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Background: Nipple-sparing mastectomy (NSM) has become widely available for breast cancer prophylaxis. There are limited data on its long-term oncologic safety. The objective of this study was to determine the incidence of breast cancer in patients who underwent prophylactic NSM., Methods: All patients undergoing prophylactic NSM at a single institution from 2006 through 2019 were retrospectively reviewed. Patient demographic factors, genetic predispositions, mastectomy specimen pathology, and oncologic occurrences at follow-up were recorded. Descriptive statistics were performed where necessary to classify demographic factors and oncologic characteristics., Results: A total of 871 prophylactic NSMs were performed on 641 patients, with median follow-up of 82.0 months (standard error 1.24). A total of 94.4% of patients ( n = 605) underwent bilateral NSMs, although only the prophylactic mastectomy was considered. The majority of mastectomy specimens (69.6%) had no identifiable pathology. A total of 38 specimens (4.4%) had cancer identified in mastectomy specimens, with ductal carcinoma in situ being the most common (92.1%; n = 35). Multifocal or multicentric disease was observed in seven cases (18.4%) and lymphovascular invasion was identified in two (5.3%). One patient (0.16%), who was a BRCA2 variant carrier, was found to have breast cancer 6.5 years after prophylactic mastectomy., Conclusions: Overall primary oncologic occurrence rates are very low in high-risk patients undergoing prophylactic NSM. In addition to reducing the risk of oncologic occurrence, prophylactic surgery itself may be therapeutic in a small proportion of patients. Continued surveillance for these patients remains important to assess at longer follow-up intervals., Clinical Question/level of Evidence: Risk, IV., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Improvement in congenital heart disease (CHD) outcomes has created a growing population of adolescents and young adults with unique health needs that require thoughtful transition planning and eventual transfer of care to an adult provider. Often, poor health literacy and limited resources can lead to interrupted care, which places them at risk for adverse health-related consequences. In 2019, the Wisconsin Adult Congenital Heart Disease transition program partnered with Stanford Virtual Heart (SVH), a virtual reality (VR) platform, to allow young adult patients to learn about their CHD in a clinic-based setting. We completed a single-center pilot study to evaluate these patients' experience and perceptions to using VR during their transition education. At an initial transition visit, we used an immediate post-VR experience survey, scored using Likert scales of 1-5 (1 = strongly disagree, 5 = strongly agree). Twenty-two patients (13 males) between the ages of 16 and 19 participated. Lesions included pulmonary stenosis, Tetralogy of Fallot, atrial and ventricular septal defect, coarctation, aortic stenosis, hypoplastic left heart syndrome, and patent ductus arteriosus. Likert averages were 4.7 for finding VR helped with understanding their heart lesion, 4.6 for finding VR helped with understanding their heart surgery, 4.7 for enjoying the VR heart simulation, and 4.6 for finding that it was a good use of time. This study demonstrates that adolescents enjoyed using SVH and found it helpful. Clinical implementation shows promise as a plausible adjunct tool for transition education., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The transition from residency to paediatric cardiology fellowship is challenging due to the new knowledge and technical skills required. Online learning can be an effective didactic modality that can be widely accessed by trainees. We sought to evaluate the effectiveness of a paediatric cardiology Fellowship Online Preparatory Course prior to the start of fellowship., Methods: The Online Preparatory Course contained 18 online learning modules covering basic concepts in anatomy, auscultation, echocardiography, catheterisation, cardiovascular intensive care, electrophysiology, pulmonary hypertension, heart failure, and cardiac surgery. Each online learning module included an instructional video with pre-and post-video tests. Participants completed pre- and post-Online Preparatory Course knowledge-based exams and surveys. Pre- and post-Online Preparatory Course survey and knowledge-based examination results were compared via Wilcoxon sign and paired t-tests., Results: 151 incoming paediatric cardiology fellows from programmes across the USA participated in the 3 months prior to starting fellowship training between 2017 and 2019. There was significant improvement between pre- and post-video test scores for all 18 online learning modules. There was also significant improvement between pre- and post-Online Preparatory Course exam scores (PRE 43.6 ± 11% versus POST 60.3 ± 10%, p < 0.001). Comparing pre- and post-Online Preparatory Course surveys, there was a statistically significant improvement in the participants' comfort level in 35 of 36 (97%) assessment areas. Nearly all participants (98%) agreed or strongly agreed that the Online Preparatory Course was a valuable learning experience and helped alleviate some anxieties (77% agreed or strongly agreed) related to starting fellowship., Conclusion: An Online Preparatory Course prior to starting fellowship can provide a foundation of knowledge, decrease anxiety, and serve as an effective educational springboard for paediatric cardiology fellows.

Prophylactic nipple-sparing mastectomies (NSM) have become increasingly common, although there is little long-term data on its efficacy in prevention of breast cancer. The objective of this study was to assess the incidence of breast cancer in a cohort of patients undergoing prophylactic NSM with a median follow-up of 10 years., Methods: Patients receiving prophylactic NSM at a single institution from 2006 to 2019 were included in a retrospective nature. Patient demographics, genetic mutations, operative details, and specimen pathology were recorded, and all postoperative patient visits and documentation were screened for cancer occurrence. Descriptive statics were performed where appropriate., Results: Two hundred eighty-four prophylactic NSMs were performed on 228 patients with a median follow-up of 120.5 ± 15.7 months. Roughly, a third of patients had a known genetic mutation, with 21% BRCA1 and 12% BRCA2. The majority (73%) of prophylactic specimens had no abnormal pathology. The most commonly observed pathologies were atypical lobular hyperplasia (10%) and ductal carcinoma in situ (7%). Cancer was identified in 10% of specimens, with only one case of lymphovascular invasion. Thus far, there have been no incidences of locoregional breast cancer occurrence in this cohort., Conclusions: The long-term breast cancer occurrence rate in this cohort of prophylactic NSM patients at the time of this study is negligible. Despite this, continued surveillance of these patients is necessary until lifetime risk of occurrence following NSM has been established., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: Understanding how cardiovascular structure and physiology guide management is critically important in paediatric cardiology. However, few validated educational tools are available to assess trainee knowledge. To address this deficit, paediatric cardiologists and fellows from four institutions collaborated to develop a multimedia assessment tool for use with medical students and paediatric residents. This tool was developed in support of a novel 3-dimensional virtual reality curriculum created by our group., Methods: Educational domains were identified, and questions were iteratively developed by a group of clinicians from multiple centres to assess understanding of key concepts. To evaluate content validity, content experts completed the assessment and reviewed items, rating item relevance to educational domains using a 4-point Likert scale. An item-level content validity index was calculated for each question, and a scale-level content validity index was calculated for the assessment tool, with scores of ≥0.78 and ≥0.90, respectively, representing excellent content validity., Results: The mean content expert assessment score was 92% (range 88-97%). Two questions yielded ≤50% correct content expert answers. The item-level content validity index for 29 out of 32 questions was ≥0.78, and the scale-level content validity index was 0.92. Qualitative feedback included suggestions for future improvement. Questions with ≤50% content expert agreement and item-level content validity index scores <0.78 were removed, yielding a 27-question assessment tool., Conclusions: We describe a multi-centre effort to create and validate a multimedia assessment tool which may be implemented within paediatric trainee cardiology curricula. Future efforts may focus on content refinement and expansion to include additional educational domains.

Objectives: Virtual reality has emerged as a unique educational modality for medical trainees. However, incorporation of virtual reality curricula into formal training programmes has been limited. We describe a multi-centre effort to develop, implement, and evaluate the efficacy of a virtual reality curriculum for residents participating in paediatric cardiology rotations., Methods: A virtual reality software program ("The Stanford Virtual Heart") was utilised. Users are placed "inside the heart" and explore non-traditional views of cardiac anatomy. Modules for six common congenital heart lesions were developed, including narrative scripts. A prospective case-control study was performed involving three large paediatric residency programmes. From July 2018 to June 2019, trainees participating in an outpatient cardiology rotation completed a 27-question, validated assessment tool. From July 2019 to February 2020, trainees completed the virtual reality curriculum and assessment tool during their cardiology rotation. Qualitative feedback on the virtual reality experience was also gathered. Intervention and control group performances were compared using univariate analyses., Results: There were 80 trainees in the control group and 52 in the intervention group. Trainees in the intervention group achieved higher scores on the assessment (20.4 ± 2.9 versus 18.8 ± 3.8 out of 27 questions answered correctly, p = 0.01). Further analysis showed significant improvement in the intervention group for questions specifically testing visuospatial concepts. In total, 100% of users recommended integration of the programme into the residency curriculum., Conclusions: Virtual reality is an effective and well-received adjunct to clinical curricula for residents participating in paediatric cardiology rotations. Our results support continued virtual reality use and expansion to include other trainees.

