Publications by authors named "Sean Noona"

4 Publications

  • Page 1 of 1

Endothelial Transient Receptor Potential V4 Channels Mediate Lung Ischemia-Reperfusion Injury.

Ann Thorac Surg 2021 May 4. Epub 2021 May 4.

Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA. Electronic address:

Background: Lung ischemia-reperfusion injury (IRI), involving severe inflammation and edema, is a major cause of primary graft dysfunction following transplant. Activation of transient receptor potential vanilloid 4 (TRPV4) channels modulates vascular permeability. Thus, this study tests the hypothesis that endothelial TRPV4 channels mediate lung IRI.

Methods: C57BL/6 wild-type (WT), TRPV4, tamoxifen-inducible endothelial TRPV4 knockout (TRPV4), and tamoxifen-treated control (TRPV4) mice underwent lung IR using a left lung hilar-ligation model (n≥6 mice/group). WT mice were also treated with a TRPV4-specific inhibitor (GSK2193874; 1mg/kg) (WT+GSK219). Partial pressure of oxygen (PaO), edema (wet-to-dry weight ratio), compliance, neutrophil infiltration, and cytokine concentrations in bronchioalveolar lavage fluid were assessed. Pulmonary microvascular endothelial cells (PMVECs) were characterized in vitro following exposure to hypoxia-reoxygenation.

Results: Compared to WT, PaO following IR was significantly improved in TRPV4 mice (133.1±43.9 vs 427.8±83.1 mmHg, p<0.001) and WT+GSK219 mice (133.1±43.9 vs 447.0±67.6 mmHg, p<0.001). Pulmonary edema and neutrophil infiltration were also significantly reduced after IR in TRPV4 and WT+GSK219 mice versus WT. TRPV4 mice following IR demonstrated significantly improved oxygenation versus control (109.2±21.6 vs 405.3±41.4 mmHg, p<0.001) as well as significantly improved compliance, and significantly less edema, neutrophil infiltration and proinflammatory cytokine production (TNF-α, CXCL1, IL-17, IFN-γ). Hypoxia-reoxygenation-induced permeability and CXCL1 expression by PMVECs was significantly attenuated by TRPV4 inhibitors.

Conclusions: Endothelial TRPV4 plays a key role in vascular permeability and lung inflammation following IR. TRPV4 channels may be a promising therapeutic target to mitigate lung IRI and decrease the incidence of primary graft dysfunction following transplant. (Word Count: 249/250).
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http://dx.doi.org/10.1016/j.athoracsur.2021.04.052DOI Listing
May 2021

Quadriceps Strength Is Influenced by Skeletal Maturity in Adolescents Recovering From Anterior Cruciate Ligament Reconstruction.

J Pediatr Orthop 2021 Feb;41(2):e141-e146

Departments of Orthopaedic Surgery.

Background: Anterior cruciate ligament injuries and anterior cruciate ligament reconstructions (ACLRs) are common, especially in adolescent patients. Recovery of strength, jumping performance, and perceived/subjective function are often used to make a return to sports decisions after injury. It is unknown how skeletal maturity may influence strength recovery after ACLR. The purpose of this study was to compare the strength and patient-reported outcomes in adolescent ACLR patients with and without open distal femur and proximal tibia physes.

Methods: One hundred seventeen consecutive patients under the age of 18 were referred for routine strength and subjective outcomes evaluation following ACLR, 100 were included in the final analyses after excluding those with prior injuries, those tested outside for 4 to 12 month postoperative window, and those with incomplete clinical data. All study patients completed patient-reported outcomes, and underwent isometric and isokinetic testing of knee extensor and flexor strength to calculate normalized peak torque and limb symmetry. Statistical analyses were performed on all outcomes data using a 2×2 (physeal status: open, closed; and sex: male, female) with analysis of covariance where age and preoperative activity level were used as covariates.

Results: A significant interaction between sex and physeal status for isokinetic knee extension peak torque and isometric knee extension peak torque, and limb symmetry index was found. This indicated that males with open physes were stronger and more symmetric than males with closed physes and females with open physes at ~6 months post-ACLR. There were no differences between sexes for patients with closed physes. No interactions were observed for flexion strength. Male patients and patients with open physes had higher perceived knee function compared with their corresponding counterparts.

