Circulating Spike Protein Detected in Post-COVID-19 mRNA Vaccine Myocarditis.

BACKGROUND: Cases of adolescents and young adults developing myocarditis after vaccination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-targeted mRNA vaccines have been reported globally, but the underlying immunoprofiles of these individuals have not been described in detail. METHODS: From January 2021 through February 2022, we prospectively collected blood from 16 patients who were hospitalized at Massachusetts General for Children or Boston Children's Hospital for myocarditis, presenting with chest pain with elevated cardiac troponin T after SARS-CoV-2 vaccination. We performed extensive antibody profiling, including tests for SARS-CoV-2-specific humoral responses and assessment for autoantibodies or antibodies against the human-relevant virome, SARS-CoV-2-specific T-cell analysis, and cytokine and SARS-CoV-2 antigen profiling. Results were compared with those from 45 healthy, asymptomatic, age-matched vaccinated control subjects. RESULTS: Extensive antibody profiling and T-cell responses in the individuals who developed postvaccine myocarditis were essentially indistinguishable from those of vaccinated control subjects, despite a modest increase in cytokine production. A notable finding was that markedly elevated levels of full-length spike protein (33.9±22.4 pg/mL), unbound by antibodies, were detected in the plasma of individuals with postvaccine myocarditis, whereas no free spike was detected in asymptomatic vaccinated control subjects (unpaired t test; P<0.0001). CONCLUSIONS: Immunoprofiling of vaccinated adolescents and young adults revealed that the mRNA vaccine-induced immune responses did not differ between individuals who developed myocarditis and individuals who did not. However, free spike antigen was detected in the blood of adolescents and young adults who developed post-mRNA vaccine myocarditis, advancing insight into its potential underlying cause.

Emergence of the natural history of Myhre syndrome: 47 patients evaluated in the Massachusetts General Hospital Myhre Syndrome Clinic (2016-2023).

Myhre syndrome is an increasingly diagnosed ultrarare condition caused by recurrent germline autosomal dominant de novo variants in SMAD4. Detailed multispecialty evaluations performed at the Massachusetts General Hospital (MGH) Myhre Syndrome Clinic (2016-2023) and by collaborating specialists have facilitated deep phenotyping, genotyping and natural history analysis. Of 47 patients (four previously reported), most (81%) patients returned to MGH at least once. For patients followed for at least 5 years, symptom progression was observed in all. 55% were female and 9% were older than 18 years at diagnosis. Pathogenic variants in SMAD4 involved protein residues p.Ile500Val (49%), p.Ile500Thr (11%), p.Ile500Leu (2%), and p.Arg496Cys (38%). Individuals with the SMAD4 variant p.Arg496Cys were less likely to have hearing loss, growth restriction, and aortic hypoplasia than the other variant groups. Those with the p.Ile500Thr variant had moderate/severe aortic hypoplasia in three patients (60%), however, the small number (n = 5) prevented statistical comparison with the other variants. Two deaths reported in this cohort involved complex cardiovascular disease and airway stenosis, respectively. We provide a foundation for ongoing natural history studies and emphasize the need for evidence-based guidelines in anticipation of disease-specific therapies.

The youngest pair of siblings with Mucopolysaccharidosis type IVA to receive enzyme replacement therapy to date: A case report.

Mucopolysaccharidosis type IVA (OMIM 253000) is an autosomal recessive disorder caused by defective activity of the N-acetylgalactosamine 6-sulfatase (GALNS) enzyme. In 2014, enzyme replacement therapy (ERT) using recombinant human GALNS became available for affected patients. There is a limited number of studies to date that have explored the effect of ERT in infancy and there is also a lack of data assessing the effect of ERT in systems other than the skeletal. Here, we report on the effect of ERT in the youngest pair of siblings treated to date: Patient A, currently 4 years old, who started treatment at the age of 5 months; and Patient B, currently 3 years old, who started treatment at 58 days of life. Moreover, we investigate the effect of early ERT on the cardiovascular system. Our results show that, even when ERT is started before 2 months of age, it cannot fully prevent disease progression. As for the effect of ERT on the cardiovascular system, our preliminary results suggest that early treatment might play a role in preserving a normal left ventricular mass index in affected patients at least up to 1 year, but further observation over time will be required. Overall, this report shows that early diagnosis remains crucial and that prompt initiation of ERT has limited effect in slowing progression of the skeletal phenotype, thus confirming the need for new therapeutic approaches that target the skeletal system in affected patients.

Point-of-Care Ultrasound in Sternal Notch Confirms Depth of Endotracheal Tube in Children.

