We sought to describe characteristics and operative outcomes of children who underwent repair of truncus arteriosus and identify risk factors for the occurrence of major adverse cardiac events (MACE) ...in the immediate postoperative period in a contemporary multicenter cohort.
We conducted a retrospective review of children who underwent repair of truncus arteriosus between 2009 and 2016 at 15 centers within the United States. Patients with associated interrupted or obstructed aortic arch were excluded. MACE was defined as the need for postoperative extracorporeal membrane oxygenation, cardiopulmonary resuscitation, or operative mortality. Risk factors for MACE were identified using multivariable logistic regression analysis and reported as odds ratios (ORs) with 95% confidence intervals (CIs).
We reviewed 216 patients. MACE occurred in 44 patients (20%) and did not vary significantly over time. Twenty-two patients (10%) received postoperative extracorporeal membrane oxygenation, 26 (12%) received cardiopulmonary resuscitation, and 15 (7%) suffered operative mortality. With multivariable logistic regression analysis (which included adjustment for center effect), factors independently associated with MACE were failure to diagnose truncus arteriosus before discharge from the nursery (OR, 3.1; 95% CI, 1.3-7.4), cardiopulmonary bypass duration >150 minutes (OR, 3.5; 95% CI, 1.5-8.5), and right ventricle-to-pulmonary artery conduit diameter >50 mm/m2 (OR, 4.7; 95% CI, 2.0-11.1).
In a contemporary multicenter analysis, 20% of children who underwent repair of truncus arteriosus experienced MACE. Early diagnosis, shorter duration of cardiopulmonary bypass, and use of smaller diameter right ventricle-to-pulmonary artery conduits represent potentially modifiable factors that could decrease morbidity and mortality in this fragile patient population.
Previous studies suggest that birth before 39 weeks’ gestational age (GA) is associated with higher perioperative mortality and morbidity after congenital heart surgery. The optimal approach to ...timing of cardiac operation in premature infants remains unclear. We investigated the impact of GA at birth and corrected GA at surgery on postoperative outcomes using the Pediatric Cardiac Critical Care Consortium (PC4) database.
Infants undergoing selected index cardiac operations before the end of the neonatal period were included (n = 2298). GA at birth and corrected GA at the time of the index cardiac operation were used as categorical predictors and fitted as a cubic spline to assess nonlinear relationships. The primary outcome was hospital mortality. Multivariable logistic regression models assessed the association between predictors and outcomes while adjusting for confounders.
Late-preterm (34-36 weeks) birth was associated with increased odds of mortality compared with full-term (39-40 weeks) birth, while early-term (37-38 weeks) birth was not associated with increased mortality. Corrected GA at surgery of 34 to 37 weeks compared with 40 to 44 weeks was associated with increased mortality. When analyzing corrected GA at surgery as a continuous predictor of outcome, odds of survival improve as patients approach 39 weeks corrected GA.
Contrary to previous literature, we did not find an association between early-term birth and hospital mortality at PC4 hospitals. Our analysis of the relationship between corrected GA and mortality suggests that operating closer to full-term corrected GA may improve survival.
Literature describing morbidity and mortality after truncus arteriosus repair is predominated by single-center reports. We created and analyzed a multicenter dataset to identify risk factors for late ...mortality and right ventricle-to-pulmonary artery (RV-PA) conduit reintervention for this patient population.
We retrospectively collected data on children who underwent repair of truncus arteriosus without concomitant arch obstruction at 15 centers between 2009 and 2016. Cox regression survival analysis was conducted to determine risk factors for late mortality, defined as death occurring after hospital discharge and greater than 30 days after operation. Probability of any RV-PA conduit reintervention was analyzed over time using Fine-Gray modeling.
We reviewed 216 patients with median follow-up of 2.9 years (range, 0.1 to 8.8). Operative mortality occurred in 15 patients (7%). Of the 201 survivors there were 14 (7%) late deaths. DiGeorge syndrome (hazard ratio HR, 5.4; 95% confidence interval CI, 1.6 to 17.8) and need for postoperative tracheostomy (HR, 5.9; 95% CI, 1.8 to 19.4) were identified as independent risk factors for late mortality. At least one RV-PA conduit catheterization or surgical reintervention was performed in 109 patients (median time to reintervention, 23 months; range, 0.3 to 93). Risk factors for reintervention included use of pulmonary or aortic homografts versus Contegra (Medtronic, Inc, Minneapolis, MN) bovine jugular vein conduits (HR, 1.9; 95% CI, 1.2 to 3.1) and smaller conduit size (HR per mm/m2, 1.05; 95% CI, 1.03 to 1.08).
