Standardizing Prostaglandin Initiation in Prenatally Diagnosed Ductal-Dependent Neonates; A Quality Initiative.

Prostaglandin E1 (PGE) is used in patients with ductal-dependent congenital heart disease (CHD). Side effects of apnea and fever are often dose dependent and occur within 48 h after initiation. We initiated a standardized approach to PGE initiation after our institution recognized a high incidence of side effects and a wide variety of starting doses of PGE. Neonates with prenatally diagnosed ductal-dependent CHD were identified, started on a standardized protocol that started PGE at 0.01 mcg/kg/min, and evaluated for PGE related side effects. Compliance, outcomes and dose adjustments during the first 48 h post-PGE initiation were evaluated. Fifty patients were identified (25 pre-intervention; 25 post-intervention). After intervention, compliance with the protocol was 96%, and apnea or fever occurred in 28% (compared to 63% pre-intervention, p = 0.015). Dose adjustments (either increase or decrease) prior to cardiac surgery were similar in both cohorts (60%, 52%, p = 0.569). There were no mortalities or emergent procedures performed due to ductus arteriosus closure. Standardizing a protocol for initiating PGE in prenatally diagnosed ductal-dependent CHD was successful and reduced the incidence of apnea, fever, and sepsis evaluations. A starting dose of 0.01 mcg/kg/min did not cause increased adverse effects.

Gastrostomy tube placement in congenital cardiac surgery: a multi-institutional database study.

INTRODUCTION: Neonates and infants who undergo congenital cardiac surgery frequently have difficulty with feeding. The factors that predispose these patients to require a gastrostomy tube have not been well defined. We aimed to report the incidence and describe hospital outcomes and characteristics in neonates and infants undergoing congenital cardiac surgery who required gastrostomy tube placement. MATERIALS AND METHOD: A retrospective review was performed on patients undergoing congenital cardiac surgery between October 2015 and December 2020. Patients were identified by International Classification of Diseases 10th Revision codes, utilising the performance improvement database Vizient® Clinical Data Base, and stratified by age at admission: neonates (<1 month) and infants (1-12 months). Outcomes were compared and comparative analysis performed between admissions with and without gastrostomy tube placement. RESULTS: There were 11,793 admissions, 3519 (29.8%) neonates and 8274 (70.2%) infants. We found an increased incidence of gastrostomy tube placement in neonates as compared to infants following congenital cardiac surgery (23.1% versus 6%, p = <0.001). Outcomes in neonates and infants were similar with increased length of stay and cost in those requiring a gastrostomy tube. Gastrostomy tube placement was noted to be more likely in neonates and infants with upper airway anomalies, congenital abnormalities, hospital infections, and genetic abnormalities. DISCUSSION: Age at hospitalisation for congenital cardiac surgery is a definable risk factor for gastrostomy tube requirement. Additional factors contribute to gastrostomy tube placement and should be used when counselling families regarding the potential requirement of a gastrostomy tube.

Orthotopic heart transplant in a pediatric patient with mixed connective tissue disease.

BACKGROUND: Patients with autoimmune inflammatory syndromes such as mixed connective tissue disease (MCTD) and systemic lupus erythematosus have previously been considered marginal candidates for orthotopic heart transplant (OHT). METHODS: A retrospective chart review was completed for this case report. RESULTS: We present the case of an 11-year-old girl with known MCTD who developed congestive heart failure refractory to medical therapy and underwent OHT. CONCLUSIONS: Despite her autoimmune condition, this patient has not experienced antibody-mediated rejection post-transplant and her inflammatory symptoms have greatly improved.

Biaxial Murine Vaginal Remodeling With Reproductive Aging.

