Whole genome sequencing in transposition of the great arteries and associations with clinically relevant heart, brain and laterality genes.

BACKGROUND: The most common cyanotic congenital heart disease (CHD) requiring management as a neonate is transposition of great arteries (TGA). Clinically, up to 50% of TGA patients develop some form of neurodevelopmental disability (NDD), thought to have a significant genetic component. A "ciliopathy" and links with laterality disorders have been proposed. This first report of whole genome sequencing in TGA, sought to identify clinically relevant variants contributing to heart, brain and laterality defects. METHODS: Initial whole genome sequencing analyses on 100 TGA patients focussed on established disease genes related to CHD (n = 107), NDD (n = 659) and heterotaxy (n = 74). Single variant as well as copy number variant analyses were conducted. Variant pathogenicity was assessed using the American College of Medical Genetics and Genomics-Association for Molecular Pathology guidelines. RESULTS: Fifty-five putatively damaging variants were identified in established disease genes associated with CHD, NDD and heterotaxy; however, no clinically relevant variants could be attributed to disease. Notably, case-control analyses identified significantly more predicted-damaging, silent and total variants in TGA cases than healthy controls in established CHD genes (P < .001), NDD genes (P < .001) as well as across the three gene panels (P < .001). CONCLUSION: We present compelling evidence that the majority of TGA is not caused by monogenic rare variants and is most likely oligogenic and/or polygenic in nature, highlighting the complex genetic architecture and multifactorial influences on this CHD sub-type and its long-term sequelae. Assessment of variant burden in key heart, brain and/or laterality genes may be required to unravel the genetic contributions to TGA and related disabilities.

Enhanced antibacterial properties and the cellular response of stainless steel through friction stir processing.

Biofilm related bacterial infection is one of the primary causes of implant failure. Limiting bacterial adhesion and colonization of pathogenic bacteria is a challenging task in health care. Here, a highly simplistic processing technique for imparting antibacterial properties on a biomedical grade stainless steel is demonstrated. Low-temperature high strain-rate deformation achieved using submerged friction stir processing resulted in a nearly single phase ultra-fine grain structure. The processed stainless steel demonstrated improved antibacterial properties for both Gram-positive and Gram-negative bacteria, significantly impeding biofilm formation during the in vitro study. Also, the processed stainless steel showed better compatibility with human fibroblasts manifested through apparent cell spreading and proliferation. The substantial antibacterial properties of the processed steel are explained in terms of the favorable electronic characteristics of the metal-oxide and by using classical Derjaguin-Landau-Verwey-Overbeek (DLVO) and the extended DLVO (XDLVO) approach at the cell-substrate interface.

Oxygen-Vacancy Abundant Nanoporous Ni/NiMnO3/MnO2@NiMn Electrodes with Ultrahigh Capacitance and Energy Density for Supercapacitors.

High-performance energy storage devices (HPEDs) play a critical role in the realization of clean energy and thus enable the overarching pursuit of nonpolluting, green technologies. Supercapacitors are one class of such lucrative HPEDs; however, a serious limiting factor of supercapacitor technology is its sub-par energy density. This report presents hitherto unchartered pathway of physical deformation, chemical dealloying, and microstructure engineering to produce ultrahigh-capacitance, energy-dense NiMn alloy electrodes. The activated electrode delivered an ultrahigh specific-capacitance of 2700 F/cm3 at 0.5 A/cm3. The symmetric device showcased an excellent energy density of 96.94 Wh/L and a remarkable cycle life of 95% retention after 10,000 cycles. Transmission electron microscopy and atom probe tomography studies revealed the evolution of a unique hierarchical microstructure comprising fine Ni/NiMnO3 nanoligaments within MnO2-rich nanoflakes. Theoretical analysis using density functional theory showed semimetallic nature of the nanoscaled oxygen-vacancy-rich NiMnO3 structure, highlighting enhanced carrier concentration and electronic conductivity of the active region. Furthermore, the geometrical model of NiMnO3 crystals revealed relatively large voids, likely providing channels for the ion intercalation/de-intercalation. The current processing approach is highly adaptable and can be applied to a wide range of material systems for designing highly efficient electrodes for energy-storage devices.

