Exogenous nitric oxide delivery protects against cardiopulmonary bypass-associated acute kidney injury: Histologic and serologic evidence from an ovine model.

OBJECTIVE: Several human studies have associated nitric oxide administration via the cardiopulmonary bypass circuit with decreased incidence of cardiopulmonary bypass-associated acute kidney injury, but histopathologic and serologic evidence of nitric oxide efficacy for acute kidney injury attenuation are lacking. METHODS: By using a survival ovine model (72 hours), acute kidney injury was induced by implementing low-flow cardiopulmonary bypass for 2 hours, followed by full-flow cardiopulmonary bypass for 2 hours. The nitric oxide cohort (n = 6) received exogenous nitric oxide through the cardiopulmonary bypass circuit via the oxygenator, and the control group (n = 5) received no nitric oxide. Serial serologic biomarkers and renal histopathology were obtained. RESULTS: Baseline characteristics (age, weight) and intraoperative parameters (cardiopulmonary bypass time, urine output, heart rate, arterial pH, and lactate) were equivalent (P > .10) between groups. Postoperatively, urine output, heart rate, respiratory rate, and peripheral arterial saturation were equivalent (P > .10) between groups. Post-cardiopulmonary bypass creatinine elevations from baseline were significantly greater in the control group versus the nitric oxide group at 16, 24, and 48 hours (all P < .05). Histopathologic evidence of moderate/severe acute kidney injury (epithelial necrosis, tubular slough, cast formation, glomerular edema) occurred in 60% (3/5) of the control group versus 0% (0/6) of the nitric oxide group. Cortical tubular epithelial cilia lengthening (a sensitive sign of cellular injury) was significantly greater in the control group than in the nitric oxide group (P = .012). CONCLUSIONS: In a survival ovine cardiopulmonary bypass model, nitric oxide administered with cardiopulmonary bypass demonstrated serologic and histologic evidence of renal protection from acute kidney injury. These results provide insight into 1 potential mechanism for cardiopulmonary bypass-associated acute kidney injury and supports continued study of nitric oxide via cardiopulmonary bypass circuit for prevention of acute kidney injury.

Palliated Hypoplastic Left Heart Syndrome Patients Experience Superior Waitlist and Comparable Post-Heart Transplant Survival to Non-Single Ventricle Congenital Heart Disease Patients.

Congenital heart disease (CHD) is a well-established risk factor for inferior waitlist and post-heart transplant survival in children. Differences in outcomes between CHD subgroups are understudied. The present study compared outcomes for palliated hypoplastic left heart syndrome (HLHS) patients to other non-single ventricle CHD (non-SVCHD) and non-CHD patients. United Network for Organ Sharing was used to identify children (age < 18) listed for heart transplant in the United States between 2016 and 2021. CHD sub-diagnoses were only available for United Network for Organ Sharing status 1a after 2015, thereby defining the cohort. Waitlist outcomes were studied using competing-risk time-to-event analysis for transplantation, mortality/decompensation, and alive-on-waitlist. Multivariable Cox proportional hazards regression analyses were used to identify factors associated with inferior post-transplant survival. Patients included: palliated-HLHS (n = 477), non-SVCHD (n = 686), and non-CHD (n = 1261). At listing, Palliated-HLHS patients were older than non-SVCHD (median 2-year [IQR 0-8] vs median 0-year [0-3], respectively) and younger than non-CHD (median 7-year [0-14]) (P < 0.001 vs both), and were more likely to be white (P < 0.01 vs both). Upon time-to-event analysis, rates of waitlist mortality/decompensation rates were greater among non-SVCHD than palliated-HLHS. Post-transplant survival was comparable between palliated-HLHS and non-SVCHD (P = 0.920) but worse compared to non-CHD (P < 0.001). Both palliated-HLHS (HR 2.40 [95% CI 1.68-3.42]) and non-SVSCHD (2.04 [1.39-2.99]) were independently associated with post-transplant mortality. Palliated-HLHS patients with heart failure experience significantly worse post-transplant outcomes than non-CHD but, compared to other CHD patients, experience superior waitlist and comparable post-transplant survival. While a high-risk cohort, HLHS patients can achieve gratifying waitlist and post-transplant survival.