Higher reproductive age is associated with an increased risk of gestational diabetes, pre-eclampsia, and severe vaginal tearing during delivery. Further, menopause is associated with vaginal stiffening. However, the mechanical properties of the vagina during reproductive aging before the onset of menopause are unknown. Therefore, the first objective of this study was to quantify the biaxial mechanical properties of the nulliparous murine vagina with reproductive aging. Menopause is further associated with a decrease in elastic fiber content, which may contribute to vaginal stiffening. Hence, our second objective was to determine the effect of elastic fiber disruption on the biaxial vaginal mechanical properties. To accomplish this, vaginal samples from CD-1 mice aged 2-14 months underwent extension-inflation testing protocols (n = 64 total; n = 16/age group). Then, half of the samples were randomly allocated to undergo elastic fiber fragmentation via elastase digestion (n = 32 total; 8/age group) to evaluate the role of elastic fibers. The material stiffness increased with reproductive age in both the circumferential and axial directions within the control and elastase-treated vaginas. The vagina demonstrated anisotropic mechanical behavior, and anisotropy increased with age. In summary, vaginal remodeling with reproductive age included increased direction-dependent material stiffness, which further increased following elastic fiber disruption. Further work is needed to quantify vaginal remodeling during pregnancy and postpartum with reproductive aging to better understand how age-related vaginal remodeling may contribute to an increased risk of vaginal tearing.

Impaired cognitive flexibility and heightened urgency are associated with increased alcohol consumption in rodent models of excessive drinking.

Alcohol use disorder (AUD) is characterized by impairments in decision-making that can exist as stable traits or transient states. Cognitive inflexibility reflects an inability to update information that guides decision-making and is thought to contribute to the inability to abstain from drinking. While several studies have reported evidence of impaired cognitive flexibility following chronic alcohol exposure, evidence that a pre-existing impairment in cognitive flexibility is a heritable risk factor for AUD is scarce. Here, we found that cognitive flexibility was impaired in rodents selectively bred for excessive alcohol consumption (alcohol preferring (P) rats), on the attentional set-shifting task (ASST). Further, the degree of impairment is predictive of future ethanol consumption, thus suggesting that cognitive inflexibility is a stable trait capable of predisposing one for drinking. In a second set of experiments, we observed an impairment in the ability of P rats to use a previously learned rule to guide foraging in a simple discrimination task. Convergence across several behavioral measures suggested that this impairment reflected a state of heightened urgency that interfered with decision-making. A similar impairment on a simple discrimination task was observed in Wistar rats with a history of alcohol consumption. These findings indicate how trait and state variables-in this case, impaired cognitive flexibility and heightened urgency, respectively-may influence the risk for excessive drinking. Furthermore, our results suggest that cognitive inflexibility and urgency can exist as both risk factors for and the result of alcohol exposure.

Invasive Cardiac Procedures in Interstage Single Ventricle Patients in Emergent Hospitalizations.

Single ventricle congenital heart disease (SV CHD) patients are at risk of morbidity and mortality between the first and second palliative surgical procedures (interstage). When these patients present acutely they often require invasive intervention. This study sought to compare the outcomes and costs of elective and emergent invasive cardiac procedures for interstage patients. Retrospective review of discharge data from The Vizient Clinical Data Base/Resource Manager™, a national health care analytics platform. The database was queried for admissions from 10/2014 to 12/2017 for children 1-6 months old with ICD-9 or ICD-10 codes for SV CHD who underwent invasive cardiac procedures. Demographics, length of stay (LOS), complication rate, in-hospital mortality and direct costs were compared between elective and emergent admissions using t test or χ2, as appropriate. The three most frequently performed procedures were also compared. 871 admissions identified, with 141 (16%) emergent. Age of emergent admission was younger than elective (2.9 vs. 4 months p < 0.001). Emergent admissions including cardiac catheterization or superior cavo-pulmonary anastomosis had longer LOS (58.7 vs. 25.8 day, p < 0.001 and 54.8 vs .22.6 days, p < 0.001) and higher costs ($134,774 vs. $84,253, p = 0.013 and $158,679 vs. $81,899, p = 0.017). Emergent admissions for interstage SV CHD patients undergoing cardiac catheterization or superior cavo-pulmonary anastomosis are associated with longer LOS and higher direct costs, but with no differences in complications or mortality. These findings support aggressive interstage monitoring to minimize the need for emergent interventions for this fragile patient population.

Treatment of tricuspid regurgitation and para-ring leak in tetralogy of Fallot with oversized SAPIEN 3 valve-in-ring implantation.