Background: Venoarterial extracorporeal membrane oxygenation (ECMO) supports patients with advanced cardiac dysfunction; however, mortality occurs in a significant subset of patients. The authors performed a multicenter, prospective study to determine hemodynamic and echocardiographic predictors of mortality in children placed on ECMO for cardiac support., Methods: Over 8 years, six heart centers prospectively assessed echocardiographic and hemodynamic variables on full and minimum ECMO flow. Sixty-three patients were enrolled, ranging in age from 1 day to 16 years. Hemodynamic measurements included heart rate, vasoactive inotropic score, arteriovenous oxygen difference, pulse pressure, and lactate. Echocardiographic variables included shortening fraction, ejection fraction (EF), right ventricular fractional area change, outflow tract Doppler-derived stroke distance (velocity-time integral [VTI]), and degree of atrioventricular valve regurgitation. Patients were stratified into two groups: those who were able to wean within 48 hours of assessment and survived without ventricular assist devices or orthotopic heart transplantation (successful wean group) and those with unsuccessful weaning. For each patient, variables were compared between full and minimum ECMO flow for each group., Results: Thirty-eight patients (60%) formed the unsuccessful group (two with ventricular assist devices, four with orthotopic heart transplantation, 24 deaths), and 25 constituted the successful wean group. At minimum flow, higher EF (53 ± 16% vs 40 ± 20%, P = .0094), less mitral regurgitation (0.8 ± 0.9 vs 1.4 ± 0.9, P = .0329), and lower central venous pressure (12.0 ± 3.9 vs 14.7 ± 5.4 mm Hg), along with higher VTI (9.0 ± 2.9 vs 6.8 ± 3.7 cm, P = .0154), correlated successful weaning. A longer duration of ECMO (8 vs 5 days, P < .0002) was associated with unsuccessful weaning. Multivariate logistic regression predicted minimum-flow EF and VTI to independently predict successful weaning with cutoff values by receiver operating characteristic analysis of EF > 41% (area under the curve, 0.712; P = .0005) and VTI > 7.9 cm (area under the curve, 0.729; P = .0010)., Conclusions: Diminished VTI or EF during ECMO weaning predicts the need for orthotopic heart transplantation or ventricular assist device support or death in children on ECMO for cardiac dysfunction. Increased postwean central venous pressure or mitral regurgitation along with a prolonged ECMO course also predicted these adverse outcomes. These measurements should be used to help discriminate which patients will require alternative methods of circulatory support for survival., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Despite the increased use of nipple-sparing mastectomies, there are limited data examining long-term cancer recurrence rates in these patients. The objective of this study was to analyze breast cancer recurrence in patients who underwent therapeutic nipple-sparing mastectomy with a median of 10 years of follow-up., Methods: All patients undergoing nipple-sparing mastectomy at a single institution were retrospectively reviewed temporally to obtain a median of 10 years of follow-up. Patient demographic factors, mastectomy specimen pathologic findings, and oncologic outcomes were analyzed. Univariate analysis was performed to identify independent risk factors for locoregional recurrence., Results: One hundred twenty-six therapeutic nipple-sparing mastectomies were performed on 120 patients. The most frequently observed tumor histology included invasive ductal carcinoma (48.4 percent) and ductal carcinoma in situ (38.1 percent). Mean tumor size was 1.62 cm. Multifocal or multicentric disease and lymphovascular invasion were present in 31.0 percent and 10.3 percent of nipple-sparing mastectomy specimens, respectively. Sentinel lymph node biopsy was performed in 84.9 percent of nipple-sparing mastectomies, and 17.8 percent were positive. The rate of positive frozen subareolar biopsy was 7.3 percent ( n = 82) and that of permanent subareolar pathology was 9.5 percent ( n = 126). The most frequently observed pathologic tumor stages were stage I (44.6 percent) and stage 0 (33.9 percent). The incidence of recurrent disease was 3.17 percent per mastectomy and 3.33 percent per patient. On univariate analysis, no demographic, operative, or tumor-specific variables were independent risk factors for locoregional recurrence., Conclusions: Overall recurrence rates are low in patients undergoing nipple-sparing mastectomy at a median follow-up of 10-years. Close surveillance should remain a goal for patients and their providers to promptly identify potential recurrence., Clinical Question/level of Evidence: Risk, III., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: Transmasculine individuals may not have undergone gender-affirming mastectomy and retain natal breast tissue. Our center offers simultaneous oncologic mastectomy with gender-affirming reconstruction to patients who are diagnosed with breast cancer. This study is the first reported series of concurrent gender-affirming and oncologic mastectomies., Methods: A retrospective chart review of all patients undergoing gender-affirming mastectomy at a single institution from February 2017 to October 2021 was performed. Patients were included who had breast cancer diagnoses or pathologic lesions preoperatively. Demographic factors, comorbidities, surgical details, and oncologic history were collected. Both plastic surgery and breast surgery were present for the gender-affirming oncologic mastectomies., Results: Five patients were identified who presented for gender-affirming mastectomy in the context of breast pathologies. Average patient age was 50.2 ± 14.8 years, and no patients used testosterone at any time. Two (40%) patients had a prior breast surgery that included a breast reduction in one patient and breast conserving lumpectomies in another. Sentinel lymph node biopsies were performed in all patients. Only one patient had a positive sentinel lymph node and was subsequently referred for postoperative radiation and chemotherapy. No oncologic recurrence has been detected with 20.6 and 10.0 months of mean and median follow-up., Conclusions: When performed in a multidisciplinary and collaborative setting with breast surgeons and plastic surgeons, oncologic mastectomy can be performed safely while concurrently offering patients an aesthetic gender-affirming reconstructive outcome., Competing Interests: Disclosure: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Summary: There remain significant gaps in the evidence-based care of patients undergoing gender-affirming mastectomy with regard to implications for breast cancer development and screening. The current clinical evidence does not demonstrate an increased risk of breast cancer secondary to testosterone therapy in transgender patients. Gender-affirmation mastectomy techniques vary significantly with regard to the amount of residual breast tissue left behind, which has unknown implications for the incidence of postoperative breast cancer and need for screening. Subcutaneous mastectomy should aim to remove all gross breast parenchyma, although this is limited in certain techniques. Tissue specimens should also be routinely sent for pathologic analysis. Several cases of incidental breast cancer after subcutaneous mastectomy have been described. There is little evidence on the need for or types of postoperative cancer screening. Chest awareness is an important concept for patients that have undergone subcutaneous mastectomies, as clinical examination remains the most common reported method of postmastectomy malignancy detection. In patients with greater known retained breast tissue, such as those with circumareolar or pedicled techniques, consideration may be given to alternative imaging modalities, although the efficacy and cost-utility of these techniques must still be proven. Preoperative patient counseling on the risk of breast cancer after gender-affirming mastectomy in addition to the unknown implications of residual breast tissue and long-term androgen exposure is critical. Patient awareness and education play an important role in shared decision-making, as further research is needed to define standards of medical and oncologic care in this population., (Copyright © 2021 by the American Society of Plastic Surgeons.)

3D visualization technologies have evolved to become a mainstay in the management of congenital heart disease (CHD) with a growing presence within multiple facets. Printed and virtual 3D models allow for a more comprehensive approach to educating trainees and care team members. Computational fluid dynamics can take 3D modeling to the next level, by predicting post-procedural outcomes and helping to determine surgical approach. 3D printing and extended reality are developing resources for pre-procedural planning and intra-procedural guidance with the potential to revolutionize decision-making and procedural success. Challenges still remain within existing technologies and their applications to the CHD field. Addressing these gaps, both by those within and outside of CHD, will transform education and patient care within our field.