Barriers in surgical research: A perspective from the developing world.

Research in surgery has led to significant advances over the last century in terms of how medicine is practised in and outside the operating rooms today. Surgical research in the developed countries is responsible for most of this advancement, but it is often inapplicable in resource-limited settings in the developing world. Lower- and middle-income countries are in a unique position to take this work further, but they are limited by certain barriers. These barriers could broadly be classified under social and cultural, infrastructure, financial, ethical, and personal categories. These barriers are often not fully realised, but can potentially be addressed with concerted efforts to continue the advancement of medicine for everyone.

Identifying prenatal ultrasound predictors and the ideal neonatal management of closing gastroschisis: the key is prevention.

OBJECTIVE: To evaluate the optimal approaches to initial surgical management and the potential for prenatal ultrasound detection of patients with closing gastroschisis. STUDY DESIGN: We performed a retrospective analysis of patients born with gastroschisis to determine clinical and surgical outcomes and the ability to determine prognosis by prenatal imaging. Data collected included operative findings and postoperative outcome, as well as prenatal imaging features from a subset of cases with and without closing gastroschisis. Statistical analyses were performed as appropriate. RESULTS: We included 197 patients with gastroschisis. No statistical significance was seen in outcomes between closing gastroschisis patients undergoing resection versus intracorporeal parking (n = 18). Ultrasound review was performed on 33 of these patients, 11 with closing gastroschisis, and 22 without. Significantly more closing gastroschisis patients had imaging indicative of progressive defect narrowing and defect diameter ≤8 mm after 30 weeks of gestation versus non-closing patients (p = 0.002). CONCLUSION: Parking of extruded bowel offers potential for intestinal remodeling. In addition, prenatal ultrasound may be useful in detection of closing gastroschisis in utero.

Reintervention After Infant Aortic Arch Repair Using a Tailored Autologous Pericardial Patch.

BACKGROUND: Aortic arch reobstruction is a common complication after aortic repair, with rates of reintervention varying from 0% to 40%, depending on the disease and the institution. This study aimed to determine the reintervention rate in children undergoing aortic arch repair using a tailored autologous pericardial patch at our center (Monroe Carell, Jr Children's Hospital at Vanderbilt, Nashville, TN). METHODS: This retrospective study examined all patients operated on by a single surgeon for aortic arch reconstruction through sternotomy, from 2011 to 2018, with 1 year of follow-up. Our data set was analyzed for normality by using the Shapiro-Wilk test, and nonparametric statistical methods were used. Kaplan-Meier survival analysis was performed, IBM SPSS software version 23 was used to perform all statistical analysis. RESULTS: A total of 171 patients met inclusion criteria. Twenty-three (13.5%) patients underwent aortic arch reinterventions during the study period, 17 (9.9%) catheter based and 3 (1.8%) surgical. Three patients (1.8%) had both. Freedom from reintervention at 1-year follow-up for the univentricular and biventricular patients was 82.1% and 89.4% (P = .174), respectively. To assess the growth of the aortic arch over time, cardiac catheterization measurements were used to index different parts of the aortic arch against the descending aorta. Ascending-to-descending aortic arch measurements revealed that the pre-Glenn median was 2.0 (interquartile range, 1.8 to 2.2), whereas the pre-Fontan median was 2.5 (interquartile range, 2.2 to 2.7) (P < .05). CONCLUSIONS: There was no significant difference in reintervention rates between biventricular and univentricular arches, and catheterization measurements showed significant growth of the arch over time. The use of a tailored autologous pericardial patch for aortic arch repair is comparable to other reported methods of arch repair.

