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PIK3CA-related overgrowth spectrum (PROS) conditions of the head and neck are treatment challenges. Traditionally, these conditions require multiple invasive interventions, with incomplete malformation removal, disfigurement, and possible dysfunction. Use of the PI3K inhibitor alpelisib, previously shown to be effective in PROS, has not been reported in PIK3CA-associated head and neck lymphatic malformations (HNLMs) or facial infiltrating lipomatosis (FIL). We describe prospective treatment of 5 children with PIK3CA-associated HNLMs or head and neck FIL with alpelisib monotherapy.A total of 5 children with PIK3CA-associated HNLMs (n = 4) or FIL (n = 1) received alpelisib monotherapy (aged 2-12 years). Treatment response was determined by parental report, clinical evaluation, diary/questionnaire, and standardized clinical photography, measuring facial volume through 3-dimensional photos and magnetic resonance imaging.All participants had reduction in the size of lesion, and all had improvement or resolution of malformation inflammation/pain/bleeding. Common invasive therapy was avoided (ie, tracheotomy). After 6 or more months of alpelisib therapy, facial volume was reduced (range 1%-20%) and magnetic resonance imaging anomaly volume (range 0%-23%) were reduced, and there was improvement in swallowing, upper airway patency, and speech clarity.Individuals with head and neck PROS treated with alpelisib had decreased malformation size and locoregional overgrowth, improved function and symptoms, and fewer invasive procedures.

Objective Although the right ventricle (RV) to pulmonary artery conduit in stage 1 Norwood operation results in improved interstage survival, the long-term effects of the ventriculotomy used in the traditional technique remain a concern. The periscopic technique (PT) of RV to pulmonary artery conduit placement has been described as an alternative technique to minimize RV injury. A retrospective study was performed to compare the effects of traditional technique and PT on ventricular function following Norwood operation. Methods A retrospective study of all patients who underwent Norwood operation from 2012 to 2019 was performed. Patients with baseline RV dysfunction and significant tricuspid valve regurgitation were excluded. Prestage 2 echocardiograms were reviewed by a blinded experienced imager for quantification of RV function (sinus and infundibular RV fractional area change) as well as for regional conduit site wall dysfunction (normal or abnormal, including hypokinesia, akinesia, or dyskinesia). Wilcoxon rank-sum tests were used to assess differences in RV infundibular and RV sinus ejection fraction and the Fisher exact test was used to assess differences in regional wall dysfunction. Results Twenty-two patients met inclusion criteria. Eight underwent traditional technique and 14 underwent PT. Median infundibular RV fractional area change was 49% and 37% (P = .02) and sinus RV fractional area change was 50% and 41% for PT and traditional technique (P = .007) respectively. Similarly qualitative regional RV wall function was better preserved in PT (P = .002). Conclusions The PT for RV to pulmonary artery conduit in Norwood operation results in better preservation of early RV global and regional systolic function. Whether or not this benefit translates to improved clinical outcome still needs to be studied.

Human parainfluenza virus type 3 (HPIV3) is a common cause of upper and lower respiratory tract illness in infants and young children. Live-attenuated cold-adapted HPIV3 vaccines have been evaluated in infants but a suitable interval for administration of a second dose of vaccine has not been defined.HPIV3-seronegative children between the ages of 6 and 36 months were randomized 2:1 in a blinded study to receive two doses of 10⁵ TCID₅₀ (50% tissue culture infectious dose) of live-attenuated, recombinant cold-passaged human PIV3 vaccine (rHPIV3cp45) or placebo 6 months apart. Serum antibody levels were assessed prior to and approximately 4-6 weeks after each dose. Vaccine virus infectivity, defined as detection of vaccine-HPIV3 in nasal wash and/or a≥4-fold rise in serum antibody titer, and reactogenicity were assessed on days 3, 7, and 14 following immunization.Forty HPIV3-seronegative children (median age 13 months; range 6-35 months) were enrolled; 27 (68%) received vaccine and 13 (32%) received placebo. Infectivity was detected in 25 (96%) of 26 evaluable vaccinees following doses 1 and 9 of 26 subject (35%) following dose 2. Among those who shed virus, the median duration of viral shedding was 12 days (range 6-15 days) after dose 1 and 6 days (range 3-8 days) after dose 2, with a mean peak log₁₀ viral titer of 3.4 PFU/mL (SD: 1.0) after dose 1 compared to 1.5 PFU/mL (SD: 0.92) after dose 2. Overall, reactogenicity was mild, with no difference in rates of fever and upper respiratory infection symptoms between vaccine and placebo groups.rHPIV3cp45 was immunogenic and well-tolerated in seronegative young children. A second dose administered 6 months after the initial dose was restricted in those previously infected with vaccine virus; however, the second dose boosted antibody responses and induced antibody responses in two previously uninfected children.