OBJECTIVES: To determine if a saline-filled cuff seen at the suprasternal notch on ultrasound corresponds to correct endotracheal tube depth on a chest radiograph (tip at/below clavicle AND ≥ 1 cm above carina). DESIGN: Prospective observational study. SETTING: Tertiary Care Pediatric hospital. PATIENTS: Patients between the ages of 0-18 years requiring nonemergent cardiac catheterizations and endotracheal intubation with a cuffed endotracheal tube were included in the study. Children with anticipated or known difficult airways were excluded. INTERVENTIONS: Ultrasound evaluation of the neck following saline inflation of the endotracheal tube cuff. MEASUREMENTS AND MAIN RESULTS: Ultrasonography of the patient's neck was performed following intubation by a pediatric anesthesiologist. A linear probe was used in transverse axis to identify the saline-filled cuff starting at the suprasternal notch and moving cephalad. A cine-fluoroscopic image, similar to a chest radiograph, was obtained to ascertain the endotracheal tube depth after the cuff was identified sonographically. Endotracheal tube cuffs seen on ultrasound at the suprasternal notch were compared with the endotracheal tube depth on the cine-fluoroscopic image. A total of 75 children were enrolled in the study. The endotracheal tube was seen sonographically at the suprasternal notch in 70 patients of which 60 had complete data (an adequate chest radiograph available for review). Patient ages ranged from 2 months to 18 years with a median age of 4 years. The median endotracheal tube tip to carina distance was 2.4 cm (interquartile range, 1.75-3.3 cm.) The endotracheal tube tip to carina distance was greater than or equal to 1 cm in 57 out of the 60 patients. Endotracheal tube cuff at the suprasternal notch on ultrasound corresponded with correct endotracheal tube depth on chest radiograph with an accuracy of 95% (CI, 86-98%). CONCLUSIONS: Visualization of the cuff at the suprasternal notch by ultrasound demonstrates potential as a means of confirming correct depth of the endotracheal tube following endotracheal intubation.

Investigational lymphatic imaging at the bedside in a pediatric postoperative chylothorax patient.

Chylothorax is a rare but serious complication in children who undergo heart surgery. Its pathogenesis is poorly understood, and invasive surgical treatments are considered only after conservative management fails. Current diagnostic imaging techniques, which could aid decision making for earlier surgical intervention, are difficult to apply. Herein, we deployed near-infrared fluorescence (NIRF) lymphatic imaging to allow the visualization of abnormal lymphatic drainage in an infant with postoperative chylothorax to guide the choice of surgical management. A 5-week-old male infant, who developed chylothoraces after undergoing Norwood surgery for hypoplastic left heart syndrome, was intradermally administered trace doses of indocyanine green in both feet and the left hand. NIRF imaging was then performed at the bedside to visualize lymphatic drainage patterns. Imaging results indicated impeded lymphatic drainage from the feet toward the trunk with no fluorescence in the chest indicating no leakage of peripheral lymph at the thoracic duct. Instead, lymph drainage occurred from the axilla directly into the pleural cavity. As a result of imaging, left pleurodesis was performed to stop the pleural effusion with the result of temporary decrease of left chest tube drainage. Although additional studies are required to understand normal and abnormal lymphatic drainage patterns in infants, we showed the potential of using NIRF lymphatic imaging at the bedside to visualize the lymphatic drainage pathway to guide therapy. Timely management of chylothorax may be improved by using NIRF imaging to understand lymphatic drainage pathways.

In Utero Exposure to Maternal SARS-CoV-2 Infection Is Associated With Higher Left Ventricular Mass in Toddlers.

The intrauterine environment plays a critical role in shaping chronic disease risk over the life course. We prospectively evaluated cardiometabolic outcomes in toddlers born to mothers with versus without prenatal severe acute respiratory syndrome coronavirus 2 infection. Children with in utero severe acute respiratory syndrome coronavirus 2 exposure had higher left ventricular mass in association with altered maternal immunologic indices.

Spontaneous closure of patent ductus arteriosus in preterm babies after failed attempts at transcatheter device closure.

Transcatheter closure of patent ductus arteriosus (PDA) for preterm infants is increasingly performed after the Food and Drug Administration approval of the Amplatzer Piccolo Occluder device (Abbott Inc., Abbott Park, IL, USA) in the United States. We report three babies in whom transcatheter closure of PDA was unsuccessful; however, the PDA closed spontaneously in 1-5 days after the transcatheter attempt. The PDA remained closed during follow-up at 3 weeks, 10 weeks, and 17 months, respectively. Mechanical stimulation of the PDA by the wire during attempted device closure likely induced the PDA closure. Further studies are needed to evaluate whether this is a useful alternative therapy in this patient population.

