High expression of oleoyl-ACP hydrolase underpins life-threatening respiratory viral diseases.

Respiratory infections cause significant morbidity and mortality, yet it is unclear why some individuals succumb to severe disease. In patients hospitalized with avian A(H7N9) influenza, we investigated early drivers underpinning fatal disease. Transcriptomics strongly linked oleoyl-acyl-carrier-protein (ACP) hydrolase (OLAH), an enzyme mediating fatty acid production, with fatal A(H7N9) early after hospital admission, persisting until death. Recovered patients had low OLAH expression throughout hospitalization. High OLAH levels were also detected in patients hospitalized with life-threatening seasonal influenza, COVID-19, respiratory syncytial virus (RSV), and multisystem inflammatory syndrome in children (MIS-C) but not during mild disease. In olah-/- mice, lethal influenza infection led to survival and mild disease as well as reduced lung viral loads, tissue damage, infection-driven pulmonary cell infiltration, and inflammation. This was underpinned by differential lipid droplet dynamics as well as reduced viral replication and virus-induced inflammation in macrophages. Supplementation of oleic acid, the main product of OLAH, increased influenza replication in macrophages and their inflammatory potential. Our findings define how the expression of OLAH drives life-threatening viral disease.

Young infants with symptomatic tetralogy of Fallot: Shunt or primary repair?

Objectives: The optimal treatment strategy for symptomatic young infants with tetralogy of Fallot (TOF) is unclear. We sought to compare the outcomes of staged repair (SR) (shunt palliation followed by second-stage complete repair) versus primary repair (PR) at 2 institutions that have exclusively adopted each strategy. Methods: We performed propensity score-matched comparison of 143 infants under 4 months of age who underwent shunt palliation at one institution between 1993 and 2021 with 122 infants who underwent PR between 2004 and 2018 at another institution. The primary outcome was mortality. Secondary outcomes were postoperative complications, durations of perioperative support and hospital stays, and reinterventions. Median follow-up was 8.3 years (interquartile range, 8.1-13.4 years). Results: After the initial procedure, hospital mortality (shunt, 2.8% vs PR, 2.5%; P = .86) and 10-year survival (shunt, 95%; 95% confidence interval [CI], 90%-98% vs PR, 90%; 95% CI, 81%-95%; P = .65) were similar. The SR group had a greater risk of early reinterventions but similar rates of late reinterventions. Propensity score matching yielded 57 well-balanced pairs. In the matched cohort, the SR group had similar freedom from reintervention (55%; 95% CI, 39%-68% vs 59%; 95% CI, 43%-71%; P = .85) and greater survival (98%; 95% CI, 88%-99.8% vs 85%; 95% CI, 69%-93%; P = .02) at 10 years, as the result of more noncardiac-related mortalities in the PR group. Conclusions: In symptomatic young infants with TOF operated at 2 institutions with exclusive treatment protocols, the SR strategy was associated with similar cardiac-related mortality and reinterventions as the PR strategy at medium-term follow-up.

Outcomes of extracardiac Fontan operation: A single institution experience with 398 patients.

OBJECTIVE: The study objective was to evaluate the outcomes of the extracardiac Fontan operation at a single institution. METHODS: We conducted a retrospective study of 398 patients from a single institution who underwent their initial extracardiac Fontan operation between 1997 and 2020. We determined the incidence of and risk factors for failure of the Fontan circulation, which includes death, Fontan takedown, heart transplantation, protein-losing enteropathy, plastic bronchitis, and functional status at the last follow-up. RESULTS: The median follow-up time was 10.3 years (interquartile range, 6.4-14.6). The overall survival was 96% and 86% at 10 and 20 years after extracardiac Fontan operation, respectively. There were 6 early deaths (6/398, 1.5%) and 15 late deaths (15/398, 3.8%). Forty-nine patients (12.5%) developed failure of the Fontan circulation. Freedom from the failure of Fontan circulation was 88% at 10 years and 76% at 20 years. Risk factors for failure of the Fontan circulation were right ventricular dominance (hazard ratio, 4.7; P < .001; 95% CI, 2.1-10.5), aortic atresia (hazard ratio, 5.5; P < .001; 95% CI, 2.3-12.8), and elevated mean pulmonary artery pressure (hazard ratio, 2.3; P = .002; 95% CI, 1.2-6.7). CONCLUSIONS: Rates of failure of the Fontan circulation are low after the contemporary extracardiac Fontan operation. Risk factors for failure of the extracardiac Fontan circulation include right ventricular dominance, aortic atresia, and elevated pulmonary artery pressures.

Heart Transplantation after Univentricular Palliation: Improved Outcomes and Increased Complexity.