Background: During kidney transplantation, the transplanted kidney undergoes ischemia reperfusion injury, with adenosine being a major mediator. This study aimed to assess whether aminophylline, an adenosine receptor antagonist, improves early graft function and reduces incidence of delayed graft function (DGF) and slow graft function (SGF)., Methods: Single center, double-blinded, placebo-controlled randomized clinical trial. Pediatric patients admitted for renal transplantation from donation after brain death donors were randomized into a treatment arm receiving aminophylline and a placebo arm receiving normal saline infusions. Primary outcome was estimated glomerular filtration rate (eGFR) at 5 days post-transplant. Secondary outcomes were rates of DGF/SGF and urinary neutrophil gelatinase-associated lipocalin (NGAL) levels., Results: Twenty-three patients were randomized to aminophylline and 27 to placebo. There was no difference in day 5 eGFR, rate of DGF/SGF, or urine NGAL/Creatinine level between aminophylline vs. placebo arm (eGFR 67.39 ± 38.9 ml/min/1.73m 2 vs. 80.48 ± 52.1 ml/min/1.73m 2 p = 0.32; DGF/SGF 5/23 (21.7%) vs. 3/27 (11.1%) p = 0.31; urine NGAL/creatinine 300.5 ng/mg IQR 105.5-1464.5 ng/mg vs. 425.4 ng/mg IQR 140.3-1126.2 ng/mg, p = 0.95; respectively). At 12 months, there was 100% patient survival and 98% graft survival. eGFR at 12 months was similar between the two arms., Conclusions: There was no benefit in peri-transplant aminophylline administration. Our results are limited by small sample size, since sample calculations were based on primary outcome of day 5 eGFR and low rate of DGF/SGF, which may have precluded us from demonstrating efficacy. Further clinical studies are necessary to determine any benefit of aminophylline in kidney transplant recipients, particularly from high-risk donors.

Purpose of Review: In the field of pediatric cardiology, a sub-specialty that relies on an understanding of complex three-dimensional structures, virtual reality technology may represent a new and exciting tool for both practitioners and patients. Here, the current medical and surgical applications of virtual reality are reviewed and the potential for future applications explored., Recent Findings: Multiple centers have begun to develop software designed to bring virtual reality technology to bear on congenital heart disease. These efforts have focused on surgical preparation, on education of medical providers, and on preparation of patients and their family members for cardiac interventions. Though relatively little statistical evidence for benefit has been generated to date, those studies currently available suggest that virtual reality may provide a significant benefit in all three of these aspects of medical care., Summary: The immersive nature of virtual reality meshes well with the learning styles of adult practitioners and promises to be a powerful tool for both pediatric cardiologists and the patients with whose care they are entrusted. Though additional studies are clearly needed, this technology promises to improve the field's ability to prepare providers and patients alike for challenge of treating congenital heart disease.

Background: No guidelines exist for inpatient postoperative transthoracic echocardiographic (TTE) surveillance in congenital heart disease. We prospectively evaluated indications for postoperative TTEs in patients with congenital heart disease to identify areas to improve upon (Phase 1) and then assessed the impact of a simple pilot intervention (Phase 2)., Methods: We included patients with RACHS-1 (Risk Adjustment for Congenital Heart Surgery) scores of 2 and 3 to keep the cohort homogenous. During Phase 1, we collected data prospectively to identify postoperative TTEs for which there were no new findings and no associated clinical management decisions ("potentially redundant" TTEs). During Phase 2, prior to placement of a TTE order, an "Echo Pause" was performed during rounds to prompt review of prior TTE results and indication for the current order. The number of "potentially redundant" TTEs during Phase 1 vs. Phase 2 was compared., Results: During Phase 1, 98 postoperative TTEs were performed on 51 patients. Potentially "redundant" TTEs were identified in two main areas: (a) TTEs ordered to evaluate pericardial effusion and (b) TTEs ordered with the indication of "postoperative," "follow-up," or "discharge" in the setting of a prior complete postoperative TTE and no apparent change in clinical status. During Phase 2, 101 TTEs were performed on 63 patients. The number of "potentially redundant" TTEs decreased from 14/98 (14%) to 5/101 (5%) (P = .026)., Conclusion: Our results suggest that the number of "potentially redundant" TTEs during inpatient postoperative surveillance of patients with congenital heart disease can be decreased by a simple intervention during rounds such as an "Echo Pause.", (© 2019 Wiley Periodicals, Inc.)

Objectives: Limited data exist for management of hyperuricemia in non-oncologic patients, particularly in paediatric cardiac patients. Hyperuricemia is a risk factor for acute kidney injury and may prompt treatment in critically ill patients. The primary objective was to determine if rasburicase use was associated with greater probability normalisation of serum uric acid compared to allopurinol. Secondary outcomes included percent reduction in uric acid, changes in serum creatinine, and cost of therapy., Design: A single-centre retrospective chart review., Setting: A 20-bed quaternary cardiovascular ICU in a university-based paediatric hospital in California., Patients: Patients admitted to cardiovascular ICU who received rasburicase or intravenous allopurinol between 2015 and 2016., Interventions: None., Measurements and Main Results: Data from a cohort of 14 patients receiving rasburicase were compared to 7 patients receiving IV allopurinol. Patients who were administered rasburicase for hyperuricemia were more likely to have a post-treatment uric acid level less than 8 mg/dl as compared to IV allopurinol (100 versus 43%; p = 0.0058). Patients who received rasburicase had a greater absolute reduction in post-treatment day 1 uric acid (-9 mg/dl versus -1.9 mg/dl; p = 0.002). There were no differences in post-treatment day 3 or day 7 serum creatinine or time to normalisation of serum creatinine. The cost of therapy normalised to a 20 kg patient was greater in the allopurinol group ($18,720 versus $1928; p = 0.001)., Conclusion: In a limited paediatric cardiac cohort, the use of rasburicase was associated with a greater reduction in uric acid levels and associated with a lower cost compared to IV allopurinol.

Background: Oncologic outcomes with nipple-sparing mastectomy continue to be established. The authors examine oncologic trends, outcomes, and risk factors, including tumor-to-nipple distance, in therapeutic nipple-sparing mastectomies., Methods: Demographics, outcomes, and overall trends for all nipple-sparing mastectomies performed for a therapeutic indication from 2006 to 2017 were analyzed. Oncologic outcomes were investigated with specific focus on recurrence and associated factors, including tumor-to-nipple distance., Results: A total of 496 therapeutic nipple-sparing mastectomies were performed, with an average follow-up time of 48.25 months. The most common tumor types were invasive carcinoma (52.4 percent) and ductal carcinoma in situ (50.4 percent). Sentinel lymph node sampling was performed in 79.8 percent of nipple-sparing mastectomies; 4.1 percent had positive frozen sentinel lymph node biopsy results, whereas 15.7 percent had positive nodal status on permanent pathologic examination. The most common pathologic cancer stage was stage IA (42.5 percent) followed by stage 0 (31.3 percent). The rate of local recurrence was 1.6 percent (n = 8), and the rate of regional recurrence was 0.6 percent (n = 3). In all, 171 nipple-sparing mastectomies had magnetic resonance imaging available with which to assess tumor-to-nipple distance. Tumor-to-nipple distance of 1 cm or less (25.0 percent versus 2.4 percent; p = 0.0031/p = 0.1129) and of 2 cm or less (8.7 percent versus 2.0 percent; p = 0.0218/p = 0.1345) trended to higher rates of locoregional recurrence. In univariate analysis, tumor-to-nipple distance of 1 cm or less was the only significant risk factor for recurrence (OR, 13.5833; p = 0.0385). No factors were significant in regression analysis., Conclusions: In early stage and in situ breast carcinoma, therapeutic nipple-sparing mastectomy appears oncologically safe, with a locoregional recurrence rate of 2.0 percent. Tumor-to-nipple distances of 1 cm or less and 2 cm or less trended to higher recurrence rates., Clinical Question/level of Evidence: Risk, III.