In a multicenter dataset DiGeorge syndrome and need for tracheostomy postoperatively were found to be independent risk factors for late mortality after repair of truncus arteriosus, whereas risk of conduit reintervention was independently influenced by both initial conduit type and size.
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Multipotent adipose-derived stem cells (ASCs) are increasingly used for regenerative purposes such as soft tissue reconstruction following mastectomy; however, the ability of tumors to commandeer ASC ...functions to advance tumor progression is not well understood. Through the integration of physical sciences and oncology approaches we investigated the capability of tumor-derived chemical and mechanical cues to enhance ASC-mediated contributions to tumor stroma formation. Our results indicate that soluble factors from breast cancer cells inhibit adipogenic differentiation while increasing proliferation, proangiogenic factor secretion, and myofibroblastic differentiation of ASCs. This altered ASC phenotype led to varied extracellular matrix (ECM) deposition and contraction thereby enhancing tissue stiffness, a characteristic feature of breast tumors. Increased stiffness, in turn, facilitated changes in ASC behavior similar to those observed with tumor-derived chemical cues. Orthotopic mouse studies further confirmed the pathological relevance of ASCs in tumor progression and stiffness in vivo. In summary, altered ASC behavior can promote tumorigenesis and, thus, their implementation for regenerative therapy should be carefully considered in patients previously treated for cancer.
Abstract Determining the depth dependence of the shear properties of articular cartilage is essential for understanding the structure–function relation in this tissue. Here, we measured spatial ...variations in the shear modulus G of bovine articular cartilage using a novel technique that combines shear testing, confocal imaging and force measurement. We found that G varied by up to two orders of magnitude across a single sample, exhibited a global minimum 50–250 μm below the articular surface in a region just below the superficial zone and was roughly constant at depths >1000 μm (the “plateau region”). For plateau strains γplateau ≈0.75% and overall compressive strains ε ≈5%, Gmin and Gplateau were ≈70 and ≈650 kPa, respectively. In addition, we found that the shear modulus profile depended strongly on the applied shear and axial strains. The greatest change in G occurred at the global minimum where the tissue was highly nonlinear, stiffening under increased shear strain, and weakening under increased compressive strain. Our results can be explained through a simple thought model describing the observed nonlinear behavior in terms of localized buckling of collagen fibers and suggest that compression may decrease the vulnerability of articular cartilage to shear-induced damage by lowering the effective strain on individual collagen fibrils.
Objective To evaluate the clinical safety of antenatal and postnatal N-acetylcysteine (NAC) as a neuroprotective agent in maternal chorioamnionitis in a randomized, controlled, double-blinded trial. ...Study design Twenty-two mothers >24 weeks gestation presenting within 4 hours of diagnosis of clinical chorioamnionitis were randomized with their 24 infants to NAC or saline treatment. Antenatal NAC (100 mg/kg/dose) or saline was given intravenously every 6 hours until delivery. Postnatally, NAC (12.5-25 mg/kg/dose, n = 12) or saline (n = 12) was given every 12 hours for 5 doses. Doppler studies of fetal umbilical and fetal and infant cerebral blood flow, cranial ultrasounds, echocardiograms, cerebral oxygenation, electroencephalograms, and serum cytokines were evaluated before and after treatment, and 12, 24, and 48 hours after birth. Magnetic resonance spectroscopy and diffusion imaging were performed at term age equivalent. Development was followed for cerebral palsy or autism to 4 years of age. Results Cardiovascular measures, cerebral blood flow velocity and vascular resistance, and cerebral oxygenation did not differ between treatment groups. Cerebrovascular coupling was disrupted in infants with chorioamnionitis treated with saline but preserved in infants treated with NAC, suggesting improved vascular regulation in the presence of neuroinflammation. Infants treated with NAC had higher serum anti-inflammatory interleukin-1 receptor antagonist and lower proinflammatory vascular endothelial growth factor over time vs controls. No adverse events related to NAC administration were noted. Conclusions In this cohort of newborns exposed to chorioamnionitis, antenatal and postnatal NAC was safe, preserved cerebrovascular regulation, and increased an anti-inflammatory neuroprotective protein. Trial registration ClinicalTrials.gov : NCT00724594.