Computed tomography scan measurement of abdominal wall thickness for application of near-infrared spectroscopy probes to monitor regional oxygen saturation index of gastrointestinal and renal circulations in children.

OBJECTIVES: To measure abdominal wall thickness to determine the depth at which the renal vascular bed and mesenteric vascular bed are located, and to determine the appropriate site for placement of near-infrared spectroscopy probes for accurate monitoring regional oxygen saturation index in children. DESIGN: Abdominal computerized tomography scans in children were used to measure the abdominal wall thickness and to ascertain the location of kidneys. SETTING: Tertiary care children's hospital. SUBJECTS: Children 0-18 yrs of age; n = 38. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main mass of the kidneys is located between vertebral levels T12 and L2 on both sides. The left kidney is located about a half-vertebral length higher than the right kidney. Posterior abdominal wall thickness ranged from 6.6 to 115.8 mm (median, 22.1 mm). Posterolateral abdominal wall thickness ranged from 6.7 to 114.5 mm (median, 19.6 mm). Anterior abdominal wall thickness in the supraumbilical level ranged from 3.5 to 62.9 mm (median, 16.0 mm). All abdominal wall thicknesses correlated better with weight of the subjects than their age. CONCLUSION: Abdominal wall thickness potentially exceeds the sampling depth of currently used near-infrared spectroscopy probes above a certain body size. Application of current near-infrared spectroscopy probes and design of future probes should consider patient size variations in the pediatric population.

Multimodality lymphatic imaging of postoperative chylothorax in an infant with Noonan syndrome: a case report.

BACKGROUND: Chylothorax is a rare complication of pediatric cardiac operations that occurs more frequently in children with Noonan syndrome, a genetic disorder associated with cardiac defects and lymphatic anomalies. CASE PRESENTATION: We report a case of postoperative chylothorax in a 6-month-old infant with Noonan syndrome where multimodality lymphatic imaging guided management was followed. Drainage patterns of the lymphatic capillaries in the lower and upper extremities were visualized during near-infrared fluorescence lymphatic imaging (NIRFLI). Dynamic magnetic resonance lymphangiography (MRL) further identified the site of leakage in the thoracic duct and subsequently guided surgical intervention. CONCLUSIONS: Application of multimodality imaging allows for greater individualization of treatment and should be considered in patients with complex cases such as those with syndromes associated with a higher incidence of chylothorax. IRB Number: HSC-MS-13-0754, December 10, 2013.

Effect of Intravenous Phenobarbital on Left Ventricular Myocardial Contractility Determined by Echocardiography in Children.

INTRODUCTION: Animal studies and rare human studies have suggested a negative effect of barbiturates on cardiac function. Although intravenous (IV) phenobarbital is used routinely in children in the clinical setting, studies in children are lacking. We performed a study to evaluate effect of IV phenobarbital loading on myocardial systolic function of children. METHODS: In a prospective pilot study in children without congenital heart defects, the effect of IV phenobarbital was evaluated on the left ventricular systolic function measured by ejection fraction (EF) by Simpson's method via an echocardiogram. Any child less than 18 years of age who received IV loading dose of at least 20 mg/kg of phenobarbital given as an infusion over 20 - 30 minutes for various medical indications was eligible to take part in the study. Three measurements of EF by an echocardiogram were made: before loading dose, 30 minutes after completion of the loading dose, and prior to the first maintenance dose. Relevant clinical data were recorded, including vital signs, immediately prior to each echocardiogram. Change of function as measured by EF over time was analyzed using linear mixed modeling methods. For this study, significant change in blood pressure was defined as a drop of at least 20 mmHg in systolic blood pressure. RESULTS: Ten children (70% female, age range two days to 8.2 years) were enrolled. Three had hypotension with a drop of systolic blood pressure greater than 20 mmHg from baseline. On examining the trajectory of EF on each individual graphically, the left ventricular EF tended to fall immediately following phenobarbital therapy and return to baseline on re-evaluation. These trajectories were statistically significant for EF. CONCLUSIONS: Phenobarbital had a direct and transient depressant effect on systolic function of the myocardium in one third of the cases. The depression in EF appeared to be transient with return to baseline in less than 24 hours. We recommend close monitoring with anticipation of decreased function in children when using IV phenobarbital.

Comparison of skin dose measurement using nanoDot® dosimeter and machine readings of radiation dose during cardiac catheterization in children.