Introduction: Accurate assessment of estrogen receptor (ER) expression is crucial to ensure that patients with early breast cancer are accurately identified for appropriate treatment with endocrine therapy. Reverse transcriptase polymerase chain reaction (RT-PCR), compared with immunohistochemistry (IHC), may provide a more precise indication of ER status. Data were pooled and analyzed from two independent, but similarly designed, studies that examined ER status by IHC and the 21-gene Recurrence Score that employs RT-PCR-based methodology., Methods: Tumor tissue from patients with early stage breast cancer where ER status could be determined by both IHC and RT-PCR was included. ER status by IHC staining was defined as ER-negative (< 1%), ER-low+ (1-10%), or ER+ (> 10%). ER status by RT-PCR was defined as ER-negative (≤ 6.5) or ER+ (> 6.5). Recurrence Score results from the 21-gene assay were reported on a continuous scale from 0 to 100. A sub-analysis examined the association between ER expression (Allred score 2-7) and response to a 14-day pre-surgery pulse with an aromatase inhibitor. A separate sub-analysis examined the association between ER expression and human epidermal growth factor receptor 2 (HER2) expression., Results: Tumor specimens from 192 patients (aged 25-92 years) were included in the pooled analysis. Correlation between IHC- and RT-PCR-measured ER was strong for IHC-defined ER-negative and ER+ samples (r = 0.646 [95% CI 0.553-0.720]). There was 100% concordance for ER+ tumors; however, 56% of the ER-low+ tumors were negative by RT-PCR. Allred score correlated better with ER status measured by RT-PCR at pre-treatment (r = 0.83) than at post-treatment (r = 0.76). The majority (77%) of ER-negative and ER-low+ tumors were HER2-negative., Conclusions: RT-PCR provided a more accurate assessment of ER expression in patients with ER-low+ tumors, and data support dual testing for patients with ER-low+ status to ensure appropriate treatment planning as it pertains to endocrine therapy., Funding: Genomic Health, Inc.

The American Academy of Pediatrics classifies neonatal intensive care units (NICUs) from level I to IV based on the acuity of care each unit can provide. Birth in a higher level center is associated with lower morbidity and mortality in high-risk populations. Congenital heart disease accounts for 25-50% of infant mortality related to birth defects in the U.S., but recent data are lacking on where infants with critical congenital heart disease (CCHD) are born. We used a linked dataset from the Office of Statewide Health Planning and Development to access ICD-9 diagnosis codes for all infants born in California from 2008 to 2012. We compared infants with CCHD to the general population, identified where infants with CCHD were born based on NICU level of care, and predicted level IV birth among infants with CCHD using logistic regression techniques. From 2008 to 2012, 6325 infants with CCHD were born in California, with 23.7% of infants with CCHD born at a level IV NICU compared to 8.4% of the general population. Level IV birth for infants with CCHD was associated with lower gestational age, higher maternal age and education, the presence of other congenital anomalies, and the diagnosis of a single ventricle lesion. More infants with CCHD are born in a level IV NICU compared to the general population. Future studies are needed to determine if birth in a lower level of care center impacts outcomes for infants with CCHD.

The care of children with hypoplastic left heart syndrome is constantly evolving. Prenatal diagnosis of hypoplastic left heart syndrome will aid in counselling of parents, and selected fetuses may be candidates for in utero intervention. Following birth, palliation can be undertaken through staged operations: Norwood (or hybrid) in the 1st week of life, superior cavopulmonary connection at 4-6 months of life, and finally total cavopulmonary connection (Fontan) at 2-4 years of age. Children with hypoplastic left heart syndrome are at risk of circulatory failure their entire life, and selected patients may undergo heart transplantation. In this review article, we summarise recent advances in the critical care management of patients with hypoplastic left heart syndrome as were discussed in a focused session at the 12th International Conference of the Paediatric Cardiac Intensive Care Society held on 9 December, 2016, in Miami Beach, Florida.

Background: Fluid overload (FO) is common after neonatal congenital heart surgery and may contribute to mortality and morbidity. It is unclear if the effects of FO are independent of acute kidney injury (AKI)., Methods: This was a retrospective cohort study which examined neonates (age < 30 days) who underwent cardiopulmonary bypass in a university-affiliated children's hospital between 20 October 2010 and 31 December 2012. Demographic information, risk adjustment for congenital heart surgery score, surgery type, cardiopulmonary bypass time, cross-clamp time, and vasoactive inotrope score were recorded. FO [(fluid in-out)/pre-operative weight] and AKI defined by Kidney Disease Improving Global Outcomes serum creatinine criteria were calculated. Outcomes were all-cause, in-hospital mortality and median postoperative hospital and intensive care unit lengths of stay., Results: Overall, 167 neonates underwent cardiac surgery using cardiopulmonary bypass in the study period, of whom 117 met the inclusion criteria. Of the 117 neonates included in the study, 76 (65%) patients developed significant FO (>10%), and 25 (21%) developed AKI ≥ Stage 2. When analyzed as FO cohorts (< 10%,10-20%, > 20% FO), patients with greater FO were more likely to have AKI (9.8 vs. 18.2 vs. 52.4%, respectively, with AKI ≥ stage 2; p = 0.013) and a higher vasoactive-inotrope score, and be premature. In the multivariable regression analyses of patients without AKI, FO was independently associated with hospital and intensive care unit lengths of stay [0.322 extra days (p = 0.029) and 0.468 extra days (p < 0.001), respectively, per 1% FO increase). In all patients, FO was also associated with mortality [odds ratio 1.058 (5.8% greater odds of mortality per 1% FO increase); 95% confidence interval 1.008,1.125;p = 0.032]., Conclusions: Fluid overload is an important independent contributor to outcomes in neonates following congenital heart surgery. Careful fluid management after cardiac surgery in neonates with and without AKI is warranted.

Perinatal mortality remains high among fetuses diagnosed with Ebstein's anomaly of the tricuspid valve. The subgroup of patients with pulmonary valve regurgitation is at particularly high risk. In the setting of pulmonary valve regurgitation, early constriction of the ductus arteriosus may be a novel perinatal management strategy to reduce systemic steal resulting from circular shunt physiology. We report the use of chronic antepartum maternal oxygen therapy for constriction of the fetal ductus arteriosus and modulation of fetal pulmonary vascular resistance in a late presentation of Ebstein's anomaly with severe tricuspid valve regurgitation, reversal of flow in the ductus arteriosus, and continuous pulmonary valve regurgitation., Competing Interests: There are no conflicts of interest.

Background: Acute kidney injury after cardiac surgery is a frequent and serious complication among children with congenital heart disease (CHD) and adults with acquired heart disease; however, the significance of kidney injury in adults after congenital heart surgery is unknown. The primary objective of this study was to determine the incidence of acute kidney injury after surgery for adult CHD. Secondary objectives included determination of risk factors and associations with clinical outcomes., Methods: This single-centre, retrospective cohort study was performed in a quaternary cardiovascular ICU in a paediatric hospital including all consecutive patients ⩾18 years between 2010 and 2013., Results: Data from 118 patients with a median age of 29 years undergoing cardiac surgery were analysed. Using Kidney Disease: Improving Global Outcome creatinine criteria, 36% of patients developed kidney injury, with 5% being moderate to severe (stage 2/3). Among higher-complexity surgeries, incidence was 59%. Age ⩾35 years, preoperative left ventricular dysfunction, preoperative arrhythmia, longer bypass time, higher Risk Adjustment for Congenital Heart Surgery-1 category, and perioperative vancomycin use were significant risk factors for kidney injury development. In multivariable analysis, age ⩾35 years and vancomycin use were significant predictors. Those with kidney injury were more likely to have prolonged duration of mechanical ventilation and cardiovascular ICU stay in the univariable regression analysis., Conclusions: We demonstrated that acute kidney injury is a frequent complication in adults after surgery for CHD and is associated with poor outcomes. Risk factors for development were identified but largely not modifiable. Further investigation within this cohort is necessary to better understand the problem of kidney injury.

