FANCM interacts with the MHF1-MHF2 complex to limit crossover frequency during rice meiosis.

Crossovers (COs) are necessary for generating genetic diversity that breeders can select, but there are conserved mechanisms that regulate their frequency and distribution. Increasing CO frequency may raise the efficiency of selection by increasing the chance of integrating more desirable traits. In this study, we characterize rice FANCM and explore its functions in meiotic CO control. FANCM mutations do not affect fertility in rice, but they cause a great boost in the overall frequency of COs in both inbred and hybrid rice, according to genetic analysis of the complete set of fancm zmm (hei10, ptd, shoc1, mer3, zip4, msh4, msh5, and heip1) mutants. Although the early homologous recombination events proceed normally in fancm, the meiotic extra COs are not marked with HEI10 and require MUS81 resolvase for resolution. FANCM depends on PAIR1, COM1, DMC1, and HUS1 to perform its functions. Simultaneous disruption of FANCM and MEICA1 synergistically increases CO frequency, but it is accompanied by nonhomologous chromosome associations and fragmentations. FANCM interacts with the MHF complex, and ablation of rice MHF1 or MHF2 could restore the formation of 12 bivalents in the absence of the ZMM gene ZIP4. Our data indicate that unleashing meiotic COs by mutating any member of the FANCM-MHF complex could be an effective procedure to accelerate the efficiency of rice breeding.

RAD51C-RAD51D interplays with MSH5 and regulates crossover maturation in rice meiosis.

Meiotic crossovers ensure accurate chromosome segregation and increase genetic diversity. RAD51C and RAD51D play an early role in facilitating RAD51 during homologous recombination. However, their later function in meiosis is largely unknown in plants. Here, through targeted disruption of RAD51C and RAD51D, we generated three new mutants and revealed their later meiotic role in crossover maturation. The rad51c-3 and rad51d-4 mutants showed a mixture of bivalents and univalents and no chromosomal entanglements, whereas rad51d-5 exhibited an intermediate phenotype with reduced chromosomal entanglements and increased bivalent formation compared with knockout alleles. Comparisons of RAD51 loadings and chromosomal entanglements in these single mutants, rad51c-3 rad51d-4, rad51c-3 dmc1a dmc1b, and rad51d-4 dmc1a dmc1b suggest that the retained level of RAD51 in mutants is required for uncovering their function in crossover formation. Reductions in chiasma frequency and later HEI10 foci in these mutants support that crossover maturation requires RAD51C and RAD51D. Moreover, interaction between RAD51D and MSH5 indicates that RAD51 paralogs may cooperate with MSH5 to ensure accurate Holliday junction processing into crossover products. This finding of the role of RAD51 paralogs in crossover control may be conserved from mammals to plants and advances our current understanding of these proteins.

Replication protein A large subunit (RPA1a) limits chiasma formation during rice meiosis.

Replication protein A (RPA), a single-stranded DNA-binding protein, plays essential role in homologous recombination. However, because deletion of RPA causes embryonic lethality in mammals, the exact function of RPA in meiosis remains unclear. In this study, we generated an rpa1a mutant using CRISPR/Cas9 technology and explored its function in rice (Oryza sativa) meiosis. In rpa1a, 12 bivalents were formed at metaphase I, just like in wild-type, but chromosome fragmentations were consistently observed at anaphase I. Fluorescence in situ hybridization assays indicated that these fragmentations were due to the failure of the recombination intermediates to resolve. Importantly, the mutant had a highly elevated chiasma number, and loss of RPA1a could completely restore the 12 bivalent formations in the zmm (for ZIP1-4, MSH4/5, and MER3) mutant background. Protein-protein interaction assays showed that RPA1a formed a complex with the methyl methansulfonate and UV sensitive 81 (and the Fanconi anemia complementation group M-Bloom syndrome protein homologs (RECQ4A)-Topoisomerase3α-RecQ-mediated genome instability 1 complex to regulate chiasma formation and processing of the recombination intermediates. Thus, our data establish a pivotal role for RPA1a in promoting the accurate resolution of recombination intermediates and in limiting redundant chiasma formation during rice meiosis.

OsMTOPVIB is required for meiotic bipolar spindle assembly.