Enhanced antibacterial properties on superhydrophobic micro-nano structured titanium surface.

Micro/nano scale surface modifications of titanium based orthopedic and cardiovascular implants has shown to augment biocompatibility. However, bacterial infection remains a serious concern for implant failure, aggravated by increasing antibiotic resistance and over usage of antibiotics. Bacteria cell adhesion on implant surface leads to colonization and biofilm formation resulting in morbidity and mortality. Hence, there is a need to develop new implant surfaces with high antibacterial properties. Recent developments have shown that superhydrophobic surfaces prevent protein and bacteria cell adhesion. In this study, a thermochemical treatment was used modify the surface properties for high efficacy antibacterial activity on titanium surface. The modification led to a micro-nano surface topography and upon modification with polyethylene glycol (PEG) and silane the surfaces were superhydrophilic and superhydrophobic, respectively. The modified surfaces were characterized for morphology, wettability, chemistry, corrosion resistance and surface charge. The antibacterial capability was characterized with Staphylococcus aureus and Escherichia coli by evaluating the bacteria cell inhibition, adhesion kinetics, and biofilm formation. The results indicated that the superhydrophobic micro-nano structured titanium surface reduced bacteria cell adhesion significantly (>90%) and prevented biofilm formation compared to the unmodified titanium surface after 24 h of incubation.

Feeding Neonates and Infants Prior to Surgery for Congenital Heart Defects: Systematic Review and Meta-Analysis.

BACKGROUND: Necrotising enterocolitis (NEC) is a significant cause of mortality and morbidity in neonates requiring cardiac surgery. Feeding practices vary significantly across institutions and remain controversial. We conducted a systematic review of the literature and a meta-analysis to identify associations between feeding practices and necrotising enterocolitis. METHODS: This study was carried out in accordance with the PRISMA guidelines. A literature search was performed in November 2022 using the Cochrane Central Register, Embase, and Pubmed. Two investigators then independently retrieved eligible manuscripts considered suitable for inclusion. Data extracted included gestational age, birth weight, sex, nature of congenital heart lesion, type of operation performed, time on ventilator, ICU stay, hospital stay, post-operative feeding strategy, and complications. The methodological quality was assessed using the Downs and Black score for all randomised control trials and observational studies. RESULTS: The initial search yielded 92 studies. After removing duplicates, there were 85 abstracts remaining. After excluding ineligible studies, 8 studies were included for the meta-analysis. There was no significant risk of NEC associated with pre-operative feeding [OR = 1.22 (95% CI 0.77,1.92)] or umbilical artery catheter placement [OR = 0.91 (95% CI 0.44, 1.89)] and neither outcome exhibited heterogeneity [I2 = 8% and 0%, respectively]. There was a significant association between HLHS and NEC [OR = 2.56 (95% CI 1.56, 4.19)] as well as prematurity and NEC [OR 3.34 (95% CI 1.94, 5.75)] and neither outcome exhibited heterogeneity [I2 = 0% and 0%, respectively]. CONCLUSIONS: There was no association between NEC and pre-operative feeding status in neonates awaiting cardiac surgery. Pre-operative feeding status was not associated with prolonged hospital stay or need for tube assisted feeding at discharge. HLHS and prematurity were associated with increased incidence of NEC.

Facile and Green Engineering Approach for Enhanced Corrosion Resistance of Ni-Cr-Al2O3 Thermal Spray Coatings.