Background: Pediatric sepsis has a high mortality rate in limited resource settings. Sepsis protocols have been shown to be a cost-effective strategy to improve morbidity and mortality in a variety of populations and settings. At Dhaka Hospital in Bangladesh, mortality from pediatric sepsis in high-risk children previously approached 60%, which prompted the implementation of an evidenced-based protocol in 2010. The clinical effectiveness of this protocol had not been measured. We hypothesized that implementation of a pediatric sepsis protocol improved clinical outcomes, including reducing mortality and length of hospital stay., Materials and Methods: This was a retrospective cohort study of children 1-59 months old with a diagnosis of sepsis, severe sepsis or septic shock admitted to Dhaka Hospital from 10/25/2009-10/25/2011. The primary outcome was inpatient mortality pre- and post-protocol implementation. Secondary outcomes included fluid overload, heart failure, respiratory insufficiency, length of hospital stay, and protocol compliance, as measured by antibiotic and fluid bolus administration within 60 minutes of hospital presentation., Results: 404 patients were identified by a key-word search of the electronic medical record; 328 patients with a primary diagnosis of sepsis, severe sepsis, or septic shock were included (143 pre- and185 post-protocol) in the analysis. Pre- and post-protocol mortality were similar and not statistically significant (32.17% vs. 34.59%, p = 0.72). The adjusted odds ratio (AOR) for post-protocol mortality was 1.55 (95% CI, 0.88-2.71). The odds for developing fluid overload were significantly higher post-protocol (AOR 3.45, 95% CI, 2.04-5.85), as were the odds of developing heart failure (AOR 4.52, 95% CI, 1.43-14.29) and having a longer median length of stay (AOR 1.81, 95% CI 1.10-2.96). There was no statistically significant difference in respiratory insufficiency (pre- 65.7% vs. post- 70.3%, p = 0.4) or antibiotic administration between the cohorts (pre- 16.08% vs. post- 12.43%, p = 0.42)., Conclusions: Implementation of a pediatric sepsis protocol did not improve all-cause mortality or length of stay and may have been associated with increased fluid overload and heart failure during the study period in a large, non-governmental hospital in Bangladesh. Similar rates of early antibiotic administration may indicate poor protocol compliance. Though evidenced-based protocols are a potential cost-effective strategy to improve outcomes, future studies should focus on optimal implementation of context-relevant sepsis protocols in limited resource settings.

The effect of veno-arterial extracorporeal membrane oxygenation (VA ECMO) on wall stress in patients with cardiomyopathy, myocarditis, or other cardiac conditions is unknown. We set out to determine the circumferential and meridional wall stress (WS) in patients with systemic left ventricles before and during VA ECMO. We established a cohort of patients with impaired myocardial function who underwent VA ECMO therapy from January 2000 to November 2013. Demographic and clinical data were collected and inotropic score calculated. Measurements were taken on echocardiograms prior to the initiation of VA ECMO and while on full-flow VA ECMO, in order to derive wall stress (circumferential and meridional), VCFc, ejection fraction, and fractional shortening. A post hoc sub-analysis was conducted, separating those with pulmonary hypertension (PH) and those with impaired systemic output. Thirty-three patients met inclusion criteria. The patients' median age was 0.06 years (range 0-18.7). Eleven (33%) patients constituted the organ failure group (Gr2), while the remaining 22 (66%) patients survived to discharge (Gr1). WS and all other echocardiographic measures were not different when comparing patients before and during VA ECMO. Ejection and shortening fraction, WS, and VCFc were not statistically different comparing the survival and organ failure groups. The patients' position on the VCFc-WS curve did not change after the initiation of VA ECMO. Those with PH had decreased WS as well as increased EF after ECMO initiation, while those with impaired systemic output showed no difference in those parameters with initiation of ECMO. The external workload on the myocardium as indicated by WS is unchanged by the institution of VA ECMO support. Furthermore, echocardiographic measures of cardiac function do not reflect the changes in ventricular performance inherent to VA ECMO support. These findings are informative for the interpretation of echocardiograms in the setting of VA ECMO. ECMO may improve ventricular mechanics in those with PH as the primary diagnosis.

We previously demonstrated that a pediatric cardiology boot camp can improve knowledge acquisition and decrease anxiety for trainees. We sought to determine if boot camp participants entered fellowship with a knowledge advantage over fellows who did not attend and if there was moderate-term retention of that knowledge. A 2-day training program was provided for incoming pediatric cardiology fellows from eight fellowship programs in April 2016. Hands-on, immersive experiences and simulations were provided in all major areas of pediatric cardiology. Knowledge-based examinations were completed by each participant prior to boot camp (PRE), immediately post-training (POST), and prior to the start of fellowship in June 2016 (F/U). A control group of fellows who did not attend boot camp also completed an examination prior to fellowship (CTRL). Comparisons of scores were made for individual participants and between participants and controls. A total of 16 participants and 16 control subjects were included. Baseline exam scores were similar between participants and controls (PRE 47 ± 11% vs. CTRL 52 ± 10%; p = 0.22). Participants' knowledge improved with boot camp training (PRE 47 ± 11% vs. POST 70 ± 8%; p < 0.001) and there was excellent moderate-term retention of the information taught at boot camp (PRE 47 ± 11% vs. F/U 71 ± 8%; p < 0.001). Testing done at the beginning of fellowship demonstrated significantly better scores in participants versus controls (F/U 71 ± 8% vs. CTRL 52 ± 10%; p < 0.001). Boot camp participants demonstrated a significant improvement in basic cardiology knowledge after the training program and had excellent moderate-term retention of that knowledge. Participants began fellowship with a larger fund of knowledge than those fellows who did not attend.

Objectives: To describe the prevalence and risk factors for acute kidney injury in patients undergoing the extracardiac Fontan operation with and without cardiopulmonary bypass, and to determine whether acute kidney injury is associated with duration of mechanical ventilation, cardiovascular ICU and hospital postoperative length of stay, and early mortality., Design: Single-center retrospective cohort study., Setting: Pediatric cardiovascular ICU, university-affiliated children's hospital., Patients: Patients with a preoperative creatinine before undergoing first-time extracardiac Fontan between January 1, 2004, and April 30, 2012., Interventions: None., Measurements and Main Results: Acute kidney injury occurred in 55 of 138 patients (39.9%), including 41 (29.7%) with stage 1, six (4.4%) with stage 2, and eight (5.8%) with stage 3 acute kidney injury. Cardiopulmonary bypass was strongly associated with a higher risk of any acute kidney injury (adjusted odds ratio, 4.8 [95% CI, 1.4-16.0]; p = 0.01) but not stage 2/3 acute kidney injury. Lower renal perfusion pressure on the day of surgery (postoperative day, 0) was associated with a higher risk of stage 2/3 acute kidney injury (adjusted odds ratio, 1.2 [95% CI, 1.0-1.5]; p = 0.03). Higher vasoactive-inotropic score on postoperative day 0 was associated with a higher risk for stage 2/3 acute kidney injury (adjusted odds ratio, 1.9 [95% CI, 1.0-3.4]; p = 0.04). Stage 2/3 acute kidney injury was associated with longer cardiovascular ICU length of stay (mean, 7.3 greater d [95% CI, 3.4-11.3]; p < 0.001) and hospital postoperative length of stay (mean, 6.4 greater d [95% CI, 0.06-12.5]; p = 0.04)., Conclusions: Postoperative acute kidney injury in patients undergoing the extracardiac Fontan operation is common and is associated with lower postoperative renal perfusion pressure and higher vasoactive-inotropic score. Cardiopulmonary bypass was strongly associated with any acute kidney injury, although not stage 2/3 acute kidney injury. Stage 2/3 acute kidney injury is a compelling risk factor for longer cardiovascular ICU and hospital postoperative length of stay. Increased attention to and management of renal perfusion pressure may reduce postoperative acute kidney injury and improve outcomes.

