Abstract: Pressure ulcers are preventable, yet highly prevalent, chronic wounds that have significant patient morbidity and high healthcare costs. Like other chronic wounds, they are characterized by impaired wound healing due to dysregulated immune processes. ... ...

Abstract	Pressure ulcers are preventable, yet highly prevalent, chronic wounds that have significant patient morbidity and high healthcare costs. Like other chronic wounds, they are characterized by impaired wound healing due to dysregulated immune processes. This review will highlight key biochemical pathways in the pathogenesis of pressure injury and how this signaling leads to impaired wound healing. This review is the first to comprehensively describe the current literature on microRNA (miRNA, miR) regulation of pressure ulcer pathophysiology.
MeSH term(s)	Animals ; Apoptosis ; Disease Management ; Disease Susceptibility ; Extracellular Matrix ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; Immunity/genetics ; MicroRNAs/genetics ; Oxidative Stress ; Pressure Ulcer/etiology ; Pressure Ulcer/metabolism ; Pressure Ulcer/pathology ; Pressure Ulcer/therapy ; RNA Interference ; Reperfusion Injury/complications ; Reperfusion Injury/etiology ; Reperfusion Injury/metabolism ; Signal Transduction ; Wound Healing/genetics
Chemical Substances	MicroRNAs
Language	English
Publishing date	2020-12-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22010064
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Article ; Online: Third-trimester percentage predicted lung volume and percentage liver herniation as prognostic indicators in congenital diaphragmatic hernia.

Niemiec, Stephen M / Louiselle, Amanda E / Phillips, Ryan / Gien, Jason / Zaretsky, Michael V / Derderian, Sarkis C / Liechty, Kenneth W / Meyers, Mariana L

Pediatric radiology

2022 Volume 53, Issue 3, Page(s) 479–486

Abstract: Background: Over the last two decades, fetal imaging has greatly improved, and new prenatal imaging measurements have been developed to characterize congenital diaphragmatic hernia (CDH) severity.: Objective: To determine the best prenatal imaging ... ...

Abstract	Background: Over the last two decades, fetal imaging has greatly improved, and new prenatal imaging measurements have been developed to characterize congenital diaphragmatic hernia (CDH) severity. Objective: To determine the best prenatal imaging predictor of postnatal CDH outcomes, including use of extracorporeal membrane oxygenation (ECMO) and in-hospital mortality, with particular attention to the percentage of liver herniation (%LH) as a predictor. Additionally, we sought to guide best practices across hospital systems including improved models of prenatal risk assessment. Materials and methods: We conducted a retrospective review of infants with left CDH who were prenatally diagnosed. We analyzed prenatal imaging measurements including observed-to-expected (O/E) lung-to-head ratio (LHR) on US, percentage predicted lung volume (PPLV) on MRI, and O/E total fetal lung volume (TFLV) and %LH on MRI. We compared prenatal imaging characteristics for infants with (1) in-hospital postnatal mortality and (2) use of ECMO. Then we performed multivariate logistic regression to determine independent predictors of postnatal outcomes. Results: We included 63 infants with a median gestation of 34 weeks at the time of prenatal MRI. Low O/E LHR (31.2 vs. 50, P < 0.0001), PPLV (14.7 vs. 22.6, P < 0.0001) and O/E TLFV (24.6 vs. 38.3, P < 0.0001) and high %LH (15.1 vs. 2.1, P = 0.0006) were associated with worse postnatal outcomes; however, only PPLV was predictive of survival and need for ECMO on multivariable analysis. PPLV survival to discharge model showed an area under the curve (AUC) of 0.93 (95% confidence interval [CI]: 0.86, 0.99), P < 0.0001; and an odds ratio of 68.7 (95% CI: 6.5-2,302), P = 0.003. PPLV need for ECMO model showed AUC = 0.87 (95% CI: 0.78, 0.96), P < 0.0001; and odds ratio = 20.1 (95% CI: 3.1-226.3), P = 0.011. Conclusion: Low O/E LHR, PPLV and O/E TFLV and high %LH in the third trimester are associated with worse postnatal outcomes. PPLV most strongly predicted outcome using a logistic regression model. Percentage of liver herniation was not an independent predictor of outcomes.
MeSH term(s)	Pregnancy ; Female ; Humans ; Hernias, Diaphragmatic, Congenital ; Pregnancy Trimester, Third ; Prognosis ; Lung/diagnostic imaging ; Lung Volume Measurements/methods ; Liver ; Magnetic Resonance Imaging ; Retrospective Studies ; Ultrasonography, Prenatal
Language	English
Publishing date	2022-10-27
Publishing country	Germany
Document type	Journal Article
ZDB-ID	124459-0
ISSN	1432-1998 ; 0301-0449
ISSN (online)	1432-1998
ISSN	0301-0449
DOI	10.1007/s00247-022-05538-w
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Zs.A 927: Show issues

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Article ; Online: Muscle Flap Technique Safe for On-ECMO Congenital Diaphragmatic Hernia Repair.