A 40-year-old female with previously repaired tetralogy of Fallot had recurrent severe tricuspid regurgitation with a para-ring leak after annuloplasty ring placement. Because of multiple prior sternotomies and co-morbidities, she was not felt to be a surgical candidate. Percutaneous placement of an oversized SAPIEN 3 valve-in-ring in the tricuspid position successfully treated the regurgitation and para-ring leak.

Patients with single ventricle anatomy may respond better to octreotide therapy for chylothorax after congenital heart surgery.

BACKGROUND AND AIMS: Chylothorax (CTX) occurs in 3% to 6% of children after surgery for congenital heart disease with significant morbidity and mortality. Octreotide has been proposed as therapy, but there are no predictors of response. The objective of this study was to identify possible predictors of response to octreotide. METHODS: Single-center retrospective review of patients who developed CTX after cardiac surgery. Data collected included demographics, cardiac lesion, surgical data, hospital course, CTX volume and duration, and interventions for CTX. Patients who received octreotide as part of their therapy were compared to those who did not. RESULTS: A total of 1150 patients underwent 1455 cardiac surgeries with 67 (4.6%) episodes of CTX. Patients with CTX were younger, lower weight, more likely to undergo cardiopulmonary bypass, and had higher RACHS-1 scores and mortality. Nineteen patients with CTX received octreotide as part of their treatment and six (32%) had at least 50% reduction in CTX volume. Patients who responded to octreotide had lower CTX volume (18 mL/kg/day vs. 55 mL/kg/day, p=0.023) and a higher proportion of patients with single ventricle anatomy (67% vs. 18%, p=0.046). CONCLUSIONS: There is a subset of patients who seem to respond to octreotide, but they have lower CTX volume and may have already been improving before octreotide therapy. Patients with single ventricle anatomy seemed to respond to octreotide and may benefit from its use.

Remodeling of murine vaginal smooth muscle function with reproductive age and elastic fiber disruption.

Advanced maternal age during pregnancy is associated with increased risk of vaginal tearing during delivery and maladaptive postpartum healing. Although the underlying mechanisms of age-related vaginal injuries are not fully elucidated, changes in vaginal microstructure may contribute. Smooth muscle cells promote the contractile nature of the vagina and contribute to pelvic floor stability. While menopause is associated with decreased vaginal smooth muscle content, whether contractile changes occur before the onset of menopause remains unknown. Therefore, the first objective of this study was to quantify the active mechanical behavior of the murine vagina with age. Further, aging is associated with decreased vaginal elastin content. As such, the second objective was to determine if elastic fiber disruption alters vaginal contractility. Vaginal samples from mice aged 2-14 months were used in maximum contractility experiments and biaxial extension-inflation protocols. To evaluate the role of elastic fibers with age, half of the vaginal samples were randomly allocated to enzymatic elastic fiber disruption. Contractile potential decreased and vaginal material stiffness increased with age. These age-related changes in smooth muscle function may be due, in part, to changes in microstructural composition or contractile gene expression. Furthermore, elastic fiber disruption had a diminished effect on smooth muscle contractility in older mice. This suggests a decreased functional role of elastic fibers with age. Quantifying the age-dependent mechanical contribution of smooth muscle cells and elastic fibers to vaginal properties provides a first step towards better understanding how age-related changes in vaginal structure may contribute to tissue integrity and healing. STATEMENT OF SIGNIFICANCE: Advanced maternal age at the time of pregnancy is linked to increased risks of vaginal tearing during delivery, postpartum hemorrhaging, and the development of pelvic floor disorders. While the underlying causes of increased vaginal injuries with age and associated pathologies remain unclear, changes in vaginal microstructure, such as elastic fibers and smooth muscle cells, may contribute. Menopause is associated with fragmented elastic fibers and decreased smooth muscle content; however, how reproductive aging affects changes in the vaginal composition and the mechanical properties remains unknown. Quantifying the mechanical contribution of smooth muscle cells and elastic fibers to vaginal properties with age will advance understanding of the potential structural causes of age-related changes to tissue integrity and healing.

Neural basis of cognitive control signals in anterior cingulate cortex during delay discounting.