Objectives: To review current institutional practice and describe factors contributing to variation in inpatient postoperative imaging surveillance after congenital heart surgery., Study Design: We reviewed records of all children who underwent congenital heart surgery from June to December 2014. Number and primary indications for postoperative transthoracic echocardiograms (TTEs), providers involved, cardiovascular intensive care unit (CVICU) and total hospital length of stay, and Risk-Adjustment for Congenital Heart Surgery-1 scores were recorded., Results: A total of 253 children (age at surgery: 8 months [2 days-19 years]) received 556 postoperative TTEs (median 1 TTE/patient [1-14]), and 23% had ≥3 TTEs. Fifteen of 556 TTEs (2.7%) revealed a new abnormal finding. The majority of TTEs (59%) were performed in the CVICU (1.5 ± 1.1 TTEs/week/patient), with evaluation of function as the most common indication (44%). Attending physician practice >10 years was not associated with fewer TTEs (P = .12). Patients with ≥3 TTEs had higher Risk-Adjustment for Congenital Heart Surgery-1 scores (P = .001), longer CVICU lengths of stay (22 vs 3 days; P < .0001), longer overall hospitalizations (28 vs 7 days; P < .0001), and a higher incidence of mechanical circulatory support (10% vs 0%; P < .0001) than those with <3 TTEs. Eight patients with ≥3 TTEs did not survive, compared with 3 with <3 TTEs (P = .0004)., Conclusions: There was wide intra-institutional variation in echocardiographic use among similar complexity surgeries. Frequency of postoperative echocardiographic surveillance was associated with degree of surgical complexity and severity of postoperative clinical condition. Few studies revealed new abnormal findings. These results may help establish evidence-based guidelines for inpatient echocardiographic surveillance after congenital heart surgery., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Children undergoing cardiac surgery requiring cardiopulmonary bypass (CPB) frequently develop acute kidney injury due to renal ischemia. Theophylline, which improves renal perfusion via adenosine receptor inhibition, is a potential targeted therapy. However, children undergoing cardiac surgery and CPB commonly have alterations in drug pharmacokinetics. To help understand optimal aminophylline (salt formulation of theophylline) dosing strategies in this population, a population-based pharmacokinetic model was developed using nonlinear mixed-effects modeling (NONMEM) from 71 children (median age 5 months; 90% range 1 week to 10 years) who underwent cardiac surgery requiring CPB and received aminophylline as part of a previous randomized controlled trial. A 1-compartment model with linear elimination adequately described the pharmacokinetics of theophylline. Weight scaled via allometry was a significant predictor of clearance and volume. In addition, allometric scaled clearance increased with age implemented as a power maturation function. Compared to prior reports in noncardiac children, theophylline clearance was markedly reduced across age. In the final population pharmacokinetic model, optimized empiric dosing regimens were developed via Monte Carlo simulations. Doses 50% to 75% lower than those recommended in noncardiac children were needed to achieve target serum concentrations of 5 to 10 mg/L., (© 2016, The American College of Clinical Pharmacology.)

Background: Acute kidney injury (AKI) is common in children following surgery for congenital heart disease and has been associated with poor long-term kidney outcomes. Children undergoing heart transplantation may be at increased risk for the development of both AKI and chronic kidney disease (CKD). This study examines AKI rates in children, adolescents, and young adults after heart transplantation and analyzes the relationship between AKI and CKD in this population., Study Design: Retrospective cohort study., Setting & Participants: 88 young patients who underwent heart transplantation at Lucile Packard Children's Hospital, Stanford, CA, September 1, 2007, to November 30, 2013., Predictor: The primary independent variable was AKI within the first 7 postoperative days, ascertained according to the KDIGO (Kidney Disease: Improving Global Outcomes) creatinine criteria (increase in serum creatinine ≥ 1.5 times baseline within 7 days)., Outcomes: Recovery from AKI at 3 months, ascertained as serum creatinine level < 1.5 times baseline; and development of CKD at 6 and 12 months, ascertained as estimated glomerular filtration rate < 60mL/min/1.73m(2) for more than 3 months., Results: 63 (72%) patients developed AKI; 57% had moderate (stage 2 or severe stage 3) disease. Recovery occurred in 39 of 63 (62%), 50% for stage 2 or 3 versus 78% for stage 1 (P=0.04). At 6 and 12 months, 3 of 82 (4%) and 4 of 76 (5%) developed CKD, respectively. At both time points, CKD was more common in those without recovery (3/22 [14%] vs 0/38 (0%); P=0.04, and 3/17 (18%) vs (0/34) 0%; P=0.03, respectively)., Limitations: Retrospective design, small sample size, and single-center nature of the study., Conclusions: AKI is common after heart transplantation in children, adolescents, and young adults. Nonrecovery from AKI is more common in patients with more severe AKI and is associated with the development of CKD during the first year., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

The transition from residency to subspecialty fellowship in a procedurally driven field such as pediatric cardiology is challenging for trainees. We describe and assess the educational value of a pediatric cardiology "boot camp" educational tool designed to help prepare trainees for cardiology fellowship. A two-day intensive training program was provided for pediatric cardiology fellows in July 2015 at a large fellowship training program. Hands-on experiences and simulations were provided in: anatomy, auscultation, echocardiography, catheterization, cardiovascular intensive care (CVICU), electrophysiology (EP), heart failure, and cardiac surgery. Knowledge-based exams as well as surveys were completed by each participant pre-training and post-training. Pre- and post-exam results were compared via paired t tests, and survey results were compared via Wilcoxon rank sum. A total of eight participants were included. After boot camp, there was a significant improvement between pre- and post-exam scores (PRE 54 ± 9 % vs. POST 85 ± 8 %; p ≤ 0.001). On pre-training survey, the most common concerns about starting fellowship included: CVICU emergencies, technical aspects of the catheterization/EP labs, using temporary and permanent pacemakers/implantable cardiac defibrillators (ICDs), and ECG interpretation. Comparing pre- and post-surveys, there was a statistically significant improvement in the participants comfort level in 33 of 36 (92 %) areas of assessment. All participants (8/8, 100 %) strongly agreed that the boot camp was a valuable learning experience and helped to alleviate anxieties about the start of fellowship. A pediatric cardiology boot camp experience at the start of cardiology fellowship can provide a strong foundation and serve as an educational springboard for pediatric cardiology fellows.

Background: Although ventricular assist devices (VADs) restore hemodynamics in those with heart failure, reversibility of end-organ dysfunction with VAD support is not well characterized. Renal function often improves in adults after VAD placement, but this has not been comprehensively explored in children., Methods: Sixty-three children on VAD support were studied. Acute kidney injury (AKI) was defined by Kidney Disease: Improving Global Outcomes criteria. Estimated glomerular filtration rate (eGFR) was determined by the Schwartz method. Generalized linear mixed-effects models compared the pre-VAD and post-VAD eGFR for the cohort and sub-groups with and without pre-VAD renal dysfunction (pre-VAD eGFR < 90 ml/min/1.73 m(2))., Results: The pre-VAD eGFR across the cohort was 84.0 ml/min/1.73 m(2) (interquartile range [IQR] 62.3-122.7), and 55.6% (34 of 63) had pre-VAD renal dysfunction. AKI affected 60.3% (38 of 63), with similar rates in those with and without pre-existing renal dysfunction. Within the cohort, the nadir eGFR occurred 1 day post-operatively (62.9 ml/min/1.73 m(2); IQR, 51.2-88.9 ml/min/1.73 m(2); p < 0.001). By Day 5, however, the eGFR exceeded the baseline (99.0 ml/min/1.73 m(2); IQR, 59.3-146.7 ml/min/1.73 m(2); p = 0.03) and remained significantly higher through the first post-operative week. After adjusting for age, gender, and AKI, the eGFR continued to increase throughout the entire 180-day study period (β = 0.0025; 95% confidence interval, 0.0015-0.0036; p < 0.001). Patients with pre-VAD renal dysfunction experienced the greatest improvement in the eGFR (β = 0.0051 vs β = 0.0013, p < 0.001)., Conclusions: Renal dysfunction is prevalent in children with heart failure undergoing VAD placement. Although peri-operative AKI is common, renal function improves substantially in the first post-operative week and for months thereafter. This is particularly pronounced in those with pre-VAD renal impairment, suggesting that VADs may facilitate recovery and maintenance of kidney function in children with advanced heart failure., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objective: In this Consensus Statement, we review the etiology and pathophysiology of fluid disturbances in critically ill children with cardiac disease. Clinical tools used to recognize pathologic fluid states are summarized, as are the mechanisms of action of many drugs aimed at optimal fluid management., Data Sources: The expertise of the authors and a review of the medical literature were used as data sources., Data Synthesis: The authors synthesized the data in the literature in order to present clinical tools used to recognize pathologic fluid states. For each drug, the physiologic rationale, mechanism of action, and pharmacokinetics are synthesized, and the evidence in the literature to support the therapy is discussed., Conclusions: Fluid management is challenging in critically ill pediatric cardiac patients. A myriad of causes may be contributory, including intrinsic myocardial dysfunction with its associated neuroendocrine response, renal dysfunction with oliguria, and systemic inflammation with resulting endothelial dysfunction. The development of fluid overload has been associated with adverse outcomes, including acute kidney injury, prolonged mechanical ventilation, increased vasoactive support, prolonged hospital length of stay, and mortality. An in-depth understanding of the many factors that influence volume status is necessary to guide optimal management.

