Effects of microRNAs on angiogenesis in diabetic wounds

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

Surgical Necrotizing Enterocolitis – Can We Predict the Need for Gastrostomy Tube Placement?

Introduction: 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. Methods: A single-center retrospective study of infants with surgical NEC requiring ostomy creation between 2007 and 2021 was performed. Results: Eighty patients met inclusion criteria. A GT was placed in 45/80 (56.3%), of which 3/45 (6.7%) were placed before, 20/45 (44.4%) concurrently with, and 22/45 (48.9%) after ostomy reversal. Between those who did and did not require GT placement, there were no significant differences in gestational age (27 versus 27 wk, P = 0.94) or birth weight (830 g versus 1055 g, P = 0.36). Hospital length of stay was longer in the GT group (128.2 versus 70.9 d, P < 0.0001). Time from ostomy reversal to hospital discharge was shorter when performed concurrently with GT (56 versus 77 d, P = 0.02). There were no differences in short-term or long-term GT related complications based on timing of GT placement. Conclusions: GT placement occurred in approximately 50% of patients with surgical NEC and GT may be accomplished safely at the time of ostomy reversal thus reducing the need for an additional procedure.12 month embargo; first published 27 November 2023This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Lung volume reduction surgery for ipsilateral emphysematous bullae after congenital diaphragmatic hernia repair

Congenital diaphragmatic hernia (CDH) is characterized by a diaphragmatic defect with herniation of abdominal organs into the thoracic cavity. Outcomes are largely dependent on the degree of pulmonary hypoplasia and pulmonary hypertension, with the most severe cases associated with approximately 50% mortality. Long term pulmonary complications are well known, however, development of lobar emphysema leading to hemodynamic instability is exceedingly rare. We report the case of a patient with severe left-sided CDH who underwent successful diaphragmatic hernia repair but subsequently developed emphysematous bullous disease of the left lung with hemodynamic compromise, requiring emergent lung volume reduction surgery

Muscle Flap Technique Safe for On-ECMO Congenital Diaphragmatic Hernia Repair

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.12 month embargo; first published 08 December 2023This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

CNP-miR146a Decreases Inflammation in Murine Acute Infectious Lung Injury

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; p p p = 0.03). CNP-miR146a treatment significantly decreased proinflammatory gene expression (IL-6, IL-8, TNFα, IL-1β; p p p = 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