The organization of microtubules into a bipolar spindle is essential for chromosome segregation. Both centrosome and chromatin-dependent spindle assembly mechanisms are well studied in mouse, Drosophila melanogaster, and Xenopus oocytes; however, the mechanism of bipolar spindle assembly in plant meiosis remains elusive. According to our observations of microtubule assembly in Oryza sativa, Zea mays, Arabidopsis thaliana, and Solanum lycopersicum, we propose that a key step of plant bipolar spindle assembly is the correction of the multipolar spindle into a bipolar spindle at metaphase I. The multipolar spindles failed to transition into bipolar ones in OsmtopVIB with the defect in double-strand break (DSB) formation. However, bipolar spindles were normally assembled in several other mutants lacking DSB formation, such as Osspo11-1, pair2, and crc1, indicating that bipolar spindle assembly is independent of DSB formation. We further revealed that the mono-orientation of sister kinetochores was prevalent in OsmtopVIB, whereas biorientation of sister kinetochores was frequently observed in Osspo11-1, pair2, and crc1 In addition, mutations of the cohesion subunit OsREC8 resulted in biorientation of sister kinetochores as well as bipolar spindles even in the background of OsmtopVIB Therefore, we propose that biorientation of the kinetochore is required for bipolar spindle assembly in the absence of homologous recombination.

PRD1, a homologous recombination initiation factor, is involved in spindle assembly in rice meiosis.

The bipolar spindle structure in meiosis is essential for faithful chromosome segregation. PUTATIVE RECOMBINATION INITIATION DEFECT 1 (PRD1) previously has been shown to participate in the formation of DNA double strand breaks (DSBs). However, the role of PRD1 in meiotic spindle assembly has not been elucidated. Here, we reveal by both genetic analysis and immunostaining technology that PRD1 is involved in spindle assembly in rice (Oryza sativa) meiosis. We show that DSB formation and bipolar spindle assembly are disturbed in prd1 meiocytes. PRD1 signals display a dynamic pattern of localization from covering entire chromosomes at leptotene to congregating at the centromere region after leptotene. Centromeric localization of PRD1 signals depends on the organization of leptotene chromosomes, but not on DSB formation and axis establishment. PRD1 exhibits interaction and co-localization with several kinetochore components. We also find that bi-orientation of sister kinetochores within a univalent induced by mutation of REC8 can restore bipolarity in prd1. Furthermore, PRD1 directly interacts with REC8 and SGO1, suggesting that PRD1 may play a role in regulating the orientation of sister kinetochores. Taken together, we speculate that PRD1 promotes bipolar spindle assembly, presumably by modulating the orientation of sister kinetochores in rice meiosis.

Interstage Survival for Patients with Hypoplastic Left Heart Syndrome After ECMO.

There is a reported 5-20 % incidence of extracorporeal membrane oxygenation (ECMO) following stage I palliation for hypoplastic left heart syndrome (HLHS). This study compares the interstage mortality of HLHS patients supported with ECMO (HLHS-ECMO) to those who were not supported with ECMO (HLHS-nECMO) using the National Pediatric Cardiology Quality Improvement Initiative database. Patients with HLHS who survived to hospital discharge after stage I palliation were analyzed. HLHS-ECMO patients were compared to HLHS-non-ECMO patients with respect to demographics, surgical variables, and interstage survival. A total of 931 patients were identified in the database. Sixty-six (7.1 %) patients were supported with ECMO during their stage I palliation admission. There were no statistically significant differences between the groups with respect to demographics or anatomic subtype. HLHS-ECMO patients were more likely to have a preoperative risk factor identified (62 vs. 48 %, p = 0.03) or require ECMO prior to stage I palliation (3 vs. 0.5 %, p = 0.03). HLHS-ECMO patients had a significantly higher incidence of death or transplant versus the HLHS-nECMO group (18 vs. 9 %, p = 0.03). Despite survival to discharge, patients with HLHS requiring ECMO after their palliation continue to have an increased risk of death/cardiac transplant versus patients that do not require ECMO. ECMO use is likely a marker for a high-risk patient group. These patients may benefit from closer follow-up during the interstage period.

Echocardiographic right ventricular function correlations with cardiac catheterisation data in biventricular congenital heart patients.