Vaughn, Alyssa E / Lyttle, Bailey D / Louiselle, Amanda E / Cooper, Emily / Niemiec, Stephen M / Phillips, Ryan / Hilton, Sarah A / Kinsella, John P / Gien, Jason / Derderian, S Christopher / Liechty, Kenneth W

Journal of pediatric surgery

2023 Volume 59, Issue 5, Page(s) 962–968

Abstract: Introduction: 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 ... ...

Abstract	Introduction: 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. Methods: A single-center retrospective comparative study of patients who underwent on-ECMO CDH repair between 2008 and 2022 was performed. Results: Fifty-two patients met inclusion criteria: 18 patch (34.6%) and 34 flap (65.4%). There was no difference in CDH severity between groups. On univariate analysis, reoperation for surgical bleeding was lower following flap repair compared to patch (23.5% vs 55.6%, respectively; p = 0.045), 48-h postoperative blood product transfusion was lower after flap repair (132 mL/kg vs 273.5 mL/kg patch; p = 0.006), and two-year survival was increased in the flap repair group compared to patch (53.1% vs 17.7%, respectively; p = 0.036). On multivariate analysis adjusting for CDH side, day on ECMO repaired, and day of life CDH repaired, flap repair was significantly associated with lower five-day postoperative packed red blood cell transfusion amount, improved survival to hospital discharge, and improved two-year survival. Conclusions: Our experience suggests that the muscle flap technique for on-ECMO CDH repair is associated with reduced bleeding complications compared to prosthetic patch repair, which may in part be responsible for the improved survival seen in the flap repair group. These results support the flap repair technique as a favored method for on-ECMO CDH repair. Level of evidence: Level III.
MeSH term(s)	Humans ; Hernias, Diaphragmatic, Congenital/surgery ; Retrospective Studies ; Extracorporeal Membrane Oxygenation ; Diaphragm ; Surgical Flaps
Language	English
Publishing date	2023-12-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	80165-3
ISSN	1531-5037 ; 0022-3468
ISSN (online)	1531-5037
ISSN	0022-3468
DOI	10.1016/j.jpedsurg.2023.11.022
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Zs.A 607: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Photopolymerized Zwitterionic Hydrogels with a Sustained Delivery of Cerium Oxide Nanoparticle-miR146a Conjugate Accelerate Diabetic Wound Healing.

Stager, Michael A / Bardill, James / Raichart, Alexandra / Osmond, Matthew / Niemiec, Stephen / Zgheib, Carlos / Seal, Sudipta / Liechty, Kenneth W / Krebs, Melissa D

ACS applied bio materials

2022 Volume 5, Issue 3, Page(s) 1092–1103

Abstract: In the United States, $87 billion per year is spent on the care of diabetic ulcers alone. Although the pathophysiology of diabetic wound healing is multifaceted, high systemic levels of inflammation and increased reactive oxygen species are often ... ...

Abstract	In the United States, $87 billion per year is spent on the care of diabetic ulcers alone. Although the pathophysiology of diabetic wound healing is multifaceted, high systemic levels of inflammation and increased reactive oxygen species are often implicated in the wound healing impairment. Zwitterionic materials have been demonstrated to reduce inflammation and increase extracellular matrix deposition in wound beds, and here, we demonstrate a fabrication method for photopolymerized zwitterionic hydrogels that also enables sustained drug delivery over time. A therapeutic molecule of interest that is examined in this work is cerium oxide nanoparticle tagged with microRNA-146a (CNP-miR146a) to combat both oxidative stress and inflammation. The hydrogels are composed of zwitterionic and nonzwitterionic monomers, and the hydrogel formation occurs in the absence of a crosslinker. The hydrogels exhibit a wide range of stiffness and mechanical properties depending on their monomer content. Additionally, these hydrogels exhibit sustained release of nanoparticles and proteins. Finally, when employed in an
MeSH term(s)	Animals ; Cerium ; Diabetes Mellitus ; Hydrogels ; Inflammation ; Mice ; Nanoparticles ; Wound Healing
Chemical Substances	Hydrogels ; Cerium (30K4522N6T) ; ceric oxide (619G5K328Y)
Language	English
Publishing date	2022-02-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2576-6422
ISSN (online)	2576-6422
DOI	10.1021/acsabm.1c01155
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Article ; Online: Early outcomes of a myofascial repair technique for fetal myelomeningocele.

