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Article ; Online: Novel Left Ventricular Unloading Strategies in Patients on Peripheral Venoarterial Extracorporeal Membrane Oxygenation Support.

Inglis, Sara S / Rosenbaum, Andrew N / Rizzo, Skylar A / Anderson, Jason H / Yalamuri, Suraj / Spencer, Philip J / Villavicencio, Mauricio A / Behfar, Atta

ASAIO journal (American Society for Artificial Internal Organs : 1992)

2024 Volume 70, Issue 5, Page(s) 396–403

Abstract: The purpose of this study was to evaluate left ventricular (LV) unloading strategies in patients supported with peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO). A retrospective review was conducted of all consecutive patients ... ...

Abstract	The purpose of this study was to evaluate left ventricular (LV) unloading strategies in patients supported with peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO). A retrospective review was conducted of all consecutive patients requiring VA-ECMO support for any indication, who underwent novel LV unloading strategies with either direct left atrial venoarterial (LAVA) cannulation or pulmonary artery venoarterial (PAVA) venting, in comparison to Impella and intra-aortic balloon pump (IABP). The primary outcome was successful bridge to transplant, LV assist device, or myocardial recovery. Forty-six patients (63% male, mean age 52.8 ± 17.6 years) were included. Fourteen patients (30%) underwent novel unloading with either LAVA or PAVA, 11 patients (24%) underwent IABP placement, and 21 patients (46%) underwent Impella insertion. In the novel LV unloading cohort, 10 patients (71%) survived to hospital discharge. Four patients (29%) were weaned from ECMO and eight patients (57%) underwent cardiac transplantation. Although a trend favoring cannula-based unloading for the primary outcome was noted, the cohort was too small for statistical significance (79% LAVA/PAVA, 57% Impella, 45% IABP; p = 0.21). However, probability of survival was greater in the LAVA/PAVA cohort compared to Impella and IABP ( p < 0.05). Thus, we demonstrate the efficacy of LA and PA cannulation as an alternative LV unloading strategy for patients supported with peripheral VA-ECMO.
MeSH term(s)	Humans ; Extracorporeal Membrane Oxygenation/methods ; Male ; Middle Aged ; Female ; Retrospective Studies ; Heart-Assist Devices ; Adult ; Aged ; Intra-Aortic Balloon Pumping/methods ; Treatment Outcome ; Heart Failure/therapy ; Heart Failure/physiopathology ; Heart Failure/surgery
Language	English
Publishing date	2024-01-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	759982-1
ISSN	1538-943X ; 0162-1432 ; 1058-2916
ISSN (online)	1538-943X
ISSN	0162-1432 ; 1058-2916
DOI	10.1097/MAT.0000000000002136
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Article ; Online: Clinical Reasoning: New-Onset Diplopia and Headache in a Patient With Metastatic Breast Cancer.

Rizzo, Skylar A / Flanagan, Eoin P / Trejo-Lopez, Jorge A / Toledano, Michel / Chia, Nicholas H

Neurology

2023 Volume 100, Issue 19, Page(s) 927–931

MeSH term(s)	Humans ; Female ; Diplopia/diagnosis ; Diplopia/etiology ; Breast Neoplasms/complications ; Headache/diagnosis ; Headache/etiology ; Clinical Reasoning ; Patients
Language	English
Publishing date	2023-02-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000206856
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Article ; Online: Pulmonary Biodistribution of Platelet-Derived Regenerative Exosomes in a Porcine Model.

Rizzo, Skylar A / Bagwell, Monique S / Schiebel, Paige / Rolland, Tyler J / Mahlberg, Ryan C / Witt, Tyra A / Nagel, Mary E / Stalboerger, Paul G / Behfar, Atta

International journal of molecular sciences

2024 Volume 25, Issue 5

Abstract: The purpose of this study was to evaluate the biodistribution of a platelet-derived exosome product (PEP), previously shown to promote regeneration in the setting of wound healing, in a porcine model delivered through various approaches. Exosomes were ... ...