Conclusions: After ACLR, adolescent patients with open physes had higher quadriceps strength compared with patients with closed physes. Overall, those skeletally less mature patients actually fared better on the functional strength tests, suggesting that functional recovery is not hindered by the presence of an incompletely closed physis.

Level Of Evidence: Level III-retrospective comparative study.
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http://dx.doi.org/10.1097/BPO.0000000000001706DOI Listing
February 2021

Benefits and barriers to pediatric tele-urology during the COVID-19 pandemic.

J Pediatr Urol 2020 Dec 8;16(6):840.e1-840.e6. Epub 2020 Oct 8.

Department of Urology, University of Virginia, Charlottesville, VA, USA. Electronic address:

Introduction: Telemedicine video visits are an under-utilized form of delivering health care. However due to the COVID-19 pandemic, practices are rapidly adapting telemedicine for patient care. We describe our experience in rapidly introducing video visits in a tertiary academic pediatric urology practice, serving primarily rural patients during the COVID-19 pandemic.

Objective: The primary aim of this study was to assess visit success rate and identify barriers to completing video visits. The secondary aim identified types of pathologies feasible for video visits and travel time saved. We hypothesize socioeconomic status is a predictor of a successful visit.

Materials And Methods: Data was prospectively collected and analyzed on video visits focusing on visit success, defined by satisfactory completion of the visit as assessed by the provider. Other variables collected included duration, video platform and technical problems. Retrospective data was collected via chart review and analyzed including demographics, insurance, and distance to care. Socioeconomic status was estimated using the Distressed Communities Index generated for patient zip code.

Results/discussion: Out of 116 attempted visits, 81% were successful. The top two reasons for failure were "no-show" (64%) and inability to connect (14%). Success versus failure of visit was similar for patient age (p = 0.23), sex (p = 0.42), type of visit (initial vs. established) (p = 0.51), and socioeconomic status (p = 0.39). After adjusting for race, socioeconomic status, and type of provider, having public insurance remained a significant predictor of failure (p = 0.017). Successful visits were conducted on multiple common pediatric urologic problems (excluding visits requiring palpation on exam), and video was sufficient for physical exams in most cases (Summary Table). A median of 2.25 h of travel time was saved.

Conclusions: While socioeconomic status, estimated using the Distressed Communities Index, did not predict success of video visits, patients with public insurance were more likely to have a failed video visit. There is compelling evidence that effective video visits for certain pathologies can be rapidly achieved in a pediatric urology practice with minimal preparation time.
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http://dx.doi.org/10.1016/j.jpurol.2020.09.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543732PMC
December 2020

Does renal mass biopsy influence multidisciplinary treatment recommendations?

Scand J Urol 2020 Feb 23;54(1):27-32. Epub 2019 Dec 23.

Department of Urology, University of Virginia, Charlottesville, VA, USA.

To examine how a multidisciplinary team approach incorporating renal mass biopsy (RMB) into decision making changes the management strategy. A multidisciplinary team comprised of a radiology proceduralist, a pathologist and urologists convened monthly for renal mass conference with a structured presentation of patient demographics, co-mborbidities, tumor pathology, laboratory and radiographic features. Biopsy protocol was standardized to an 18-gauge core needle biopsy using a sheathed apparatus under renal ultrasound guidance. Biopsy diagnostic rate, and concordance with nephrectomy specimens were summarized. Descriptive statistics were used to evaluate influence of RMB on management decisions. A total of 83 patients with a ≤4 cm mass were discussed, and 66% of patients underwent RMB. Of those, 87% were diagnostic with 9% of core biopsies showing benign pathology. Active surveillance (AS) was recommended for 34% of patients with biopsy data as compared to 64% of those without biopsy. Ablation was recommended for 38% of the biopsy cohort compared to 7% without biopsy. Partial nephrectomy rates were similar for both cohorts, approximately 17% and 22%, respectively. Our complication rate was 1.5%, with only 1 Clavien-Dindo Grade 2 complication. Histology was concordant in 93% of patients that ultimately underwent partial nephrectomy after biopsy. Over half of our SRM patients underwent a RMB that provided a diagnosis in 85% of cases. RMB aided in shared decision making by providing insight into the biology of renal masses, which helps to guide multidisciplinary management and consideration of nephron sparing options.
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http://dx.doi.org/10.1080/21681805.2019.1703805DOI Listing
February 2020