An in silico approach to analyze HCV genotype-specific binding-site variation and its effect on drug-protein interaction.

Genotype variation in viruses can affect the response of antiviral treatment. Several studies have established approaches to determine genotype-specific variations; however, analyses to determine the effect of these variations on drug-protein interactions remain unraveled. We present an in-silico approach to explore genotype-specific variations and their effect on drug-protein interaction. We have used HCV NS3 helicase and fluoroquinolones as a model for drug-protein interaction and have investigated the effect of amino acid variations in HCV NS3 of genotype 1a, 1b, 2b and 3a on NS3-fluoroquinolone interaction. We retrieved 687, 667, 101 and 248 nucleotide sequences of HCV NS3 genotypes 1a, 1b, 2b, and 3a, respectively, and translated these into amino acid sequences and used for genotype variation analysis, and also to construct 3D protein models for 2b and 3a genotypes. For 1a and 1b, crystal structures were used. Drug-protein interactions were determined using molecular docking analyses. Our results revealed that individual genotype-specific HCV NS3 showed substantial sequence heterogeneity that resulted in variations in docking interactions. We believe that our approach can be extrapolated to include other viruses to study the clinical significance of genotype-specific variations in drug-protein interactions.

Transdiaphragmatic tunneled Broviac catheters: Cost-effective perioperative central venous access in infants undergoing cardiac surgery.

OBJECTIVES: Infants undergoing congenital heart surgery require central venous lines which can be achieved by various combinations of transthoracic lines, percutaneous-indwelling central catheters and tunneled Broviac catheters. Transthoracic lines are removed by protocol prior to cardiac intensive care unit discharge (risk of bleeding), at which time percutaneous-indwelling central catheters are placed. Transdiaphragmatic tunneled Broviac catheters placed at the time of sternotomy, remain in place until hospital discharge, when they are safely removed at bedside. We characterized actual cost profiles associated with strategies that do versus do not include tunneled Broviac catheters. METHODS: From January 2014 to December 2016, we identified a study population of 220 consecutive patients under 1 year of age undergoing congenital heart surgery. Cost data were acquired from our electronic patient system interface database and office of finance. Our cohort was divided into 2 groups, tunneled Broviac catheter and nontunneled Broviac catheter. We calculated the total cost associated with each groups' central venous lines, propensity matched, and used the Mann-Whitney U test to analyze the results. RESULTS: Eighty-three (37.7%) of the 220 patients had tunneled Broviac catheters. The tunneled Broviac catheter group had 4 percutaneous-indwelling central catheter insertions and 6 radiological interventions while the nontunneled Broviac catheter group had 90 percutaneous-indwelling central catheters and 203 radiologic interventions. After propensity score matching, both groups were reduced to 82 patients and sum, median and interquartile range cost for tunneled Broviac catheters and nontunneled Broviac catheters was $17,351.84, $159.76 (128-159.76) versus $72,809.32, $1277.26 (31.76-1277.26), P < .02 respectively. CONCLUSIONS: Tunneled Broviac catheters, placed routinely at cardiac surgery, incur lower costs than the conventional combination of transthoracic lines and percutaneous-indwelling central catheters. The cost-effectiveness is achieved by reducing the number of percutaneous-indwelling central catheters and associated radiologic interventions.

Sedated Echocardiograms Better Characterize Branch Pulmonary Arteries Following Bidirectional Glenn Palliation with Minimal Risk of Adverse Events.