OBJECTIVES: Direct measurement of skin dose of radiation for children using optically stimulated luminescence (OSL) technology using nanoDot® (Landauer, Glenwood, IL, USA). BACKGROUND: Radiation dose is estimated as cumulative air kerma (AK) and dosearea product based on standards established for adult size patients. Body size of pediatric patients who undergo cardiac catheterization for congenital heart disease vary widely from newborn to adolescence. Direct, skindose measurement applying OSL technology may eliminate errors in the estimate. MATERIALS AND METHODS: The nanoDot® (1 cm × 1 cm × flat plastic cassette) is applied to patient's skin using adhesive tape during cardiac catheterization and radiation skin doses were read within 24 hrs. nanoDot® values were compared to the currently available cumulative AK values estimated and displayed on fluoroscopy monitor. RESULTS: A total of 12 children were studied, aged 4 months to 18 years (median 1.1 years) and weight range 5.3-86 kg (median 8.4 kg). nanoDot® readings ranged from 2.58 mGy to 424.8 mGy (median 84.1 mGy). Cumulative AK ranged from 16.2 mGy to 571.2 mGy (median 171.1 mGy). Linear correlation was noted between nanoDot® values and AK values (R2 = 0.88, R = 0.94). nanoDot® readings were approximately 65% of the estimated cumulative AK estimated using the International Electrotechnical Commission standards. CONCLUSIONS: Application of OSL technology using nanoDot® provides an alternative to directly measure fluoroscopic skin dose in children during cardiac catheterization. Our data show that the actual skin dose for children is approximately one-third lower than the AK estimated using international standards for adult size patients.

Healthy Adolescent with a Mycotic Aortic Aneurysm from Community-Acquired Methicillin-Resistant Staphylococcus aureus.

Mycotic aneurysm after bacteremia is a rare diagnosis in children and adolescents. We report the case of a previously healthy adolescent who presented with chest pain and fever and who developed a mycotic aneurysm of the aorta after contracting community-acquired, methicillin-resistant Staphylococcus aureus. Early recognition of widening of the patient's superior mediastinum, noted during a comparison of the patient's initial and follow-up chest radiographs, prompted computed tomographic angiography of the chest and led to a timely diagnosis, rapid surgical intervention, and a good clinical outcome. To our knowledge, this is the first reported case of mycotic aortic aneurysm from community-acquired methicillin-resistant S. aureus in a healthy adolescent who had no predisposing cardiac or aortic anomalies.

Anomalous Origin of Coronary Artery From Main Pulmonary Artery in Hypoplastic Left Heart Syndrome.

We report a case of anomalous origin of the left anterior descending coronary artery (LAD) from the main pulmonary artery in a child with hypoplastic left heart syndrome (mitral atresia/aortic atresia). Mechanical circulatory support was necessary because of the inability to wean from cardiopulmonary bypass after the Norwood procedure. The patient died at 4 months of age having continued depressed right ventricular function. The diagnosis was made during a catheterization performed 6 weeks after surgery because of concern for stenosis of Blalock-Taussig shunt. We believe his prolonged postoperative recovery and eventual demise can partially be attributed to lack of cardioplegia to the anomalous LAD territory during surgery.

Unusual presentation of unroofed coronary sinus with cyanosis after ventricular septal defect closure.

Cyanosis after surgical closure of ventricular and/or atrial septal defect is very unusual. We report a case of unroofed coronary sinus in a six-month-old boy who developed cyanosis after surgical closure of ventricular and atrial septal defects. Clinical presentation, diagnosis, and management are discussed.

Anomalous origin of left coronary artery from pulmonary artery - Duped by 2D; saved by color Doppler: Echocardiographic lesson from two cases.

Echocardiography is an important first-line investigation for detection of anomalous origin of a coronary artery from the pulmonary artery (ALCAPA). We report two cases of ALCAPA that illustrate the importance of systematic performance of the echocardiogram, mindful of technical artifacts that may mislead the echocardiographer color Doppler imaging in diagnosis of this condition.

Conivaptan therapy in an infant with severe hyponatremia and congestive heart failure.

Conivaptan is a nonspecific arginine vasopressin receptor antagonist that has been used as therapy in adults who have hypervolemic hyponatremia due to congestive heart failure. Its use in children with congestive heart failure has not been reported. We describe the use of conivaptan in a 4-month-old infant girl with severe hypervolemic hyponatremia and heart failure. A therapeutic weight-based dose was extrapolated from the adult dose. Conivaptan therapy was administered for 48 hours, after which the patient recovered from her hyponatremia without untoward effects. Arginine vasopressin receptor antagonists such as conivaptan may be useful as therapy for hyponatremia associated with heart failure. Further studies are required before conivaptan can be recommended for routine use in children.