BACKGROUND: Newer echocardiographic techniques may allow for more accurate assessment of right ventricular function. Adult studies have correlated these echocardiographic measurements with invasive data, but minimal data exist in the paediatric congenital heart population. The purpose of this study was to evaluate echocardiographic measurements that correlate best with right ventricular systolic and diastolic catheterisation parameters. METHODS: Patients with two-ventricle physiology who underwent simultaneous echocardiogram and cardiac catheterisation were included in this study. Right ventricular systolic echocardiographic data included fractional area change, displacement, tissue Doppler imaging s' wave, global longitudinal strain, and strain rate s' wave. Diastolic echocardiographic data included tricuspid E and A waves, tissue Doppler imaging e' and a' waves, and strain rate e' and a' waves. E/tissue Doppler imaging e', tissue Doppler imaging e'/tissue Doppler imaging a', E/strain rate e', and strain rate e'/strain rate a' ratios were also calculated. Catheterisation dP/dt was used as a marker for systolic function and right ventricular end-diastolic pressure for diastolic function. RESULTS: A total of 32 patients were included in this study. The median age at catheterisation was 3.1 years (0.3-17.6 years). The DP/dt was 493±327 mmHg/second, and the right ventricular end-diastolic pressure was 7.7±2.4 mmHg. There were no significant correlations between catheterisation dP/dt and systolic echocardiographic parameters. Right ventricular end-diastolic pressure correlated significantly with strain rate e' (r=-0.4, p=0.02), strain rate a' (r=-0.5, p=0.03), and E/tissue Doppler imaging e' (r=0.4, p=0.04). CONCLUSION: Catheterisation dP/dt did not correlate with echocardiographic measurements of right ventricular systolic function. Strain rate and tissue Doppler imaging analysis significantly correlated with right ventricular end-diastolic pressure. These values should be further studied to determine whether they may be used as an alternative method to estimate right ventricular end-diastolic pressure in this patient population.

Results of a Feeding Protocol in Patients Undergoing the Hybrid Procedure.

Neonates with single-ventricle physiology are at increased risk of developing gastrointestinal morbidities. Feeding protocols in this patient population have been shown to decrease feeding complications after the Norwood procedure, but no data exist to determine the effectiveness of a feeding protocol in patients undergoing the hybrid procedure. Goal of this study was to examine the impact of a standardized feeding protocol on the incidence of overall postoperative gastrointestinal morbidity after the hybrid procedure. Retrospective chart review was performed on neonates undergoing the hybrid procedure. Neonates were divided into two groups, pre-feeding protocol (pre-FP), which encompassed the years 2002-2008, and post-feeding protocol (post-FP), which encompassed the years 2011-2014. Preoperative, operative, and postoperative data were collected. T test or Fisher's exact test was used for analysis. p < 0.05 was considered significant. Seventy-three neonates were in the pre-FP and 52 neonates were in the post-FP. There were no significant differences between the pre-FP and the post-FP in cardiac diagnosis (62 HLHS, 11 other vs. 39 HLHS, 13 other, respectively). Pre-FP underwent hybrid procedure later than the post-FP (9.1 ± 5.8 vs. 5.7 ± 3.4 days, respectively, p < 0.01) and achieved full enteral feeds earlier than the post-FP (3.2 + 2.9 vs. 7.8 + 3.9 days, respectively, p < 0.01). The incidence of necrotizing enterocolitis was higher in the pre-FP versus post-FP [11.0 % (8/65) vs. 5.8 % (3/49), respectively, p = 0.36]. Though not significant, the incidence of necrotizing enterocolitis decreased by almost 50 % after initiating a feeding protocol in patients undergoing the hybrid procedure. This is consistent with previous studies showing beneficial results of a feeding protocol in this complex patient population.

Arrhythmias After Stage I Hybrid Palliation in Single-Ventricle Patients.

The hybrid procedure is an alternative palliative strategy for patients with single-ventricle physiology. No data exist documenting the incidence of arrhythmias after the hybrid procedure. Goal of this study was to determine the incidence and type of arrhythmias in patients undergoing the hybrid procedure. A retrospective chart review was performed including all patients undergoing the hybrid procedure between January of 2010 through December of 2013. Sixty-five patients underwent the hybrid procedure during this time period (43 HLHS, 22 other). Average gestational age at admission was 37.7 weeks. Average age at time of procedure was 7.6 days. Five patients had documented arrhythmias (7.7 %). Four were supraventricular tachycardias, and 1 was a sinus bradycardia. One patient with arrhythmia died during hospitalization, and another patient with arrhythmia died during the interstage period. Hybrid palliation for patients with single-ventricle physiology has a low incidence of arrhythmias. In this cohort of patients, arrhythmias did not contribute to mortality. There was a trend toward association between arrhythmias and longer total length of hospital stay.