Patients post-bidirectional Glenn (BDG) operation are at risk of left and right pulmonary artery (LPA and RPA) hypoplasia. Transthoracic echocardiograms (TTE) in active children can miss essential elements of anatomy. Procedural sedation improves image quality but increases risk of adverse events. We hypothesized that echocardiograms performed with sedation in patients post-BDG would improve visualization of branch pulmonary arteries with minimal adverse events. Patients post-BDG between 2007-2016 were identified. Exclusion criteria were > 12 months of age, absence of complete TTE before discharge, death before discharge, conversion to shunt physiology, and prolonged post-operative course > 7 weeks. Of 254 post-BDG patients, 153 met inclusion/exclusion criteria. TTE reports were reviewed for visualization of LPA/RPA and hypoplasia of LPA/RPA. Blinded assessment of image quality was performed (scale of 1[poor] to 5[excellent]). Pertinent clinical data were recorded. Pearson's chi-squared and Wilcoxon Rank Sum tests used for statistical analysis. The median age at surgery and hospital stay were 4.8 months and 10 days. Twenty-three patients underwent sedated TTE (15%). Sedated TTE significantly improved visualization of the RPA (100% vs 82%, p = 0.029) and LPA, though this did not reach statistical significance (100% vs 91%, p = 0.129). Sedated TTEs has significantly better image quality (median of 4 vs 3, p < 0.001). There were no serious adverse events due to sedation. Sedated TTE early post-BDG is safe, improves visualization of the RPA and LPA, and improves overall image quality. Routine sedated TTE in these patients should be considered. Implications for long-term outcome need to be further analyzed.

Donor considerations in pediatric heart transplantation.

Donors for pediatric heart transplantation are accepted based on variety of donor factors. There is wide variability in practice across centers and lack of evidence to guide standardized approach for some donor characteristics. This article reviews current practice and evidence for donor evaluation in pediatric heart transplantation.

Development and Implementation of an Inexpensive, Easily Producible, Time Efficient External Ventricular Drain Simulator Using 3-Dimensional Printing and Image Registration.

BACKGROUND: External ventricular drain (EVD) placement is one of the most commonly performed procedures in neurosurgery, frequently by the junior neurosurgery resident. Simulators for EVD placement are often costly, time-intensive to create, and complicated to set up. OBJECTIVE: To describe creation of a simulator that is inexpensive, time-efficient, and simple to set up. METHODS: This simulator involves printing a hollow head using a desktop 3-dimensional (3D) printer. This head is registered to a commercially available image-guidance system. A total of 11 participants volunteered for this simulation module. EVD placement was assessed at baseline, after verbal teaching, and after live 3D view instruction. RESULTS: Accurate placement of an EVD on the right side at the foramen of Monro or the frontal horn of the lateral ventricle increased from 44% to 98% with training. Similarly, accurate placement on the left increased from 42% to 85% with training. CONCLUSION: During participation in the simulation, accurate placement of EVDs increased significantly. All participants believed that they had a better understanding of ventricular anatomy and that this module would be useful as a teaching tool for neurosurgery interns.

Direct Splanchnic Perfusion Safely Avoids Deep Hypothermia.

Deep hypothermia for the operative correction of congenital cardiac lesions protects hypoperfused organs, mostly because of its effect on lowering metabolic demand and oxygen requirement. Deleterious cerebral and extracranial side effects of deep hypothermia itself calls for a reexamination of the therapeutic value of hypothermia, and has led to the development of alternative perfusion strategies. Here we describe the potential advantages of milder hypothermia over deep hypothermia and our method of a practical and reproducible implementation of multisite perfusion under mild hypothermia (32°C).

A Medium-Term Venous Access Alternative for Infants Undergoing Congenital Heart Surgery.

We describe a strategy aimed at maximizing the safety and minimizing the thrombogenicity of central venous lines for neonates with congenital heart defects. Our method involves the use of a tunneled technique to place a 4.2 Fr single-lumen (Broviac) catheter in the subpericardial space, with minimal intravascular course and a tip placed in the lower right atrium. Using this technique, we potentially eliminated the requirement for percutaneous placement of central venous lines postoperatively as well as potentially decreased the risk of intrapericardial bleeding associated with transthoracic lines.

Evolution of a level I pediatric trauma center: Changes in injury mechanisms and improved outcomes.