AIM: Heart transplantation (HT) in patients with failing univentricular circulation is often challenging. This is compounded by the ever-increasing number of patients with prior Norwood-type reconstruction of the aorta, large aortic root, and often dense adhesions from multiple prior operations. We aimed to elucidate differences in outcomes of HT in patients with prior univentricular palliations, with and without prior Norwood-type aortic arch reconstruction (ArchRec). METHODS: All patients who underwent HT for failed univentricular palliation during the 1990-2022 period were included in the study. RESULTS: Of 45 patients, 18 had undergone ArchRec. Hospital mortality improved in the recent era (17.4% before 2006 vs 0% after 2006; p=0.11), despite a higher proportion of patients with ArchRec (17.4% before 2006 vs 60.8% after 2006, p=0.002). Patients with ArchRec had a higher number of prior cardiac surgeries (4.1±1.5 vs 3.2±1.3, p=0.04), longer cardiopulmonary bypass time (320±23 vs 242±21 min, p=0.02), more concomitant arch reconstruction (33.3% vs 0%, p=0.02), greater need for post-HT extracorporeal membrane oxygenation (33.3% vs 3.7%; p=0.01) and longer hospital stay (37.1±30.5 days vs 23.6±11.8 days, p=0.04). Freedom from death or retransplantation for all patients was 91%, 73%, 67%, and 53% at 1, 5, 10, and 15-years, respectively. Prior ArchRec, Fontan procedure, and earlier eras were not risk factors for death. CONCLUSIONS: The outcomes of HT after univentricular palliation have improved in recent times and low operative mortality can be achieved. Despite increased complexity, good similar outcomes can be achieved in patients with and without prior arch reconstruction regardless of the palliation stage.

Arterial switch operation in a child with commissural malalignment and unusual coronary anatomy.

The arterial switch operation has evolved to become the treatment of choice for transposition of the great arteries and is one of the greatest success stories in congenital heart surgery. The most crucial step of the operation is the coronary artery translocation; therefore, it is of paramount importance for surgeons to know every single detail about the morphology and spatial relationships of the coronary arteries and the roots of the great vessels. However, sometimes the surgeon may face unfavourable scenarios such as major commissural malalignment and anomalous coronary artery patterns and need to be prepared to carry out a successful coronary artery translocation. Herein, we demonstrate that the trapdoor technique is useful for transferring coronary arteries in a neonate with major commissural malalignment and unusual coronary anatomy during the arterial switch operation.

The American Association for Thoracic Surgery (AATS) 2024 expert consensus document: Management of neonates and infants with Ebstein anomaly.

OBJECTIVES: Symptomatic neonates and infants with Ebstein anomaly (EA) require complex management. A group of experts was commissioned by the American Association for Thoracic Surgery to provide a framework on this topic focusing on risk stratification and management. METHODS: The EA Clinical Congenital Practice Standards Committee is a multinational and multidisciplinary group of surgeons and cardiologists with expertise in EA. A citation search in PubMed, Embase, Scopus, and Web of Science was performed using key words related to EA. The search was restricted to the English language and the year 2000 or later and yielded 455 results, of which 71 were related to neonates and infants. Expert consensus statements with class of recommendation and level of evidence were developed using a modified Delphi method, requiring 80% of members votes with at least 75% agreement on each statement. RESULTS: When evaluating fetuses with EA, those with severe cardiomegaly, retrograde or bidirectional shunt at the ductal level, pulmonary valve atresia, circular shunt, left ventricular dysfunction, or fetal hydrops should be considered high risk for intrauterine demise and postnatal morbidity and mortality. Neonates with EA and severe cardiomegaly, prematurity (<32 weeks), intrauterine growth restriction, pulmonary valve atresia, circular shunt, left ventricular dysfunction, or cardiogenic shock should be considered high risk for morbidity and mortality. Hemodynamically unstable neonates with a circular shunt should have emergent interruption of the circular shunt. Neonates in refractory cardiogenic shock may be palliated with the Starnes procedure. Children may be assessed for later biventricular repair after the Starnes procedure. Neonates without high-risk features of EA may be monitored for spontaneous closure of the patent ductus arteriosus (PDA). Hemodynamically stable neonates with significant pulmonary regurgitation at risk for circular shunt with normal right ventricular systolic pressure should have an attempt at medical closure of the PDA. A medical trial of PDA closure in neonates with functional pulmonary atresia and normal right ventricular systolic pressure (>20-25 mm Hg) should be performed. Neonates who are hemodynamically stable without pulmonary regurgitation but inadequate antegrade pulmonary blood flow may be considered for a PDA stent or systemic to pulmonary artery shunt. CONCLUSIONS: Risk stratification is essential in neonates and infants with EA. Palliative comfort care may be reasonable in neonates with associated risk factors that may include prematurity, genetic syndromes, other major medical comorbidities, ventricular dysfunction, or sepsis. Neonates who are unstable with a circular shunt should have emergent interruption of the circular shunt. Neonates who are unstable are most commonly palliated with the Starnes procedure. Neonates who are stable should undergo ductal closure. Neonates who are stable with inadequate pulmonary flow may have ductal stenting or a systemic-to-pulmonary artery shunt. Subsequent procedures after Starnes palliation include either single-ventricle palliation or biventricular repair strategies.

Early outcomes after post-cardiotomy extracorporeal membrane oxygenation in paediatric patients: a contemporary, binational cohort study.