Cognitive control involves allocating cognitive effort according to internal needs and task demands and the Anterior Cingulate Cortex (ACC) is hypothesized to play a central role in this process. We investigated the neural basis of cognitive control in the ACC of rats performing an adjusting-amount delay discounting task. Decision-making in this this task can be guided by using either a lever-value tracking strategy, requiring a 'resource-based' form of cognitive effort or a lever-biased strategy requiring a 'resistance-based' form of cognitive effort. We found that ACC ensembles always tightly tracked lever value on each trial, indicative of a resource-based control signal. These signals were prevalent in the neural recordings and were influenced by the delay. A shorter delay was associated with devaluing of the immediate option and a longer delay was associated with overvaluing of the immediate option. In addition, ACC theta (6-12Hz) oscillations were observed at the choice point of rats exhibiting a resistance-based strategy. These data provide candidates of neural activity patterns in the ACC that underlie the use of 'resource-based' and 'resistance-based' cognitive effort. Furthermore, these data illustrate how strategies can be engaged under different conditions in individual subjects.

Flexible coding schemes in dorsomedial prefrontal cortex underlie decision-making during delay discounting.

Determining how an agent decides between a small, immediate versus a larger, delayed reward has provided insight into the psychological and neural basis of decision-making. The tendency to excessively discount the value of delayed rewards is thought to reflect deficits in brain regions critical for impulse control such as the prefrontal cortex (PFC). This study tested the hypothesis that dorsomedial PFC (dmPFC) is critically involved in flexibly managing neural representations of strategies that limit impulsive choices. Optogenetic silencing of neurons in the rat dmPFC increased impulsive choices at an 8 sec, but not 4 sec, delay. Neural recordings from dmPFC ensembles revealed that, at the 8-sec delay, the encoding landscape transitions to reflect a deliberative-like process rather than the schema-like processes observed at the 4-sec delay. These findings show that changes in the encoding landscape reflect changes in task demands and that dmPFC is uniquely involved in decisions requiring deliberation.

Early aspirin use and the development of cardiac allograft vasculopathy in pediatric heart transplant recipients: A pediatric heart transplant society analysis.

BACKGROUND: Cardiac allograft vasculopathy (CAV) remains a leading cause of graft loss in pediatric heart transplant (HTx) recipients. Adult literature suggests that aspirin (ASA) use in the early post-HTx period may reduce the risk of CAV. This study aimed to determine the impact of early ASA use on the development of CAV in pediatric HTx recipients. METHODS: All subjects <17 years of age at time of primary HTx who survived ≥3 years without evidence of CAV were identified for inclusion from the Pediatric Heart Transplant Society database (1996-2019). Early ASA use was defined as ASA started within the first 3 years post-HTx and was classified as continuous or intermittent. Frequency of ASA use was described across centers. Kaplan-Meier method assessed freedom from CAV and overall graft survival. Multiphase parametric hazard analyses and propensity score matched analysis were used to identify independent risk factors. RESULTS: 3,011 patients were included with 387 (13%) receiving continuous ASA, 676 (22%) receiving intermittent ASA, and 1,948 (65%) receiving no ASA. ASA use was highly variable across centers (0%-100%). At baseline patients receiving continuous ASA therapy demonstrated inferior graft survival (p < 0.001) and worse freedom from CAV (p = 0.002), but with lower CAV grades (p = 0.05). In multiphase parametric hazard modeling continuous ASA use was not independently associated with CAV, but remained associated with inferior graft survival. Propensity-matched sub-analysis between continuous and no ASA groups demonstrated no difference in freedom from CAV or overall graft loss. CONCLUSIONS: ASA use varies widely across pediatric HTx centers. Early ASA use did not reduce the risk of CAV or graft loss in pediatric heart transplant recipients.

Cardiac Concerns in the Pediatric Athlete.

Cardiovascular disease remains the number one cause of death in Americans. It is no secret that exercise mitigates this risk. Exercise and regular physical activity are beneficial for physical health including aerobic conditioning, endurance, strength, mental health, and overall improved quality of life. Unfortunately, today many children and adolescents are sedentary, lacking the recommended daily amount of physical activity, leading to higher rates of obesity, cardiovascular disease, stroke, diabetes, anxiety, and depression. Given this rising concern, the World Health Organization launched a 12-year plan to improve physical activity in children and adolescents by reducing the inactivity rate by 15% in the world. How does this apply to children and adolescents with acquired or congenital heart disease?.