Abstract	The purpose of this study was to evaluate the biodistribution of a platelet-derived exosome product (PEP), previously shown to promote regeneration in the setting of wound healing, in a porcine model delivered through various approaches. Exosomes were labeled with DiR far-red lipophilic dye to track and quantify exosomes in tissue, following delivery via intravenous, pulmonary artery balloon catheter, or nebulization in sus scrofa domestic pigs. Following euthanasia, far-red dye was detected by Xenogen IVUS imaging, while exosomal protein CD63 was detected by Western blot and immunohistochemistry. Nebulization and intravenous delivery both resulted in global uptake of exosomes within the lung parenchyma. However, nebulization resulted in the greatest degree of exosome uptake. Pulmonary artery balloon catheter-guided delivery provided the further ability to localize pulmonary delivery. No off-target absorption was noted in the heart, spleen, or kidney. However, the liver demonstrated uptake primarily in nebulization-treated animals. Nebulization also resulted in uptake in the trachea, without significant absorption in the esophagus. Overall, this study demonstrated the feasibility of pulmonary delivery of exosomes using nebulization or intravenous infusion to accomplish global delivery or pulmonary artery balloon catheter-guided delivery for localized delivery.
MeSH term(s)	Animals ; Swine ; Exosomes/metabolism ; Tissue Distribution ; Wound Healing ; Biological Transport ; Lung
Language	English
Publishing date	2024-02-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25052642
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Article ; Online: Nebulized platelet-derived extracellular vesicles attenuate chronic cigarette smoke-induced murine emphysema.

Xuan, Weixia / Wang, Shaohua / Alarcon-Calderon, Amarilys / Bagwell, Monique Simone / Para, Rachel / Wang, Faping / Zhang, Chujie / Tian, Xue / Stalboerger, Paul / Peterson, Timothy / Sabbah, Michael S / Du, Zeji / Sarrafian, Tiffany / Mahlberg, Ryan / Hillestad, Matthew L / Rizzo, Skylar A / Paradise, Christopher R / Behfar, Atta / Vassallo, Robert

Translational research : the journal of laboratory and clinical medicine

2024 Volume 269, Page(s) 76–93

Abstract: Chronic obstructive pulmonary disease (COPD) is a prevalent lung disease usually resulting from cigarette smoking (CS). Cigarette smoking induces oxidative stress, which causes inflammation and alveolar epithelial cell apoptosis and represents a ... ...

Abstract	Chronic obstructive pulmonary disease (COPD) is a prevalent lung disease usually resulting from cigarette smoking (CS). Cigarette smoking induces oxidative stress, which causes inflammation and alveolar epithelial cell apoptosis and represents a compelling therapeutic target for COPD. Purified human platelet-derived exosome product (PEP) is endowed with antioxidant enzymes and immunomodulatory molecules that mediate tissue repair. In this study, a murine model of CS-induced emphysema was used to determine whether nebulized PEP can influence the development of CS-induced emphysema through the mitigation of oxidative stress and inflammation in the lung. Nebulization of PEP effectively delivered the PEP vesicles into the alveolar region, with evidence of their uptake by type I and type II alveolar epithelial cells and macrophages. Lung function testing and morphometric assessment showed a significant attenuation of CS-induced emphysema in mice treated with nebulized PEP thrice weekly for 4 weeks. Whole lung immuno-oncology RNA sequencing analysis revealed that PEP suppressed several CS-induced cell injuries and inflammatory pathways. Validation of inflammatory cytokines and apoptotic protein expression on the lung tissue revealed that mice treated with PEP had significantly lower levels of S100A8/A9 expressing macrophages, higher levels of CD4+/FOXP3+ Treg cells, and reduced NF-κB activation, inflammatory cytokine production, and apoptotic proteins expression. Further validation using in vitro cell culture showed that pretreatment of alveolar epithelial cells with PEP significantly attenuated CS extract-induced apoptotic cell death. These data show that nebulization of exosomes like PEP can effectively deliver exosome cargo into the lung, mitigate CS-induced emphysema in mice, and suppress oxidative lung injury, inflammation, and apoptotic alveolar epithelial cell death.
MeSH term(s)	Animals ; Extracellular Vesicles/metabolism ; Pulmonary Emphysema/pathology ; Pulmonary Emphysema/etiology ; Mice ; Mice, Inbred C57BL ; Cigarette Smoking/adverse effects ; Blood Platelets/metabolism ; Humans ; Nebulizers and Vaporizers ; Oxidative Stress/drug effects ; Male ; Apoptosis/drug effects
Language	English
Publishing date	2024-02-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
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.2024.02.001
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Article ; Online: Percutaneous Mechanical Circulatory Support as a Bridge to Transplantation in Ebstein Anomaly.