Objective The study objective was to develop a risk model incorporating diagnostic information to adjust for case-mix severity during routine monitoring of outcomes for pediatric cardiac surgery. Methods Data from the Central Cardiac Audit Database for all pediatric cardiac surgery procedures performed in the United Kingdom between 2000 and 2010 were included: 70% for model development and 30% for validation. Units of analysis were 30-day episodes after the first surgical procedure. We used logistic regression for 30-day mortality. Risk factors considered included procedural information based on Central Cardiac Audit Database "specific procedures," diagnostic information defined by 24 "primary" cardiac diagnoses and "univentricular" status, and other patient characteristics. Results Of the 27,140 30-day episodes in the development set, 25,613 were survivals, 834 were deaths, and 693 were of unknown status (mortality, 3.2%). The risk model includes procedure, cardiac diagnosis, univentricular status, age band (neonate, infant, child), continuous age, continuous weight, presence of non–Down syndrome comorbidity, bypass, and year of operation 2007 or later (because of decreasing mortality). A risk score was calculated for 95% of cases in the validation set (weight missing in 5%). The model discriminated well; the C-index for validation set was 0.77 (0.81 for post-2007 data). Removal of all but procedural information gave a reduced C-index of 0.72. The model performed well across the spectrum of predicted risk, but there was evidence of underestimation of mortality risk in neonates undergoing operation from 2007. Conclusions The risk model performs well. Diagnostic information added useful discriminatory power. A future application is risk adjustment during routine monitoring of outcomes in the United Kingdom to assist quality assurance.

As mortality after major cardiac surgery in early childhood falls, it becomes clearer that there is a high prevalence of ‘non-cardiac’ problems in survivors. Patient support groups for cardiac children have long lobbied for better access to general paediatric expertise and upcoming organizational changes underwrite this. Motor and cognitive deficits as well as emotional and behavioural difficulties may need addressing; all impact the child's quality of life. Participation in exercise-based activities and quality of life correlate poorly with disease severity, except at the worst end of the spectrum of heart disease. Cardiac function as measured objectively poorly predicts children's activity in daily life and some children are actively limited by personal habit or family concern, which is often inappropriate. Enough is now known about the prevalence of problems that survivors of childhood cardiac surgery experience in the education system that support may be justified, even when the original cardiac condition is no longer an ongoing problem.

Summary Background Assessment of the effect of fetal diagnosis on the prevalence of congenital heart disease at term requires national ascertainment because referral patterns are not rigorously structured. Methods Between 1993 and 1995, all 17 paediatric cardiac centres in the UK submitted to a database lists of all fetuses diagnosed, and all infants needing surgery or interventional catheterisation or dying in the first year of life because of structural heart disease; details included the postal area of residence. Findings There were 4799 affected pregnancies, 4165 babies born alive, 1124 fetal diagnoses, and 567 terminations of pregnancy because the fetus had structural heart disease. Thus, a fetal diagnosis was made in 23·4% of affected pregnancies (11·7% of all affected livebirths) with geographical variability in diagnostic rates. Interpretation Fetal cardiac screening has an effect on the prevalence and types of congenital heart disease seen at term because many affected pregnancies are terminated. If detection rates of affected fetuses rose nationally to those seen in the 15 postal areas where detection rates were significantly higher than the national average in 1993–95, we would expect about 218 fewer affected individuals to be born annually.