Patient Chief Complaint and Otolaryngology Referral Rationale: Discordance and Opportunities for Quality Improvement.

OBJECTIVE: As medical systems focus on patient satisfaction as an important care outcome, specialty clinics are tasked with continued improvement of patients' experience. When patient expectations for a consultation differ from that of the specialty provider, dissatisfaction with the experience can occur. One source of differing expectations is discordance between the patient's chief complaint and the clinical rationale for the consultation as requested by the referring provider. We sought to better understand when this discordance occurs, as well as factors contributing to this disorientation of patient and provider expectations in a safety net otolaryngology practice. METHODS: A retrospective observational study was performed and records were examined from new patient consultations. Patient questionnaires, including self-reported chief concerns, were compared with the electronic referral documentation. A difference between the patient's Chief Complaint (CC) and Referral Reason (RR) was defined as CC-RR Discordance. Medical records, pre-consultation patient communication, and scheduling data were also reviewed to evaluate contributing factors. RESULTS: Of the 1155 consultations examined, 952 were included in the analysis. A CC-RR Discordance was found in 175 (18.4%) of new-patient encounters, including 117 (12.3%) that were unable to articulate a CC (unsure of the reason for the appointment), and 58 (6.1%) that stated a CC that was different than the RR. The rate of CC-RR Discordance was higher in patients with female sex (P < .05), older age (P < .001), and longer time intervals between referral and appointment (P < .05). Lack of communication with the patient (instructions or referral notification) by the referring provider was not associated with CC-RR Discordance. CONCLUSIONS: Discordance between patient CC and the rationale for a consultation is common in this safety-net otolaryngology practice and may be an important source of patient dissatisfaction. Future opportunities for quality improvement include pre-consultation communication between the specialist and the patient and reducing time intervals between referral and appointment.

Increased risk of intraventricular hemorrhage in low birth weight infants with aortic coarctation.

Objective: To determine if there is an association between aortic coarctation (CoA) and intraventricular hemorrhage (IVH) in low birth weight (LBW) infants that may justify earlier intervention. While there is an increasing number of reports of successful early CoA intervention in LBW infants, there are no data to justify this approach.Material and methods: Retrospective review of the University Health System Consortium Clinical Data Base/Resource Manager, a national hospital discharge database. LBW (≤2 kg) infants, with and without IVH and isolated CoA were identified; IVH was stratified into low (grade 1 or 2) and high (grade 3 or 4) severity. Odds ratios were calculated for any, low and high-grade IVH with CoA.Results: Forty-six thousand and twenty LBW infants were identified; 3716 (8.1%) had IVH, 3001 (81%) with low, and 724 (19%) with high severity. Sixty-four infants had CoA, 13 had associated IVH (10 with low and three with high severity). The odds ratio for any IVH with CoA was 2.91 (95% CI 1.58-5.35), low severity 2.77 (95% CI 1.41-5.46) and high severity 3.45 (95% CI 1.07-11.07).Conclusions: In conclusion, this large retrospective database review found that LBW infants with CoA may be at increased risk of IVH. Further study is needed to determine if earlier catheter- or surgical-based intervention for CoA could reduce the risk of IVH in this population.

Preprocedural Imaging Evaluation of Pulmonary Valve Replacement After Repair of Tetralogy of Fallot: What the Radiologist Needs to Know.

Tetrallogy of Fallot (TOF) is the most frequent form of cyanotic congenital heart disease. Despite advances in surgical and medical treatment, mortality remains high. Residual dysfunction of the pulmonary valve (PV) after correction of right ventricular outflow tract obstruction is an important cause of morbidity, leading to irreversible right ventricular dysfunction, arrhythmias, heart failure and occasionally, death. The strategies for PVR have evolved over the last decades, and the timing of the intervention remains the foundation of the decision-making process. Symptoms of heart failure are unreliable indicators for optimal timing of repair. Imaging plays an essential role in the assessment of PV integrity and dysfunction. The identification of the best timing for PVR requires a multimodality approach. Transthoracic echocardiography is the most commonly used imaging modality for the initial assessment and follow-up of TOF patients, although its utility has technical limitations, especially in adults. Cardiac computed tomography and magnetic resonance imaging are now routinely used for preoperative and postoperative evaluation of these patients, and provide highly valuable information about the anatomy and pathophysiology. Imaging evidence of disease progression is now part of the major guidelines to define the best timing for reintervention. The purpose of this article is to review the pathophysiology after TOF repair, identify the main imaging anatomic and physiologic features, describe the indications for PVR and recognize the role of imaging in the assessment of these patients to define the appropriate timing of PVR.