Minimally Invasive Aortic Valve Replacement: Cost-Benefit Analysis of Ministernotomy Versus Minithoracotomy Approach.

BACKGROUND AND AIM OF THE STUDY: Minimally invasive aortic valve replacement via ministernotomy (ministernotomy-AVR) or minithoracotomy (minithoracotomy-AVR) is gaining popularity. To date, a direct comparison of ministernotomy-AVR versus minithoracotomy-AVR is lacking. The study aim was to compare these two procedures from a cost-benefit perspective. METHODS: Eight reports from the United States were selected from amongst 33,494 literature citations based on sample size and data completeness. Perioperative variables were collected for each surgical approach. Fixed and variable costs were estimated as cost per case in excess of full sternotomy AVR procedures. RESULTS: Ministernotomy-AVR patients were of a significantly lower mean age (59.8 years versus 67.9 years), ejection fraction (50.4-51.6% versus 56.1-57.8%), shorter cardiopulmonary bypass time (97.2 min versus 125.6 min) and cross-clamp time (69.9 min versus 87.9 min), a lower rate of blood transfusion (25.9% versus 64.4%), and a shorter length of hospital stay (5.7 versus 6.2 days). There were no significant inter-group differences in 30-day mortality, conversion to sternotomy, neurologic events, arrhythmia, wound infection, or postoperative bleeding. Assuming a volume of 50 cases per year, the added operative cost per case for a minithoracotomy-AVR was US$ 4,254 compared to US$ 290 for a ministernotomy-AVR. The added costs per case, assuming 200 cases per year, were US$ 4,209 and US$ 290, respectively. A minithoracotomy-AVR program performing 50 cases per year adds US$ 1,063,665 of operative costs over five years, compared to US$ 72,500 for a ministernotomy-AVR program. CONCLUSION: The present analysis suggested that the clinical benefits of ministernotomy-AVR are comparable or better than those of minithoracotomy-AVR, and at lower costs. Healthcare delivery organizations should consider the results of cost-benefit examinations when developing surgical valve replacement programs.

SCC3 is an axial element essential for homologous chromosome pairing and synapsis.

Cohesin is a multi-subunit protein that plays a pivotal role in holding sister chromatids together during cell division. Sister chromatid cohesion 3 (SCC3), constituents of cohesin complex, is highly conserved from yeast to mammals. Since the deletion of individual cohesin subunit always causes lethality, it is difficult to dissect its biological function in both mitosis and meiosis. Here, we obtained scc3 weak mutants using CRISPR-Cas9 system to explore its function during rice mitosis and meiosis. The scc3 weak mutants displayed obvious vegetative defects and complete sterility, underscoring the essential roles of SCC3 in both mitosis and meiosis. SCC3 is localized on chromatin from interphase to prometaphase in mitosis. However, in meiosis, SCC3 acts as an axial element during early prophase I and subsequently situates onto centromeric regions following the disassembly of the synaptonemal complex. The loading of SCC3 onto meiotic chromosomes depends on REC8. scc3 shows severe defects in homologous pairing and synapsis. Consequently, SCC3 functions as an axial element that is essential for maintaining homologous chromosome pairing and synapsis during meiosis.

RETINOBLASTOMA RELATED 1 switches mitosis to meiosis in rice.

The transition from mitosis to meiosis is a critical event in the reproductive development of all sexually reproducing species. However, the mechanisms that regulate this process in plants remain largely unknown. Here, we find that the rice (Oryza sativa L.) protein RETINOBLASTOMA RELATED 1 (RBR1) is essential to the transition from mitosis to meiosis. Loss of RBR1 function results in hyper-proliferative sporogenous-cell-like cells (SCLs) in the anther locules during early stages of reproductive development. These hyper-proliferative SCLs are unable to initiate meiosis, eventually stagnating and degrading at late developmental stages to form pollen-free anthers. These results suggest that RBR1 acts as a gatekeeper of entry into meiosis. Furthermore, cytokinin content is significantly increased in rbr1 mutants, whereas the expression of type-B response factors, particularly LEPTO1, is significantly reduced. Given the known close association of cytokinins with cell proliferation, these findings imply that hyper-proliferative germ cells in the anther locules may be attributed to elevated cytokinin concentrations and disruptions in the cytokinin pathway. Using a genetic strategy, the association between germ cell hyper-proliferation and disturbed cytokinin signaling in rbr1 has been confirmed. In summary, we reveal a unique role of RBR1 in the initiation of meiosis; our results clearly demonstrate that the RBR1 regulatory module is connected to the cytokinin signaling pathway and switches mitosis to meiosis in rice.