Thermal spray coatings (TSCs) are widely utilized for limiting degradation of structural components. However, the performance of TSCs is significantly impaired by its inherent non-homogeneous microstructure, comprising of splat boundaries, porosities, secondary phase-formation, and elemental segregation. Herein, we report a simplistic approach for significantly enhancing the corrosion resistance of TSCs. Ni-Cr-5Al2O3 coatings were deposited on stainless steel using high-velocity oxy-fuel technique. The microstructure of as-sprayed coating showed significant inhomogeneities in the form of isolated splats and elemental segregation. The microstructure of developed coatings was modified using a novel processing technique, known as stationary friction processing (SFP). The SFP treatment resulted in complete refinement of coating microstructure with elimination of splat boundaries and pores along with elemental homogenization. The corrosion behavior of as-sprayed and SFP treated coating was evaluated in 3.5% NaCl solution using potentiodynamic polarization and electrochemical impedance spectroscopy. The SFP treatment reduced the corrosion rate of as-sprayed coating by an order of magnitude. Long-time immersion studies showed continuously decreasing impedance of the as-sprayed coating due to the penetration of the electrolyte along the splat boundaries. In contrast, impedance for the SFP treated coating increased with the immersion time due to the removal of all microstructural defects.

Enhanced Biocorrosion Resistance and Cellular Response of a Dual-Phase High Entropy Alloy through Reduced Elemental Heterogeneity.

The leaching out of toxic elements from metallic bioimplants has serious repercussions, including allergies, peripheral neuritis, cancer, and Alzheimer's disease, leading to revision or replacement surgeries. The development of advanced structural materials with excellent biocompatibility and superior corrosion resistance in the physiological environment holds great significance. High entropy alloys (HEAs) with a huge compositional design space and outstanding mechanical and functional properties can be promising for bioimplant applications. However, microstructural heterogeneity arising from elemental segregation in these multiprinciple alloy systems is the Achilles heel in the development of next-generation HEAs. Here, we demonstrate a pathway to homogenize the microstructure of a biocompatible dual-phase HEA, comprising refractory elements, namely, MoNbTaTiZr, through severe surface deformation using stationary friction processing (SFP). The strain and temperature field during processing homogenized the elemental distribution, which was otherwise unresponsive to conventional annealing treatments. Nearly 15 min of the SFP treatment resulted in a significant elemental homogenization across dendritic and interdendritic regions, similar to a week-long annealing treatment at 1275 K. The SFP processed alloy showed a nearly six times higher biocorrosion resistance compared to its as-cast counterpart. X-ray photoelectron spectroscopy was used to investigate the nature of the oxide layer formed on the specimens. Superior corrosion behavior of the processed alloy was attributed to the formation of a stable passive layer with zirconium oxide as the primary constituent and higher hydrophobicity. Biocompatibility studies performed using the human mesenchymal stem cell line, showed higher viability for the processed HEA compared to its as-cast counterpart as well as conventional metallic biomaterials including stainless steel (SS316L) and titanium alloy (Ti6Al4V).

Universal implantation of temporary epicardial pacing wires after surgery for congenital heart disease: necessity or luxury?

OBJECTIVES: Routine implantation of temporary epicardial pacing wires after surgery for congenital heart disease (CHD) has recently been questioned. We evaluated the incidence of arrhythmias, arrhythmias causing haemodynamic compromise and the safety of a strategy of selective implantation of pacing wires in our unit. METHODS: All patients who underwent surgery for CHD using cardiopulmonary bypass between September 2015 and December 2016 were retrospectively enrolled in the study (n = 313). Patients were stratified into group A (universal implantation) and group B (selective implantation). Group B received pacing wires only when postoperative rhythm disturbances were anticipated based on the operating surgeon's judgement. The primary outcome was arrhythmia causing haemodynamic compromise. Outcomes were compared between unmatched and propensity matched groups. RESULTS: Forty-eight patients experienced an arrhythmia causing haemodynamic compromise (15.3%). Twenty-three patients (7.3%) experienced an arrhythmia causing haemodynamic compromise that required the use of pacing wires for therapeutic purposes (group A n = 13, group B n = 10, P = 0.34). There were no pacing wire related complications in either group. All patients in group A and 90% in group B had pacing wires when needed (P = 0.435). In group A, 89% of patients had pacing wires which were not used compared with 13% in group B (P < 0.001). Results were unchanged when repeated using propensity matching (81 pairs). CONCLUSIONS: The probability of developing a postoperative arrhythmia requiring therapeutic pacing can be predicted using the risk factors identified in our study. The routine implantation of pacing wires after surgery for CHD is not necessary. A measured reduction from universal implantation is safe.