Rizzo, Skylar A / Yalamuri, Suraj M / Rosenbaum, Andrew N / Anavekar, Nandan S / Miranda, William R / Daly, Richard / Dearani, Joseph A / Villavicencio, Mauricio / Behfar, Atta

Mayo Clinic proceedings

2023 Volume 98, Issue 4, Page(s) 626–630

Abstract: Ebstein anomaly is a rare congenital heart defect occurring in 0.0005% of the population because of mispositioning and malformation of the tricuspid valve. Here, we present the first description and associated imaging of percutaneous mechanical ... ...

Abstract	Ebstein anomaly is a rare congenital heart defect occurring in 0.0005% of the population because of mispositioning and malformation of the tricuspid valve. Here, we present the first description and associated imaging of percutaneous mechanical circulatory support in the setting of cardiogenic shock secondary to Ebstein anomaly.
MeSH term(s)	Humans ; Ebstein Anomaly ; Tricuspid Valve ; Heart Defects, Congenital ; Tricuspid Valve Insufficiency/etiology ; Shock, Cardiogenic
Language	English
Publishing date	2023-04-03
Publishing country	England
Document type	Case Reports
ZDB-ID	124027-4
ISSN	1942-5546 ; 0025-6196
ISSN (online)	1942-5546
ISSN	0025-6196
DOI	10.1016/j.mayocp.2023.01.003
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Article ; Online: Platelet-derived exosomes induce cell proliferation and wound healing in human endometrial cells.

Miller, Colleen M / L Enninga, Elizabeth Ann / Rizzo, Skylar A / Phillipps, Jordan / Guerrero-Cazares, Hugo / Destephano, Christopher C / Peterson, Timothy E / Stalboerger, Paul G / Behfar, Atta / Khan, Zaraq

Regenerative medicine

2022 Volume 17, Issue 11, Page(s) 805–817

Abstract: Aim: ...

Abstract	Aim:
MeSH term(s)	Cell Proliferation ; Endometrium ; Exosomes ; Female ; Humans ; Stromal Cells/metabolism ; Wound Healing
Language	English
Publishing date	2022-10-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2274500-2
ISSN	1746-076X ; 1746-0751
ISSN (online)	1746-076X
ISSN	1746-0751
DOI	10.2217/rme-2022-0095
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Zs.A 6627: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Exosome biopotentiated hydrogel restores damaged skeletal muscle in a porcine model of stress urinary incontinence.

Rolland, Tyler J / Peterson, Timothy E / Singh, Raman Deep / Rizzo, Skylar A / Boroumand, Soulmaz / Shi, Ao / Witt, Tyra A / Nagel, Mary / Kisby, Cassandra K / Park, Sungjo / Rowe, Lois A / Paradise, Christopher R / Becher, Laura R E / Paradise, Brooke D / Stalboerger, Paul G / Trabuco, Emanuel C / Behfar, Atta

NPJ Regenerative medicine

2022 Volume 7, Issue 1, Page(s) 58

Abstract: Urinary incontinence afflicts up to 40% of adult women in the United States. Stress urinary incontinence (SUI) accounts for approximately one-third of these cases, precipitating ~200,000 surgical procedures annually. Continence is maintained through the ... ...