BACKGROUND: Trauma is the leading cause of mortality among children, underscoring the need for specialized child-centered care. The impact on presenting mechanisms of injury and outcomes during the evolution of independent pediatric trauma centers is unknown. The aim of this study was to evaluate the impact of our single center transition from an adult to American College of Surgeons-verified pediatric trauma center. METHODS: A retrospective analysis was performed of 1,190 children who presented as level I trauma activations between 2005 and 2016. Patients were divided into 3 chronological treatment eras: adult trauma center, early pediatric trauma center, and late pediatric trauma center after American College of Surgeons verification review. Comparisons were made using Pearson χ2, Wilcoxon rank sum, and Kruskal-Wallis tests. RESULTS: The predominant mechanism of injury was motor vehicle crash, with increases noted in assault/abuse (2% adult trauma center, 11% late pediatric trauma center). A decrease in intensive care admissions was identified during late pediatric trauma center compared with early pediatric trauma center and adult trauma center (51% vs 62.4% vs 67%, P < .001), with concomitant increases in admissions to the floor and immediate operative interventions, but overall mortality was unchanged. CONCLUSION: Transition to a verified pediatric trauma center maintains the safety expected of the American College of Surgeons certification, but with notable changes identified in mechanism of injury and improvements in resource utilization.

Bidirectional Inferior Cavopulmonary Anastomosis: Pre-Fontan Interim Palliation.

We report a novel method of constructing an extracardiac bidirectional inferior cavopulmonary anastomosis. Our patient was a 4-month-old girl with complex single-ventricle anatomy and a small-caliber superior vena cava. A direct anastomosis from the inferior vena cava to the main pulmonary artery was constructed by using all autologous tissue. The resulting pathway remained patent and exhibited growth with age. Furthermore, a pulmonary arteriovenous malformation did not develop. This case demonstrates how a bidirectional inferior cavopulmonary anastomosis is feasible in the human and can provide similar hemodynamic results as the bidirectional superior cavopulmonary anastomosis.

Neonatal Aortic Arch Reconstruction With Direct Splanchnic Perfusion Avoids Deep Hypothermia.

BACKGROUND: Neonatal aortic arch reconstruction, typically performed with deep hypothermia and selective cerebral perfusion, leaves splanchnic organ protection dependent on hypothermia alone. A simplified method of direct in-field descending aortic perfusion during neonatal arch reconstruction permits the avoidance of deep hypothermia. We hypothesize that direct splanchnic perfusion at mild hypothermia provides improved or equivalent safety compared with deep hypothermia and may contribute to postoperative extracardiac organ recovery. METHODS: Included were 138 biventricular patients aged younger than 90 days undergoing aortic arch reconstruction with cardiopulmonary bypass. Patients were grouped according to perfusion method A (selective cerebral perfusion with deep hyperthermia at 18° to 20°C) or method B (selective cerebral perfusion and splanchnic perfusion at 30° to 32°C). Patient characteristics and perioperative clinical and serologic data were analyzed. Significance was assigned for p of less than 0.05. RESULTS: Of the 138 survivors, 63 underwent method A and 75 underwent method B. The median age at operation was 8.5 days (range, 6 to 15 days), and median weight was 3.2 kg (range, 2.8 to 3.73 kg), with no significant differences between groups. Cardiopulmonary bypass times were comparable between the two perfusion methods (p = 0.255) as were the ascending aortic cross-clamp times (p = 0.737). The postoperative glomerular filtration rate was significantly different between our groups (p = 0.028 to 0.044), with method B achieving a higher glomerular filtration rate. No significant differences were seen in ventilator time, postoperative length of stay, fractional increase of postoperative serum creatinine over preoperative serum creatinine, and postoperative lactate. CONCLUSIONS: A simplified method of direct splanchnic perfusion during neonatal aortic arch reconstruction avoids the use of deep hypothermia and provides renal protection at least as effective as deep hypothermia.