Postoperative catecholamine resistance following fetal methamphetamine exposure.

Methamphetamine and its related compounds are among the most widely abused recreational drugs worldwide. While a myriad of clinical complications of methamphetamine use have been described, there is a paucity of literature regarding the effects of maternal abuse during pregnancy on neonatal hearts. In this report, we describe a neonate who underwent Norwood-type palliation and subsequently developed catecholamine-resistant cardiogenic shock, likely related to methamphetamine exposure, which recovered after a period of venoarterial extracorporeal membrane oxygenation support.

Two Ventricles Are Not Better Than One in the Fontan Circulation: Equivalent Late Outcomes.

BACKGROUND: A subset of patients who underwent Fontan operations has two adequate-sized ventricles, but an anatomic biventricular circulation cannot be achieved because of complex morphology or for technical reasons. This study sought to determine whether these patients with two-ventricle Fontan circulation had superior outcomes compared with those with a single ventricle. METHODS: A binational Fontan Registry of patients (n = 1,377) was analyzed to identify those patients with two adequate ventricles. This cohort was compared with patients with single-ventricle Fontan circulation. The primary end point was a composite end point called "Fontan failure" encompassing death, heart transplantation, Fontan takedown or conversion, protein-losing enteropathy, plastic bronchitis, or New York Heart Association functional class III or IV. RESULTS: A total of 79 Fontan patients with two adequate ventricles (2V) were compared with 1,291 single ventricle (1V) Fontan patients. Median follow-up for the entire cohort was 11.5 years (interquartile range, 5.1 to 18.8 years). There was no difference in unadjusted 15-year freedom from Fontan failure (2V: 81% [95% confidence interval (CI), 69% to 94%] vs 1V: 86% [95% CI, 83% to 88%], p = 0.4). Propensity-score matching for potential confounding factors yielded 75 two-ventricle Fontan patients matched with 604 single-ventricle Fontan patients, in which 15-year freedom from Fontan failure was also not different (2V: 79% [95% CI, 67% to 94%] vs 1V: 87% [95% CI, 84% to 91%], p = 0.3). CONCLUSIONS: The two-ventricle Fontan circulation does not have better outcomes compared with the single-ventricle Fontan circulation. Late outcomes may depend more on other characteristics of the Fontan circulation. This finding is relevant when the Fontan procedure is being considered as an alternative to anatomic repair in patients with complex two-ventricle morphologies.

Impact of High-Risk Characteristics in Hypoplastic Left Heart Syndrome.

BACKGROUND: Management of hypoplastic left heart syndrome (HLHS) presents many challenges. We describe our institutional outcomes for management of patients with HLHS over the past 12 years and highlight our strategy for those with highly restrictive/intact interatrial septum (R/I-IAS). METHODS: Eighty-eight neonates with HLHS underwent surgical treatment, divided equally into Era-I (n = 44, April 2006 to February 2013) and Era-II (n = 44, March 2013 to June 2018). Up to 2013, all patients with R/I-IAS were delivered at an adjacent adult hospital and then moved to our hospital for intensive care and management. From 2014, these patients were delivered at a co-located theatre in our hospital with immediate atrial septectomy. The hybrid approach was occasionally used with preference for the Norwood procedure for suitable candidates. RESULTS: One-year survival after Norwood procedure was 62.5% and 80% for Era-I and Era-II (P = not significant (ns)), respectively, and 41% of patients were categorized as high risk using conventional criteria. Survival at 1 year differed significantly between high-risk and standard-risk patients (P = 0.01). For high-risk patients, survival increased from 42% to 65% between eras (P = ns). In the R/I-IAS subgroup (n = 15), 11 underwent Norwood procedure after emergency atrial septectomy. Of these, seven born at the adjacent adult hospital had 40% survival to stage II versus 60% for the four born at the colocated theatre. Delivery in a colocated theatre reduced the birth-to-cardiopulmonary bypass median time from 445 (150-660) to 62 (52-71) minutes. CONCLUSION: Reported surgical outcomes are comparable to multicenter reports and international databases. Proactive management for risk factors such as R/I-IAS may contribute to improved overall outcomes.