Length of stay and treatment-related complications are similar in pediatric and AYA patients with bone sarcoma in United States children's hospitals.

BACKGROUND: Adolescent and young adult (AYA) cancer patients have been shown to have unique clinical characteristics and inferior outcomes compared to younger patients. More than 2,500 new bone sarcomas are diagnosed yearly in the US, many of whom are AYAs treated at pediatric hospitals. Pediatric providers must understand the impact of increasing age on complications, costs, and outcomes. The study set-out to determine if AYA patients with bone sarcomas have increased healthcare utilization and treatment-related complications as compared to younger patients. PROCEDURE: Data were obtained from the Pediatric Health Information System for bone sarcoma admissions at 41 US children's hospitals from 2006 to 2010. Patient demographics and morbidities were compared in patients 0-14 and 15-28 years using two sample t-tests, Wilcoxon two sample tests, or chi-squared tests. RESULTS: We identified 835 pediatric and 562 AYA patients with bone sarcomas. Mean length of stay (LOS) was comparable between age groups (4.6 and 4.8 days, P = 0.46), although AYA patients had greater mean pharmaceutical charges ($18,124 vs. $13,637, P < 0.0001). Common treatment-related complications were similar between groups, with the exceptions that febrile neutropenia admissions were more likely in younger patients, and thrombosis, renal failure, and pain were more common in AYA patients. CONCLUSIONS: In US children's hospitals, AYA patients with sarcomas do not have prolonged LOS or an increased risk of the most common treatment-related complications as compared to younger patients. Chronic pain appears to be a greater burden in AYA patients, and may account for their higher inpatient pharmaceutical costs.

The role of different anesthetic techniques in altering the stress response during cardiac surgery in children: a prospective, double-blinded, and randomized study.

OBJECTIVES: Our goal was to evaluate the role of three anesthetic techniques in altering the stress response in children undergoing surgery for repair of congenital heart diseases utilizing cardiopulmonary bypass in the setting of fast tracking or early tracheal extubation. Furthermore, we wanted to evaluate the correlation between blunting the stress response and the perioperative clinical outcomes. DESIGN: Prospective, randomized, double-blinded study. SETTING: Single center from December 2008 to May of 2011. PATIENTS: Forty-eight subjects (low-dose fentanyl plus placebo, n = 16; high-dose fentanyl plus placebo, n = 17; low-dose fentanyl plus dexmedetomidine, n = 15) were studied between ages 30 days to 3 years old who were scheduled to undergo repair for a ventricular septal defect, atrioventricular septal defect, or Tetralogy of Fallot. METHODS: Children undergoing surgical repair of congenital heart disease were randomized to receive low-dose fentanyl (10 mcg/kg; low-dose fentanyl), high-dose fentanyl (25mcg/kg; high-dose fentanyl), or low-dose fentanyl plus dexmedetomidine (as a 1 mcg/kg loading dose followed by infusion at 0.5mcg/kg/hr until separation from cardiopulmonary bypass. In addition, patients received a volatile anesthetic agent as needed to maintain hemodynamic stability. Blood samples were tested for metabolic, hormonal and cytokine markers at baseline, after sternotomy, after the start of cardiopulmonary bypass, at the end of the procedure and at 24 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Forty-eight subjects (low-dose fentanyl plus placebo, n = 16; high-dose fentanyl plus placebo, n = 17; low-dose fentanyl plus dexmedetomidine, n = 15) were studied. Subjects in the low-dose fentanyl plus placebo group had significantly higher levels of adrenocorticotropic hormone, cortisol, glucose, lactate, and epinephrine during the study period. The lowest levels of stress markers were seen in the high-dose fentanyl plus placebo group both over time (adrenocorticotropic hormone, p= 0.01; glucose, p = 0.007) and at individual time points (cortisol and lactate at the end of surgery, epinephrine poststernotomy; p < 0.05). Subjects in the low-dose fentanyl plus dexmedetomidine group had lower lactate levels at the end of surgery compared with the low-dose fentanyl plus placebo group (p < 0.05). Although there were no statistically significant differences in plasma cytokine levels between the three groups, the low-dose fentanyl plus placebo group had significantly higher interleukin-6:interleukin-10 ratio at 24 hours postoperatively (p < 0.0001). In addition, when compared with the low-dose fentanyl plus placebo group, the low-dose fentanyl plus dexmedetomidine group showed a lower norepinephrine level from baseline at poststernotomy, after the start of cardiopulmonary bypass, and at the end of surgery (p ≤ 0.05). Subjects in the low-dose fentanyl plus placebo group had more postoperative narcotic requirement (p = 0.004), higher prothrombin time (p ≤ 0.03), and more postoperative chest tube output (p < 0.05). Success of fast tracking was not significantly different between groups (low-dose fentanyl plus placebo 75%, high-dose fentanyl plus placebo 82%, low-dose fentanyl plus dexmedetomidine 93%; p = 0.39). CONCLUSIONS: The use of low-dose fentanyl was associated with the greatest stress response, most coagulopathy, and highest transfusion requirement among our cohorts. Higher dose fentanyl demonstrated more favorable blunting of the stress response. When compared with low-dose fentanyl alone, the addition of dexmedetomidine improved the blunting of the stress response, while achieving better postoperative pain control.