Vaughn, Alyssa E / Louiselle, Amanda E / Tong, Suhong / Niemiec, Stephen M / Ahmad, Saliha / Zaretsky, Michael / Galan, Henry L / Behrendt, Nicholas / Wilkinson, C Corbett / O'Neill, Brent / Handler, Michael / Derderian, S Christopher / Mirsky, David M / Liechty, Kenneth W

Journal of pediatric surgery

2022

Abstract: Purpose: 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 ... ...

Abstract	Purpose: 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. Methods: A single-center retrospective study of patients who underwent fetal MMC or myeloschisis repair between March 2013 and February 2022 was performed. Outcomes were evaluated (n = 70 prior to July 2019, n = 34 after July 2019). Statistical significance was determined by Fisher's exact and Chi square tests (p < 0.05 significant). Results: Patients who underwent myofascial closure were less likely to require a patch for skin closure (14.7% vs 58.6%, p < 0.0001). Myofascial closure was also associated with an increased rate of HBH improvement on two-week postoperative fetal MRI (93.9% vs 65.7%, p = 0.002). Surgically-treated HCP at one year was lower in the myofascial closure group (n = 21), however this did not reach statistical significance (23.8% vs 41.9%, p = 0.19). Conclusions: We conclude that the myofascial closure technique for repair of fetal MMC and myeloschisis is associated with significantly decreased need for patch closure and improvement in hindbrain herniation compared to our previous skin closure technique. These results support a surgical approach that employs a multilayer watertight closure.
Language	English
Publishing date	2022-09-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	80165-3
ISSN	1531-5037 ; 0022-3468
ISSN (online)	1531-5037
ISSN	0022-3468
DOI	10.1016/j.jpedsurg.2022.09.030
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Zs.A 607: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Cerium oxide nanoparticle conjugation to microRNA-146a mechanism of correction for impaired diabetic wound healing.

Dewberry, Lindel C / Niemiec, Stephen M / Hilton, Sarah A / Louiselle, Amanda E / Singh, Sushant / Sakthivel, Tamil S / Hu, Junyi / Seal, Sudipta / Liechty, Kenneth W / Zgheib, Carlos

Nanomedicine : nanotechnology, biology, and medicine

2021 Volume 40, Page(s) 102483

Abstract: Diabetic wounds represent a significant healthcare burden and are characterized by impaired wound healing due to increased oxidative stress and persistent inflammation. We have shown that CNP-miR146a synthesized by the conjugation of cerium oxide ... ...

Abstract	Diabetic wounds represent a significant healthcare burden and are characterized by impaired wound healing due to increased oxidative stress and persistent inflammation. We have shown that CNP-miR146a synthesized by the conjugation of cerium oxide nanoparticles (CNP) to microRNA (miR)-146a improves diabetic wound healing. CNP are divalent metal oxides that act as free radical scavenger, while miR146a inhibits the pro-inflammatory NFκB pathway, so CNP-miR146a has a synergistic role in modulating both oxidative stress and inflammation. In this study, we define the mechanism(s) by which CNP-miR146a improves diabetic wound healing by examining immunohistochemical and gene expression analysis of markers of inflammation, oxidative stress, fibrosis, and angiogenesis. We have found that intradermal injection of CNP-miR146a increases wound collagen, enhances angiogenesis, and lowers inflammation and oxidative stress, ultimately promoting faster closure of diabetic wounds.
MeSH term(s)	Cerium/chemistry ; Cerium/pharmacology ; Diabetes Mellitus ; Humans ; MicroRNAs/metabolism ; Nanoparticles/chemistry ; Wound Healing
Chemical Substances	MicroRNAs ; Cerium (30K4522N6T) ; ceric oxide (619G5K328Y)
Language	English
Publishing date	2021-11-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2183417-9
ISSN	1549-9642 ; 1549-9634
ISSN (online)	1549-9642
ISSN	1549-9634
DOI	10.1016/j.nano.2021.102483
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Article ; Online: Lung function improves after delayed treatment with CNP-miR146a following acute lung injury.