Chylothorax is a well-described complication after cardiothoracic surgery in children. Medical nutritional therapy for chylothorax includes medium-chain triglyceride (MCT) formulas and reduction in ...enteral long-chain triglyceride intake to reduce chyle production. Human milk is usually eliminated from the diet of infants with chylothorax because of its high long-chain triglyceride content. However, given the immunologic properties of human milk, young infants with chylothorax may benefit from using human milk over human milk substitutes. We performed a retrospective cohort study to describe the feasibility and efficacy of defatted human milk (DHM) for the treatment for chylothorax in infants after cardiac surgery and to compare growth outcomes between infants treated with DHM (
n
= 14) versus MCT formula (
n
= 21). There were no differences in mortality or length of hospital stay between the DHM and MCT formula treatment groups. The DHM treatment group had a significantly higher weight-for-age
z
-score at hospital discharge compared to the MCT formula group with median
z
-scores of −1 (−2 to 0.5) and −1.5 (−2 to 0), respectively (
p
= 0.02). In infants with chylothorax after cardiac surgery, DHM is a safe and feasible medical nutritional treatment and may have potential benefits for improved nutrition and growth.
Truncus arteriosus repair is associated with higher morbidity and mortality compared with many other congenital heart operations. We sought to determine factors associated with mortality and adverse ...outcomes in infants undergoing truncus arteriosus repair.
We used the Pediatric Health Information System Database to identify infants aged < 90 days who underwent truncus arteriosus repair from 2004 to 2019. The primary outcome was hospital mortality. Secondary outcomes were prolonged postoperative length of stay (>30 days) and hospital readmission within 90 days. Multivariable logistic regression models were used to identify associated factors for adverse outcomes.
A total of 1645 subjects were included. Hospital mortality occurred in 164 (10%). Factors independently associated with mortality included birth weight < 3 kg, admit age < 48 hours, truncal valve surgery, cardiac arrest, extracorporeal membrane oxygenation, acute kidney injury, cardiac catheterization, tracheostomy, and earlier era. Prolonged postoperative length of stay occurred in 508 patients (31%). Factors independently associated with prolonged postoperative length of stay included prematurity, DiGeorge syndrome, admit age < 48 hours, later surgical era, acute kidney injury, infection, cardiac catheterization, vocal cord paralysis, tracheostomy, and gastrostomy. Readmission within 90 days occurred in 511 of 1481 surviving patients (34%). DiGeorge syndrome, cleft lip/palate, cardiac catheterization, and extracorporeal membrane oxygenation were factors independently associated with hospital readmission.
We identified multiple factors associated with hospital mortality and adverse outcomes in infants undergoing truncus arteriosus repair. This information is useful for quality improvement initiatives, perioperative counseling, and discharge planning.
The efficacy of intraoperative corticosteroids to improve outcomes following congenital cardiac operations remains controversial.
The purpose of this study was to determine whether intraoperative ...methylprednisolone improves post-operative recovery in neonates undergoing cardiac surgery.
Neonates undergoing cardiac surgery with cardiopulmonary bypass at 2 centers were enrolled in a double-blind randomized controlled trial of methylprednisolone (30 mg/kg) or placebo after the induction of anesthesia. The primary outcome was a previously validated morbidity-mortality composite that included any of the following events following surgery before discharge: death, mechanical circulatory support, cardiac arrest, hepatic injury, renal injury, or rising lactate level (>5 mmol/l).
Of the 190 subjects enrolled, 176 (n = 81 methylprednisolone, n = 95 placebo) were included in this analysis. A total of 27 (33%) subjects in the methylprednisolone group and 40 (42%) in the placebo group reached the primary study endpoint (odds ratio OR: 0.63; 95% confidence interval CI: 0.31 to 1.3; p = 0.21). Methylprednisolone was associated with reductions in vasoactive inotropic requirements and in the incidence of the composite endpoint in subjects undergoing palliative operations (OR: 0.38; 95% CI: 0.15 to 0.99; p = 0.048). There was a significant interaction between treatment effect and center. In this analysis, methylprednisolone was protective at 1 center, with an OR: 0.35 (95% CI: 0.15 to 0.84; p = 0.02), and not so at the other center, with OR: 5.13 (95% CI: 0.85 to 30.90; p = 0.07).
Intraoperative methylprednisolone failed to show an overall significant benefit on the incidence of the composite primary study endpoint. There was, however, a benefit in patients undergoing palliative procedures and a significant interaction between treatment effect and center, suggesting that there may be center or patient characteristics that make prophylactic methylprednisolone beneficial.
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