Metabolic syndrome and endocrine dysfunctions after HSCT in children.

MS and endocrine dysfunction(s) are common well-recognized complications after HSCT. We retrospectively analyzed our data on 160 patients with a median age at transplant of five yr (0.3-23), who had been followed for a median of seven yr (range 3-18) at Nationwide Children's Hospital after transplant. Dyslipidemia and MS were seen in 13% and 7.5% patients, respectively, and 58% of these patients were <20 yr of age. Twelve patients met the criteria for diagnosis of MS, but four of these did not meet the International Diabetic Federation or WHO criteria. Variation in the diagnostic criteria for MS leading to underdiagnosis is discussed. Female gonadal failure (27%) and hypothyroidism (21%) were the most common endocrine dysfunctions, followed by short stature and GH deficiency (17%) each. TBI and younger age at HSCT were associated with the highest burden of long-term effects, and female sex was more significantly associated with MS-related dysfunction (p < 0.05). Uniform diagnostic criteria for MS and close follow-up after transplant are important for the early diagnosis and management of these late effects, thereby improving the overall quality of life of these patients.

Changes in hemodynamic parameters and cerebral saturation during supraventricular tachycardia.

Induced supraventricular tachycardia (SVT) during electrophysiology studies (EPS) can be associated with hemodynamic changes. Traditionally, invasive arterial blood pressure has been used for continuous monitoring of these changes. This prospective study evaluated the efficacy of near-infrared spectroscopy (NIRS) monitoring during SVT. The use of NIRS has expanded with evidence of its accuracy and benefit in detecting cerebral hypoperfusion. This study aimed first to determine the hemodynamic changes associated with electrophysiology testing for SVT and second to determine whether the hemodynamic changes are associated with similar changes in the cerebral saturation as determined by NIRS. The study enrolled 30 patients 5-20 years of age with a history of SVT who underwent an EPS. The demographic data included age, gender, weight, height, and type of SVT. Hemodynamic data (invasive blood pressure and heart rate), NIRS, bispectral index (BIS), end-tidal carbon dioxide, and pulse oximetry were collected before and during three episodes of induced SVT. The linear correlation coefficient (r) was measured to calculate the relationship of the changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) to the changes in NIRS values during the SVT episodes. Data from 22 patients were collected. The induction of SVT was associated mainly with a change in SBP and a less prominent change in DBP and MAP from baseline. The changes in hemodynamic status were associated with minimal changes in cerebral saturations, as evidenced by an average absolute change in NIRS of <1 from baseline value. The changes in hemodynamics were correlated linearly with cerebral saturation. Changes in SBP, DBP, and MAP were correlated positively with changes in NIRS, as denoted by (r) values of 0.52, 0.57, and 0.67 respectively, and a P value less than 0.05 for all three association tests. Induction of SVT during electrophysiology testing is associated with hemodynamic changes, mainly in SBP. In this study, these hemodynamic changes resulted in a minimal decrease in cerebral perfusion, as evidenced by minimal changes in the cerebral saturation measured by NIRS (0.7% from baseline). Although the changes in the cerebral saturation were minimal, these changes were linearly correlated with the changes in the hemodynamics. This study is the first to demonstrate the possible application of NIRS monitoring during EPS and to document that despite changes in the hemodynamic status, the changes in cerebral oxygenation are minimal, thereby confirming the safety of EPS for SVT.