Pelvic Organ Prolapse: A Review of In Vitro Testing of Pelvic Support Mechanisms.

Background: Pelvic organ prolapse (POP) affects a significant portion of the female population, impacting quality of life and often requiring intervention. The exact cause of prolapse is unknown. Methods: We review some of the current research that focuses on defining the elements involved in POP, with a focus on in vitro testing. Results: Treatment for POP, ranging from physical therapy or pessary use to more invasive surgery, has varying success rates. This variation is, in part, because the pathophysiology of pelvic floor support-and thus dysfunction-is incompletely understood, particularly regarding the structural components and biomechanical properties of tissue. However, researchers are working to identify and quantify the structural and functional dysfunction that may lead to the development of this condition. Conclusion: Given the limited understanding of prolapse development, more research is needed to quantify the microstructure of the pelvic organs and pelvic support structures, with and without prolapse. Identifying biomechanical properties in multiaxial configurations will improve our understanding of pelvic tissue support, as well as our ability to establish predictive models and improve clinical treatment strategies.

Catheter-associated bloodstream infection incidence and outcomes in congenital cardiac surgery.

OBJECTIVE: Catheter-associated bloodstream infections complicate and prolong hospitalizations. The incidence of catheter-associated bloodstream infections in children undergoing congenital cardiac surgery has not been reported. This study sought to define the incidence of catheter-associated bloodstream infections after congenital cardiac surgery in neonates and infants ≤12 months old and compare hospital outcomes and costs to those who underwent surgery and did not have a catheter-associated bloodstream infections. DESIGN: Retrospective review of hospital admissions between October 2013 and November 2015 for neonates and infants ≤12 months old at admission with ICD-9 codes for congenital cardiac surgery from discharge data from Vizient Clinical Data Base/Resource Manager (formerly University HealthSystem Consortium), an analytic platform for performance improvement. Hospitals were included if they had >100 congenital cardiac surgery admissions during the study period. Admissions were stratified by age at admission: Neonates (<1 month) and Infants (1-12 months). Established database flags for catheter-associated bloodstream infections were utilized. Length of stay, mortality, and direct costs were compared between admissions with and without catheter-associated bloodstream infections using t test or χ2 , as appropriate. RESULTS: Catheter-associated bloodstream infections incidence after congenital cardiac surgery was higher in Neonates than Infants (1.5 vs 0.8%, P = .024). Length of stay and direct costs were significantly higher for patients with catheter-associated bloodstream infections in both groups. Mortality was higher in the Infant group with catheter-associated bloodstream infections compared to those without catheter-associated bloodstream infections. CONCLUSIONS: Neonates develop catheter-associated bloodstream infections at nearly twice the rate of older infants. For those who develop infection, mortality is 2-8-fold greater and hospital costs are 4-6-fold higher, which further highlight the importance of catheter-associated bloodstream infections prevention in this population.

Production of Extracellular Matrix Fibers via Sacrificial Hollow Fiber Membrane Cell Culture.

Engineered scaffolds derived from extracellular matrix (ECM) have driven significant interest in medicine for their potential in expediting wound closure and healing. Extraction of extracellular matrix from fibrogenic cell cultures in vitro has potential for generation of ECM from human- and potentially patient-specific cell lines, minimizing the presence of xenogeneic epitopes which has hindered the clinical success of some existing ECM products. A significant challenge in in vitro production of ECM suitable for implantation is that ECM production by cell culture is typically of relatively low yield. In this work, protocols are described for the production of ECM by cells cultured within sacrificial hollow fiber membrane scaffolds. Hollow fiber membranes are cultured with fibroblast cell lines in a conventional cell medium and dissolved after cell culture to yield continuous threads of ECM. The resulting ECM fibers produced by this method can be decellularized and lyophilized, rendering it suitable for storage and implantation.