Niemiec, Stephen M / Hilton, Sarah A / Wallbank, Alison / Louiselle, Amanda E / Elajaili, Hanan / Hu, Junyi / Singh, Sushant / Seal, Sudipta / Nozik, Eva / Smith, Bradford / Zgheib, Carlos / Liechty, Kenneth W

Nanomedicine : nanotechnology, biology, and medicine

2021 Volume 40, Page(s) 102498

Abstract: Acute respiratory distress syndrome (ARDS) is a highly morbid pulmonary disease characterized by hypoxic respiratory failure. Its pathogenesis is characterized by unrestrained oxidative stress and inflammation, with long-term sequelae of pulmonary ... ...

Abstract	Acute respiratory distress syndrome (ARDS) is a highly morbid pulmonary disease characterized by hypoxic respiratory failure. Its pathogenesis is characterized by unrestrained oxidative stress and inflammation, with long-term sequelae of pulmonary fibrosis and diminished lung function. Unfortunately, prior therapeutic ARDS trials have failed and therapy is limited to supportive measures. Free radical scavenging cerium oxide nanoparticles (CNP) conjugated to the anti-inflammatory microRNA-146a (miR146a), termed CNP-miR146a, have been shown to prevent acute lung injury in a pre-clinical model. In this study, we evaluated the potential of delayed treatment with CNP-miR146a at three or seven days after injury to rescue the lung from acute injury. We found that intratracheal CNP-miR146a administered three days after injury lowers pulmonary leukocyte infiltration, reduce inflammation and oxidative stress, lower pro-fibrotic gene expression and collagen deposition in the lung, and ultimately improve pulmonary function.
MeSH term(s)	Acute Lung Injury/drug therapy ; Acute Lung Injury/pathology ; Cerium ; Humans ; Lung/pathology ; Lung Injury/pathology ; Nanoparticles ; Time-to-Treatment
Chemical Substances	Cerium (30K4522N6T) ; ceric oxide (619G5K328Y)
Language	English
Publishing date	2021-11-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2183417-9
ISSN	1549-9642 ; 1549-9634
ISSN (online)	1549-9642
ISSN	1549-9634
DOI	10.1016/j.nano.2021.102498
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Article ; Online: Silk fibroin nanofibrous mats for visible sensing of oxidative stress in cutaneous wounds.

Singh, Sushant / Cortes, Gabriela / Kumar, Udit / Sakthivel, Tamil S / Niemiec, Stephen M / Louiselle, Amanda E / Azeltine-Bannerman, Mark / Zgheib, Carlos / Liechty, Kenneth W / Seal, Sudipta

Biomaterials science

2020 Volume 8, Issue 21, Page(s) 5900–5910

Abstract: Wound healing is of major clinical concern and is constantly being explored for early restoration and enhanced recovery. While the etiology of the wound healing is multifactorial, high inflammation and increased oxidative stress which results in chronic ... ...

Abstract	Wound healing is of major clinical concern and is constantly being explored for early restoration and enhanced recovery. While the etiology of the wound healing is multifactorial, high inflammation and increased oxidative stress which results in chronic inflammation, endothelial dysfunction and collagen degradation, delay the overall healing process. Thus, visual sensing of the oxidative stress would be highly informative in the successful implementation of wound healing therapies based on specific requirements. In this study, electrospinning was used to fabricate silk fibroin nanofibrous mats infused with Amplex red capable of detecting hydrogen peroxide, a reactive oxygen molecule. These mats produced a visible change in color with the limit of detection at 1 μM H
MeSH term(s)	Animals ; Diabetes Mellitus, Experimental ; Fibroins ; Hydrogen Peroxide ; Mice ; Nanofibers ; Oxidative Stress ; Silk
Chemical Substances	Silk ; Fibroins (9007-76-5) ; Hydrogen Peroxide (BBX060AN9V)
Language	English
Publishing date	2020-09-25
Publishing country	England
Document type	Journal Article
ZDB-ID	2693928-9
ISSN	2047-4849 ; 2047-4830
ISSN (online)	2047-4849
ISSN	2047-4830
DOI	10.1039/d0bm01325k
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