Perception scores of siblings and parents of children with hypoplastic left heart syndrome.

OBJECTIVES: Siblings of children with chronic medical conditions endorse a lower quality of life compared to age-matched peers. Caregiver and sibling-self report of adjustment are often discordant. Congenital heart disease significantly affects family life. To date, there have been no studies addressing the functioning of siblings of children with hypoplastic left heart syndrome, one of the most severe forms of congenital heart disease. The goal of this study was to assess the impact of hypoplastic left heart syndrome on sibling's quality of life as well as the caregiver's perception of this effect. STUDY DESIGN: Cross-sectional study using a web-based survey distributed via various listservs targeted towards families of children with hypoplastic left heart syndrome. Employed the Sibling Perception Questionnaire, designed to assess sibling and caregiver perceptions of adjustment to chronic illness. A Negative Adjustment Composite Score was calculated for each respondent, with higher values representing more negative adjustment. RESULTS: Thirty-five caregivers responded. Majority of caregivers were female (74%), white (86%) and college educated (54%). Thirty-two siblings participated, ranging in age from 7 to 30 years of age (12.5 ± 6.3). Most children with hypoplastic left heart syndrome (73%) had undergone the third stage of palliation. Forty-two caregiver-sibling pairs were examined. Caregiver Negative Adjustment Composite Scores were significantly higher than sibling scores, with caregivers reporting more adjustment problems (2.4 ± 0.4) than siblings (2.3 ± 0.3, P < .05). Sibling age was correlated with worse caregiver and sibling scores (r 0.35, P < .05). CONCLUSIONS: Caregivers of children with hypoplastic left heart syndrome perceive their siblings as struggling more than the children self-report. Siblings tend to report worse adjustment as they get older. These data suggest that programs should include support for the entire family through all ages to optimize quality of life.

Isolated heart transplant and combined heart-liver transplant in adult congenital heart disease patients: Insights from the united network of organ sharing.

BACKGROUND/METHODS: The aging patient with severe congenital heart disease (CHD) faces many challenges: heart failure, arrhythmia, and in the Fontan patient, liver disease. Our goal was to define combined heart liver transplant (CHLT) and isolated orthotopic heart transplant (OHT) outcomes in U.S. adult CHD patients. The U.S. United Network for Organ Sharing (UNOS) thoracic and liver databases were queried for cardiac and CHD diagnoses, from inception-2014. RESULTS: In CHLT, CHD made up 22% of waitlist patients (non-CHD n=262 vs. CHD n=58), and 20% of transplanted patients (non-CHD n=137 vs. CHD n=27). Liver function tests in the non-CHD and CHD groups were similar and there was no difference in CHD and non-CHD survival (HR 0.93, CI: 0.36-2.38, p 0.48). In isolated OHT, CHD patients comprised 2% of those listed (non-CHD n=74,080 vs. CHD n=1599) and transplanted (non-CHD n=48,985 vs. CHD n=967) and had higher early (<1year) mortality (HR 1.36, CI: 1.18-1.57, p<0.0001), but better long-term survival (HR 0.66, CI; 0.57-0.76, p<0.001) than non-CHD. Both groups benefitted from mechanical support when used (non-CHD HR 0.34, CI: 0.31-0.37 and CHD HR 0.14, CI: 0.03-0.58) and prior sternotomy had no effect on mortality in CHD (HR 0.63, CI: 0.15-2.58). CONCLUSIONS: Survival of CHD patients undergoing CHLT is no different than in non-CHD, encouraging consideration of CHLT when clinically appropriate. Short-term mortality is higher in CHD (vs. non-CHD) patients undergoing OHT, regardless of prior cardiac surgery status. Modifications to CHD classification within UNOS would help better understand CHD CHLT and OHT outcomes.