Abstract	Urinary incontinence afflicts up to 40% of adult women in the United States. Stress urinary incontinence (SUI) accounts for approximately one-third of these cases, precipitating ~200,000 surgical procedures annually. Continence is maintained through the interplay of sub-urethral support and urethral sphincter coaptation, particularly during activities that increase intra-abdominal pressure. Currently, surgical correction of SUI focuses on the re-establishment of sub-urethral support. However, mesh-based repairs are associated with foreign body reactions and poor localized tissue healing, which leads to mesh exposure, prompting the pursuit of technologies that restore external urethral sphincter function and limit surgical risk. The present work utilizes a human platelet-derived CD41a and CD9 expressing extracellular vesicle product (PEP) enriched for NF-κB and PD-L1 and derived to ensure the preservation of lipid bilayer for enhanced stability and compatibility with hydrogel-based sustained delivery approaches. In vitro, the application of PEP to skeletal muscle satellite cells in vitro drove proliferation and differentiation in an NF-κB-dependent fashion, with full inhibition of impact on exposure to resveratrol. PEP biopotentiation of collagen-1 and fibrin glue hydrogel achieved sustained exosome release at 37 °C, creating an ultrastructural "bead on a string" pattern on scanning electron microscopy. Initial testing in a rodent model of latissimus dorsi injury documented activation of skeletal muscle proliferation of healing. In a porcine model of stress urinary incontinence, delivery of PEP-biopotentiated collagen-1 induced functional restoration of the external urethral sphincter. The histological evaluation found that sustained PEP release was associated with new skeletal muscle formation and polarization of local macrophages towards the regenerative M2 phenotype. The results provided herein serve as the first description of PEP-based biopotentiation of hydrogels implemented to restore skeletal muscle function and may serve as a promising approach for the nonsurgical management of SUI.
Language	English
Publishing date	2022-09-29
Publishing country	United States
Document type	Journal Article
ISSN	2057-3995
ISSN (online)	2057-3995
DOI	10.1038/s41536-022-00240-9
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Article ; Online: Author Correction: Exosome biopotentiated hydrogel restores damaged skeletal muscle in a porcine model of stress urinary incontinence.

NPJ Regenerative medicine

2022 Volume 7, Issue 1, Page(s) 65

Language	English
Publishing date	2022-10-31
Publishing country	United States
Document type	Published Erratum
ISSN	2057-3995
ISSN (online)	2057-3995
DOI	10.1038/s41536-022-00260-5
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Article ; Online: AAV-Mediated TAZ Gene Replacement Restores Mitochondrial and Cardioskeletal Function in Barth Syndrome.

Suzuki-Hatano, Silveli / Saha, Madhurima / Rizzo, Skylar A / Witko, Rachael L / Gosiker, Bennett J / Ramanathan, Manashwi / Soustek, Meghan S / Jones, Michael D / Kang, Peter B / Byrne, Barry J / Cade, W Todd / Pacak, Christina A

Human gene therapy

2018 Volume 30, Issue 2, Page(s) 139–154

Abstract: Barth syndrome (BTHS) is a rare mitochondrial disease that affects heart and skeletal muscle and has no curative treatment. It is caused by recessive mutations in the X-linked gene TAZ, which encodes tafazzin. To develop a clinically relevant gene ... ...

Abstract	Barth syndrome (BTHS) is a rare mitochondrial disease that affects heart and skeletal muscle and has no curative treatment. It is caused by recessive mutations in the X-linked gene TAZ, which encodes tafazzin. To develop a clinically relevant gene therapy to restore tafazzin function and treat BTHS, three different adeno-associated virus serotype 9 vectors were tested and compared to identify the optimal promoter-cytomegalovirus (CMV), desmin (Des), or a native tafazzin promoter (Taz)-for TAZ expression following intravenous administration of 1 × 10
MeSH term(s)	Animals ; Barth Syndrome/genetics ; Barth Syndrome/metabolism ; Barth Syndrome/physiopathology ; Barth Syndrome/therapy ; Dependovirus ; Female ; Genetic Therapy ; Genetic Vectors ; Humans ; Male ; Mice ; Mice, Transgenic ; Mitochondria, Muscle/genetics ; Mitochondria, Muscle/metabolism ; Mitochondria, Muscle/pathology ; Muscle, Skeletal/metabolism ; Muscle, Skeletal/pathology ; Muscle, Skeletal/physiopathology ; Recovery of Function/genetics ; Transcription Factors/biosynthesis ; Transcription Factors/genetics ; Transduction, Genetic
Chemical Substances	Transcription Factors ; tafazzin protein, mouse (EC 2.3.-)
Language	English
Publishing date	2018-10-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1028152-6
ISSN	1557-7422 ; 1043-0342
ISSN (online)	1557-7422
ISSN	1043-0342
DOI	10.1089/hum.2018.020
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Zs.A 2988: Show issues