Objectives. This study attempted to assess whether coronary risk factors are associated with endothelial dysfunction in the systemic arteries of asymptomatic men and women. Background. Endothelial dysfunction is present in adults with established atherosclerosis. It is not known whether risk factors interact to produce endothelial dysfunction in clinically well subjects early in the natural history. Methods. Using high resolution ultrasound, we measured arterial diameter at rest, after reactive hyperemia (with increased flow causing endothelium-dependent dilation) and after sublingual nitroglycerin (an endothelium-independent dilator). Arterial responses were studied noninvasively in 500 clinically well, nonhypertensive subjects (252 men, 248 women; mean [± SD] age 36 ± 15 years, range 5 to 73), including 179 current and former smokers. The superficial femoral artery was studied in 46 subjects and the brachial artery in 454. Results. Flow-mediated dilation ranged from −1% to +17%. All arteries dilated in response to administration of nitroglycerin (17 ± 6%), suggesting an abnormality of endothelial function in subjects with impaired flow-mediated dilation. On univariate analysis, reduced flow-mediated dilation was significantly related to hypercholesterolemia, cigarette smoking, higher blood pressure, male gender, older age, family history of premature vascular disease and larger vessel size (p < 0.01). By multiple stepwise regression analysis, reduced flow-mediated dilation was independently associated with cigarette smoking, older age, male gender and larger vessel size (p < 0.0115) bat not with total cholesterol level, blood pressure or family history. A composite risk factor score was independently related to flow-mediated dilation (r = −0.30, p < 0.0001), suggesting risk factor interaction. Conclusions. Loss of endothelium-dependent dilation in the systemic arteries occurs in the preclinical phase of vascular disease and is associated with interaction of the same risk factors known to predispose to atherosclerosis and its complications in later life.

The data available on 111 patients with congenitally corrected transposition and 2 adequate ventricles managed over the 20-year period to 1988 were reviewed retrospectively. The ages of survivors ranged from 1 to 58 years (median 20) and all but 10 had additional anatomic abnormalities. Tricuspid valve abnormalities were more prevalent in patients symptomatic with heart failure (26 of 43 patients) than those whose main problem was cyanosis (11 of 52 patients); all dysplastic or Ebstein valves were at least moderately incompetent. Intracardiac repair of the lesion was attempted in 51 patients with 11 early deaths; in multivariate models, the risk factors for early death or a bad early outcome or poor result 6 months later related to poor preoperative symptomatic status (especially from heart failure), impaired right ventricular function, heart block and younger age at surgery. Patients with more than mild preoperative trkuspid regurgitation whose valves were not replaced did very poorly. Thus, patients symptomatic from heart failure should probably be repaired early in the natural history of the disease, before the systemic right ventricles dilate. By contrast, the course of patients who were predominantly cyanosed was more stable in early childhood and their surgical outcome was less compromised by poor preoperative symptomatic status; their intracardiac repair can probably be delayed until symptoms become unacceptable.

A 10-week-old infant with left atrial isomerism and a primum atrioventricular septal defect presented with life-threatening episodes of collapse. They proved due to paroxysmal pulmonary hypertension, although her pulmonary artery pressure was virtually normal between attacks. The pulmonary hypertensive crises persisted early but resolved late after surgical correction. Labile pulmonary vascular resistance may prove a problem preoperatively if the ventricular septum is intact.

The advantages and limitations of cardioplegia as a mode of myocardial preservation in the pediatric cardiac surgical context are investigated. Review of early mortality related to ischemic time demonstrated no difference in overall mortality in consecutive series each of 200 patients, the first protected by reperfusion between intermittent periods of aortic cross-clamping and the second protected by cardioplegia. There was a tendency to accept longer ischemic time with cardioplegia (p

Between 1971 and 1982, 249 patients received right heart extracardiac conduits. The 173 patients who survived 30 days were reviewed retrospectively; 72 had antibiotic-sterilized aortic homografts, 97 had xenografts of various types, and four had valveless tubes. Reoperation for conduit obstruction was required as early as 13 months after the original operation, but actuarial analysis showed no differences in overall performance of homograft and heterograft conduit groups with respect to late death or survival free of conduit obstruction. More important risk factors for late death or the need for reoperation were the severity of the underlying cardiac lesions and the influence of early postoperative complications. When analyzed statistically, the performance of conduits bearing homografts was disappointing, influenced sometimes by complications in the Dacron extension tubes. Repairs dispensing with conduits entirely should be evaluated.