OBJECTIVES: The aim of this study was to assess the early outcomes and risk factors of paediatric patients requiring extracorporeal membrane oxygenation after cardiac surgery (post-cardiotomy). METHODS: Retrospective binational cohort study from the Australia and New Zealand Congenital Outcomes Registry for Surgery database. All patients younger than 18 years of age who underwent a paediatric cardiac surgical procedure from 1 January 2013 to 31 December 2021 and required post-cardiotomy extracorporeal membrane oxygenation (PC-ECMO) in the same hospital admission were included in the study. RESULTS: Of the 12 290 patients included in the study, 376 patients required post-cardiotomy ECMO (3%). Amongst these patients, hospital mortality was 35.6% and two-thirds of patients experienced a major complication. Hypoplastic left heart syndrome was the most common diagnosis (17%). The Norwood procedure and modified Blalock-Taussig shunts had the highest incidence of requiring PC-ECMO (odds ratio of 10 and 6.8 respectively). Predictors of hospital mortality after PC-ECMO included single-ventricle physiology, intracranial haemorrhage and chylothorax. CONCLUSIONS: In the current era, one-third of patients who required PC-ECMO after paediatric cardiac surgery in Australia and New Zealand did not survive to hospital discharge. The Norwood procedure and isolated modified Blalock-Taussig shunt had the highest incidence of requiring PC-ECMO. Patients undergoing the Norwood procedure had the highest mortality (48%). Two-thirds of patients on PC-ECMO developed a major complication.

Long-Term Outcomes of Mechanical Aortic Valve Replacement in Children.

When the options of aortic valve repair or the Ross procedure are not feasible or have been exhausted, mechanical aortic valve replacement (AVR) may provide a reliable and structurally durable alternative, but with the limitations of long-term anticoagulation, thrombosis risk and lack of valve growth potential. In this article, we review the longitudinal outcomes of mechanical AVR in children in our institution and compare them to those recently reported by others. From 1978 to 2020, 62 patients underwent mechanical AVR at a median age of 12.4 years (interquartile range (IQR): 8.6-16.8 years). The most common underlying diagnoses were: conotruncal anomalies (40%, 25/62), congenital aortic stenosis (16%, 10/62), rheumatic valve disease (16%, 10/62), connective tissue disease (8.1%, 5/62) and infective endocarditis (6.5%, 4/62). Thirty-two patients (52%, 32/62) had at least 1 prior aortic valve surgery prior to mechanical AVR. Early death was 3.2% (2/62). Median follow-up was 14.4 years (IQR: 8.4-28.2 years). Kaplan-Meier survival was 96.8%, 91.9%, 86.3%, and 81.9% at 1, 5, 10, and 20 years. On competing risk analysis, the proportion of patients alive without aortic valve reoperation at 1, 5, 10, and 20 years was 95.2%, 87.0%, 75.5% and 55.4%, respectively, while the proportion of patients that had aortic valve reoperation (with death as a competing event) at 1, 5, 10, and 20 years was 1.6%, 4.9%, 12.8%, and 28.5%, respectively. In conclusion, when the options of aortic valve repair or the Ross procedure are not feasible in children, mechanical AVR is an alternative, yet the long-term rates of mortality and need for aortic valve reoperation are of concern.

Methodological optimisation of thymocyte isolation and cryopreservation of human thymus samples.

Premature lymphocytes develop into non-autoreactive, mature naïve CD4+ or CD8+ T cells in the thymus before entering the circulation. However, in-depth characterization of human thymocyte development remains challenging due to limited availability of human thymus samples and the fragile nature of thymocyte populations. Thymocytes often do not survive cryopreservation and thawing procedures, especially the fragile CD4+CD8+ double positive population. It is generally recommended to use fresh human thymus tissue on the day of excision to avoid any biases in thymocyte composition. This hampers the possibility to perform multiple experiments on the same thymus sample. To establish how the thymocyte viability and composition can be maintained, we compared two thymocyte isolation methods used for human and/or mice thymi, three cryopreservation methods in combination with our most gentle thawing technique. Based on our findings we established that fresh human thymi remain viable in cold storage for up to two days post-surgery without compromising thymocyte composition. Thymocytes can be cryopreserved if required, although the CD4+CD8+ double positive populations may be reduced. Our study provides thoroughly optimized methods to study human thymocyte development over a considerable time-frame post-surgery.

Clinical assessment can be lifesaving: Salvage of catastrophic cerebral ischemia by conversion to central extracorporeal membrane oxygenation.

Peripheral veno-artertial extracorporeal membrane oxygenation (VA-ECMO) is commonly used in the paediatric population for intractable respiratory and cardiac failure. One of the devastating complications of VA-ECMO is severe brain damage due to ischemia or haemorrhage. We describe a case of peripheral cervical VA-ECMO complicated by evolving right cerebral ischemia which was rescued with rapid conversion from peripheral to central VA-ECMO support. Notably, the patient had a complete circle of Willis. Following conversion, we observed complete resolution of neurological symptoms with full functional recovery.