The premature neonate with congenital heart disease (CHD) represents a challenging population for clinicians and researchers. The interaction between prematurity and CHD is poorly understood; epidemiologic study suggests that premature newborns are more likely to have CHD and that fetuses with CHD are more likely to be born premature. Understanding the key physiologic features of this special patient population is paramount. Clinicians have debated optimal timing for referral for cardiac surgery, and management in the postoperative period has rapidly advanced. This article summarizes the key concepts and literature in the care of the premature neonate with CHD., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Permanent paraffin subareolar biopsy during nipple-sparing mastectomy (NSM) tests for occult cancer at the nipple-areolar complex. Intraoperative subareolar frozen section can provide earlier detection intraoperatively. Cost analysis for intraoperative subareolar frozen section has never been performed., Methods: NSM cases from 2006-2013 were reviewed. Patient records including financial charges were analyzed., Results: Of 480 subareolar biopsies for NSM from 2006-2013, 21 were abnormal (4.4 %). A total of 307 of the subareolar biopsies included intraoperative frozen section. Of the 307, 12 (3.9 %) were abnormal with 7 of 12 detected on intraoperative frozen section. The median baseline charge for an intraoperative subareolar frozen section was $309 for an estimated total cost of $94,863 in 307 breasts. The median baseline charge for interval operative resection of a nipple-areolar complex following an abnormal subareolar pathology result was $11,021. Intraoperative subareolar biopsy avoided an estimated six return trips to the operating room for savings of $66,126. At our institution, routine use of intraoperative frozen section resulted in an additional $28,737 in healthcare charges or $95 per breast., Conclusions: We present the first cost analysis to evaluate intraoperative subareolar frozen section in NSM. This practice obviated an estimated six return trips to the operating room. With our institutional frequency of abnormal subareolar pathology, intraoperative frozen sections resulted in a marginal increased charge per mastectomy.

Objectives: Recent data have suggested an association between the use of dexmedetomidine and a decreased incidence of acute kidney injury in adult patients after cardiopulmonary bypass. However, no study has focused on this association among pediatric populations where the incidence of acute kidney injury is particularly high and of critical significance. The primary objective of this study was to assess the relationship between the use of postoperative dexmedetomidine and the incidence of acute kidney injury in pediatric patients undergoing cardiopulmonary bypass. The secondary objective was to determine whether there was an association between dexmedetomidine use and duration of mechanical ventilation or cardiovascular ICU stay., Design: Single-center retrospective matched cohort study., Setting: A 20-bed quaternary cardiovascular ICU in a university-based pediatric hospital in California., Patients: Children less than 18 years old admitted after cardiac surgery with cardiopulmonary bypass between January 1, 2012, and May 31, 2014., Interventions: None., Measurements and Main Results: Data from a cohort of 102 patients receiving dexmedetomidine during the first postoperative day after cardiac surgery were compared to an age- and procedure-matched cohort not receiving dexmedetomidine. Cohorts had similar baseline and demographic characteristics. Patients receiving dexmedetomidine were less likely to develop acute kidney injury (24% vs 36%; odds ratio, 0.54; 95% CI, 0.29-0.99; p = 0.046). After adjusting for age, bypass time, nephrotoxin use, and vasoactive inotropic score, the use of dexmedetomidine was associated with a lower incidence of acute kidney injury with adjusted odds ratio of 0.43 (95% CI, 0.27-0.98; p = 0.048). There was no difference between the cohorts with respect to the duration of mechanical duration (1 d each; p = 0.98) or cardiovascular ICU stays (5 vs 6 d; p = 0.91)., Conclusions: The use of a dexmedetomidine infusion in pediatric patients after congenital heart surgery was associated with a decreased incidence of acute kidney injury; however, it was not associated with changes in clinical outcomes. Further prospective study is necessary to validate these findings.

Objectives: Acute kidney injury occurs commonly in children following congenital cardiac surgery with cardiopulmonary bypass and has been associated with increased morbidity and mortality. Aminophylline, a methylxanthine nonselective adenosine receptor antagonist, has been effective in the management of acute kidney injury in certain populations. This study sought to determine whether postoperative administration of aminophylline attenuates acute kidney injury in children undergoing congenital cardiac surgery with cardiopulmonary bypass., Design: Single-center, double-blinded, placebo-controlled, randomized clinical trial., Setting: Tertiary center, pediatric cardiovascular ICU., Patients: A total of 144 children after congenital heart surgery with cardiopulmonary bypass., Interventions: Seventy-two patients were randomized to receive aminophylline and 72 patients received placebo. Study drug was administered every 6 hours for 72 hours., Measurements and Main Results: The primary outcome variable was the development of any acute kidney injury, defined by the serum creatinine criteria of the Kidney Diseases: Improving Global Outcomes. Secondary outcomes included the development of severe acute kidney injury, time between cardiovascular ICU admission and first successful extubation, percent fluid overload, total fluid balance, urine output, bioelectrical impedance, and serum neutrophil gelatinase-associated lipocalin. The unadjusted rate and severity of acute kidney injury were not different between groups; 43 of 72 (60%) of the treatment group and 36 of 72 (50%) of the placebo group developed acute kidney injury (p = 0.32). Stage 2/3 acute kidney injury occurred in 23 of 72 (32%) of the treatment group and 15 of 72 (21%) of the placebo group (p = 0.18). Secondary outcome measures also demonstrated no significant difference between treatment and placebo groups. Aminophylline administration was safe; no deaths occurred in either group, and rates of adverse events were similar (14% in the treatment group vs 18% in the placebo group; p = 0.30)., Conclusions: In this placebo-controlled randomized clinical trial, we found no effect of aminophylline to prevent acute kidney injury in children recovering from cardiac surgery performed with cardiopulmonary bypass. Future study of preoperative aminophylline administration to prevent acute kidney injury may be warranted.

Introduction: Long-term oncologic outcomes in nipple-sparing mastectomy (NSM) continue to be defined. Rates of locoregional recurrence for skin-sparing mastectomy (SSM) and NSM in the literature range from 0% to 14.3%. We investigated the outcomes of NSM at our institution., Methods: Patients undergoing NSM at our institution from 2006 to 2014 were identified and outcomes were analyzed., Results: From 2006 to 2014, 319 patients (555 breasts) underwent NSM. One-hundered and fourty-one patients (237 breasts) had long-term follow-up available. Average patient age and BMI were 47.78 and 24.63. Eighty-four percent of patients underwent mastectomy primarily for a therapeutic indication. Average tumor size was 1.50 cm with the most common histologic type being invasive ductal carcinoma (62.7%) followed by DCIS (23.7%). Average patient follow-up was 30.73 months. There was one (0.8%) incidence of ipsilateral chest-wall recurrence. There were 0.37 complications per patient., Conclusions: We examined our institutional outcomes with NSM and found a locoregional recurrence rate of 0.8% with no nipple-areolar complex recurrence. This rate is lower than published rates for both NSM and SSM., (© 2015 Wiley Periodicals, Inc.)