To understand better the contribution of a right atrium in a valveless atriopulmonary connection, we performed some basic hydrodynamic studies. Pulsation of a valveless chamber in a simple continuous flow circuit was found to generate turbulence and thereby to increase resistance to net forward flow. Visualization of flow through cavities and around corners and measurements of energy losses across nonpulsatile cavities, corners, and stenoses indicated the importance of streamlining. These studies suggested ways in which hydrodynamic designs of the Fontan circulation might be improved. In parallel with these in vitro studies, we have developed a modified approach to Fontan reconstruction that entails exclusion of most or all of the right atrium (total cavopulmonary connection). The operation consists of three parts: (1) end-to-side anastomosis of the superior vena cava to the undivided right pulmonary artery; (2) construction of a composite intraatrial tunnel with the use of the posterior wall of the right atrium; and (3) use of a prosthetic patch to channel the inferior vena cava to the enlarged orifice of the transected superior vena cava that is anastomosed to the main pulmonary artery. The operation was performed in 20 patients between March 1987 and March 1988. The diagnoses were double-inlet ventricle (11 patients), hypoplastic systemic or pulmonary ventricle (seven patients), and absent right atrioventricular connection (two patients). There were two early deaths and one late death. None of the deaths was related to the actual procedure but rather to increased pulmonary vascular resistance (two patients) or systemic ventricular failure (one patient). Total cavopulmonary connections have the following advantages: (1) They are technically simple and reproducible in any atrioventricular arrangement and are away from the atrioventricular node; (2) most of the right atrial chamber remains at low pressure, which reduces the risk of early or late arrhythmias; (3) reduction of turbulence prevents energy losses and should minimize the risk of atrial thrombosis; (4) postoperative cardiac catheterization performed in 10 patients confirmed these favorable flow patterns with minimal gradients throughout the connections. These encouraging early results support the continuing use of total cavopulmonary connection, at least for patients with a nonhypertrophied right atrium.

Percutaneous balloon dilation was attempted in three patients with mid baffle pulmonary venous pathway obstruction after the Mustard operation for transposition of the great arteries. The procedure was unsuccessful in a 3 year old boy. Evidence for relief of obstruction in the other two patients (7 and 14 years old, respectively) consisted of angiographic demonstration of improved caliber at the site of the pulmonary venous pathway narrowing, improvement in the Doppler spectral signal at this site from an “obstructed” to a “normal” pattern as well as symptomatic improvement. Balloon dilation was performed twice in one of these patients. The Doppler and symptomatic improvement were sustained in both patients at short-term follow-up (5 and 6 months, respectively). This technique may offer effective relief of pulmonary venous pathway obstruction in some patients with this complication of the Mustard operation.

In order to study the usefulness of incorporating a subpulmonary ventricular chamber (SPVC) in the Fontan circulation, we compared the hemodynamics of 18 patients who underwent an atriopulmonary connection with those of 17 patients with an atrioventricular connection. Early postoperatively, regardless of whether an SPVC was incorporated or not, the mean pulmonary artery pressure was not higher than the mean right atrial pressure in any of our patients. The stroke work of the right heart was at best zero, and pressure tracings showed an a wave in the pulmonary artery (right atrium-dependent circulation). If an additional gradient was interposed between the right atrium and pulmonary artery, the effective stroke work of the right heart might be negative and the work curve have a negative slope. This can occur irrespective of the use of an SPVC. In the long term, if it grows sufficiently, an SPVC can sometimes provide a right ventricle-dependent pulmonary circulation with a more normal hemodynamic pattern (mean right atrial pressure less than mean pulmonary artery pressure). We concluded that an SPVC should be used in Fontan’s circulation, provided that an obstruction-free atrioventricular connection can be established.