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Article ; Online: Selective serotonin reuptake inhibitors ameliorate MEGF10 myopathy.

Saha, Madhurima / Rizzo, Skylar A / Ramanathan, Manashwi / Hightower, Rylie M / Santostefano, Katherine E / Terada, Naohiro / Finkel, Richard S / Berg, Jonathan S / Chahin, Nizar / Pacak, Christina A / Wagner, Richard E / Alexander, Matthew S / Draper, Isabelle / Kang, Peter B

Human molecular genetics

2019 Volume 28, Issue 14, Page(s) 2365–2377

Abstract: MEGF10 myopathy is a rare inherited muscle disease that is named after the causative gene, MEGF10. The classic phenotype, early onset myopathy, areflexia, respiratory distress and dysphagia, is severe and immediately life-threatening. There are no ... ...

Abstract	MEGF10 myopathy is a rare inherited muscle disease that is named after the causative gene, MEGF10. The classic phenotype, early onset myopathy, areflexia, respiratory distress and dysphagia, is severe and immediately life-threatening. There are no disease-modifying therapies. We performed a small molecule screen and follow-up studies to seek a novel therapy. A primary in vitro drug screen assessed cellular proliferation patterns in Megf10-deficient myoblasts. Secondary evaluations were performed on primary screen hits using myoblasts derived from Megf10-/- mice, induced pluripotent stem cell-derived myoblasts from MEGF10 myopathy patients, mutant Drosophila that are deficient in the homologue of MEGF10 (Drpr) and megf10 mutant zebrafish. The screen yielded two promising candidates that are both selective serotonin reuptake inhibitors (SSRIs), sertraline and escitalopram. In depth follow-up analyses demonstrated that sertraline was highly effective in alleviating abnormalities across multiple models of the disease including mouse myoblast, human myoblast, Drosophila and zebrafish models. Sertraline also restored deficiencies of Notch1 in disease models. We conclude that SSRIs show promise as potential therapeutic compounds for MEGF10 myopathy, especially sertraline. The mechanism of action may involve the Notch pathway.
MeSH term(s)	Animals ; Cell Line ; Cell Movement ; Cell Proliferation ; Citalopram/pharmacology ; Citalopram/therapeutic use ; Drosophila/drug effects ; Drosophila/genetics ; Drug Evaluation, Preclinical ; Humans ; Membrane Proteins/genetics ; Mice ; Mice, Knockout ; Muscle, Skeletal/metabolism ; Muscular Diseases/drug therapy ; Muscular Diseases/genetics ; Mutation ; Myoblasts/drug effects ; Myoblasts/metabolism ; Receptor, Notch1/metabolism ; Serotonin Uptake Inhibitors/pharmacology ; Serotonin Uptake Inhibitors/therapeutic use ; Sertraline/pharmacology ; Sertraline/therapeutic use ; Signal Transduction ; Zebrafish/genetics ; Zebrafish/metabolism
Chemical Substances	Megf10 protein, mouse ; Membrane Proteins ; Receptor, Notch1 ; Serotonin Uptake Inhibitors ; Citalopram (0DHU5B8D6V) ; Sertraline (QUC7NX6WMB)
Language	English
Publishing date	2019-06-29
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddz064
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