Use of nipple-sparing mastectomy (NSM) for risk-reduction and therapeutic breast cancer resection is growing. The role for intraoperative frozen section of the nipple-areolar complex remains controversial. Records of patients undergoing NSM at our institution from 2006 to 2013 were reviewed. Records from 501 nipple-sparing mastectomies were reviewed (216 therapeutic, 285 prophylactic). Of the 480 breasts with sub-areolar biopsies, 307 had intraoperative frozen sections and 173 were evaluated with permanent paraffin section only. Among the 307 intraoperative frozen sections, 12 biopsies were positive on permanent paraffin section (3.9% or 12/307). Of the 12 positive permanent biopsies, five were false negative and the remaining seven concordant intraoperatively. Sensitivity and specificity of sub-areolar frozen section were 0.58 and 1, respectively. Positive sub-areolar biopsies consisted primarily of ductal carcinoma in situ (62% or 13/21). The nipples or nipple-areolar complex were resected in a separate procedure following mastectomy (10/21), intraoperatively following frozen section results (7/21) or during second-stage breast reconstruction (3/21; 1 additional scheduled). Only 30% (6/20) of resected specimens had abnormal residual pathology. Intraoperative frozen section is highly specific and moderately sensitive for the detection of positive sub-areolar biopsies in NSM. Its use can help guide intraoperative reconstructive planning. The presence of positive sub-areolar biopsies in both contralateral and high-risk prophylactic mastectomy specimens emphasizes the need to perform sub-areolar biopsies in all nipple-sparing mastectomies., (© 2015 Wiley Periodicals, Inc.)

The increase in pediatric cardiac surgical procedures and establishment of the practice of pediatric cardiac intensive care has created the need for physicians with advanced and specialized knowledge and training. Current training pathways to become a pediatric cardiac intensivist have a great deal of variability and have unique strengths and weaknesses with influences from critical care, cardiology, neonatology, anesthesiology, and cardiac surgery. Such variability has created much confusion among trainees looking to pursue a career in our specialized field. This is a report with perspectives from the most common advanced fellowship training pathways taken to become a pediatric cardiac intensivist as well as various related topics including scholarship, qualifications, and credentialing., (© The Author(s) 2015.)

Since the inception of the Pediatric Cardiac Intensive Care Society (PCICS) in 2003, remarkable advances in the care of children with critical cardiac disease have been developed. Specialized surgical approaches, anesthesiology practices, and intensive care management have all contributed to improved outcomes. However, significant morbidity often results from immunologic or infectious disease in the perioperative period or during a medical intensive care unit admission. The immunologic or infectious illness may lead to fever, which requires the attention and resources of the cardiac intensivist. Frequently, cardiopulmonary bypass leads to an inflammatory state that may present hemodynamic challenges or complicate postoperative care. However, inflammation unchecked by a compensatory anti-inflammatory response may also contribute to the development of capillary leak and lead to a complicated intensive care unit course. Any patient admitted to the intensive care unit is at risk for a hospital acquired infection, and no patients are at greater risk than the child treated with mechanical circulatory support. In summary, the prevention, diagnosis, and management of immunologic and infectious diseases in the pediatric cardiac intensive care unit is of paramount importance for the clinician. This review from the tenth PCICS International Conference will summarize the current knowledge in this important aspect of our field., (© The Author(s) 2015.)

Isolation of the right subclavian artery (RSCA) is rare, and this finding in association with d-transposition of the great arteries (d-TGA) is extremely unusual. We present a case of an isolated RSCA in a newborn with d-TGA in whom the clinical presentation was diagnostic. We discuss the imaging modalities used to confirm the diagnosis, the embryological basis of the finding, and the surgical repair.

Background: Chronic right ventricular (RV) pacing has been associated with decreased exercise capacity and left ventricular (LV) function in adults with congenital complete atrioventricular block (CCAVB), but not in children., Objective: The purpose of this study was to evaluate the exercise capacity and LV function in pediatric patients with CCAVB receiving chronic RV pacing., Methods: We prospectively evaluated pediatric patients with isolated CCAVB receiving atrial synchronous RV pacing for at least 5 years. Supine bicycle ergometry was performed, and LV ejection fraction (EF) was evaluated by echocardiography., Results: Ten CCAVB subjects and 31 controls were matched for age, gender, and body surface area. CCAVB subjects had normal resting EF (63.1% ± 4.0%) and had been paced for 7.9 ± 1.4 years. Exercise testing demonstrated reduced functional capacity in CCAVB patients compared to controls with a lower VO₂peak (26.0 ± 6.6 mL/kg/min vs 39.9 ± 7.0 mL/kg/min, P <.001), anaerobic threshold (15.6 ± 3.9 mL/kg/min vs 18.8 ± 2.7 mL/kg/min, P = .007), and oxygen uptake efficiency slope (1210 ± 406 vs 1841 ± 452, P <.001). Maximum heart rate (165 ± 8 bpm vs 185 ± 9 bpm, P <.001) and systolic blood pressure (159 ± 17 mm Hg vs 185 ± 12 mm Hg, P <.019) also were reduced in CCAVB patients despite maximal effort (respiratory exchange ratio 1.2 ± 0.1). EF was augmented with exercise in controls but not in CCAVB patients (13.2% ± 9.3% vs 0.2% ± 4.8% increase, P <.001)., Conclusion: Clinically asymptomatic children with chronic RV pacing due to CCAVB have significant reductions in functional capacity accompanied by chronotropic incompetence and inability to augment EF with exercise., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Estrogen inhibition is effective in preventing breast cancer in only up to 50% of women with precancerous lesions and many experience side effects that are poorly tolerated. As insulin-like growth factor I (IGF-I) underlies both estrogen and progesterone actions and has other direct effects on mammary development and carcinogenesis, we hypothesized that IGF-I inhibition might provide a novel approach for breast cancer chemoprevention., Methods: In total, 13 women with core breast biopsies diagnostic of atypical hyperplasia (AH) were treated for 10 days with pasireotide, a somatostatin analog which uniquely inhibits IGF-I action in the mammary gland. They then had excision biopsies. 12 patients also had proliferative lesions and one a ductal carcinoma in situ (DCIS). Primary outcomes were changes in cell proliferation and apoptosis after treatment. Expression of estrogen receptor (ER), progesterone receptor (PR), and phosphorylated Insulin-like growth factor I receptor (IGF-1R), protein kinase B (AKT) and extracellular signal-regulated kinases 1/2 (ERK1/2) were also assessed. Core and excision biopsies from 14 untreated patients served as non-blinded controls. Hyperglycemia and other side effects were carefully monitored., Results: Pasireotide decreased proliferation and increased apoptosis in all AH (from 3.6 ± 2.6% to 1.3 ± 1.2% and from 0.3 ± 0.2% to 1.5 ± 1.6%, respectively) and proliferative lesions (from 3.8 ± 2.5% to 1.8 ± 1.8% and from 0.3 ± 0.2% to 1.3 ± 0.6%, respectively). The DCIS responded similarly. ER and PR were not affected by pasireotide, while IGF-1R, ERK1/2 and AKT phosphorylation decreased significantly. In contrast, tissue from untreated controls showed no change in cell proliferation or phosphorylation of IGF-1R, AKT or ERK 1/2. Mild to moderate hyperglycemia associated with reduced insulin levels was found. Glucose fell into the normal range after discontinuing treatment. Pasireotide was well tolerated and did not cause symptoms of estrogen deprivation., Conclusions: IGF-I inhibition by pasireotide, acting through the IGF-1R, was associated with decreased proliferation and increased apoptosis in pre-malignant breast lesions and one DCIS. Assuming hyperglycemia can be controlled, these data suggest that inhibiting the IGF-I pathway may prove an effective alternative for breast cancer chemoprevention., Trial Registration: NCT01372644 Trial date: July 1, 2007.