Mind the Gap! Working Toward Gender Equity in Pediatric and Congenital Heart Disease: Present and Future.

Evidence from medicine and other fields has shown that gender diversity results in better decision making and outcomes. The incoming workforce of congenital heart specialists (especially in pediatric cardiology) appears to be more gender balanced, but past studies have shown many inequities. Gender-associated differences in leadership positions, opportunities presented for academic advancement, and recognition for academic contributions to the field persist. In addition, compensation packages remain disparate if evaluated based on gender with equivalent experience and expertise. This review explores these inequities and has suggested individual and institutional changes that could be made to recruit and retain women, monitor the climate of the institution, and identify and eliminate bias in areas like salary and promotions.

Design and implementation of multicenter pediatric and congenital studies with cardiovascular magnetic resonance: Big data in smaller bodies.

Cardiovascular magnetic resonance (CMR) has become the reference standard for quantitative and qualitative assessment of ventricular function, blood flow, and myocardial tissue characterization. There is a preponderance of large CMR studies and registries in adults; However, similarly powered studies are lacking for the pediatric and congenital heart disease (PCHD) population. To date, most CMR studies in children are limited to small single or multicenter studies, thereby limiting the conclusions that can be drawn. Within the PCHD CMR community, a collaborative effort has been successfully employed to recognize knowledge gaps with the aim to embolden the development and initiation of high-quality, large-scale multicenter research. In this publication, we highlight the underlying challenges and provide a practical guide toward the development of larger, multicenter initiatives focusing on PCHD populations, which can serve as a model for future multicenter efforts.

Application of Electrical Stimulation to Enhance Axon Regeneration Following Peripheral Nerve Injury.

Enhancing axon regeneration is a major focus of peripheral nerve injury research. Although peripheral axons possess a limited ability to regenerate, their functional recovery is very poor. Various activity-based therapies like exercise, optical stimulation, and electrical stimulation as well as pharmacologic treatments can enhance spontaneous axon regeneration. In this protocol, we use a custom-built cuff to electrically stimulate the whole sciatic nerve for an hour prior to transection and repair. We used a Thy-1-YFP-H mouse to visualize regenerating axon profiles. We compared the regeneration of axons from nerves that were electrically stimulated to nerves that were not stimulated (untreated). Electrically stimulated nerves had longer axon growth than the untreated nerves. We detail how variations of this method can be used to measure acute axon growth.

The Ganesh-Grewal cystitome maker - A step in standardizing cataract surgery.

A well-centered, adequately sized continuous curvilinear capsulorhexis (CCC) is a prerequisite for successful cataract surgery. A perfect capsulorhexis ensures safe and effective performance of various steps of surgery as well as a correctly positioned intraocular lens (IOL) with optimal rotational stability. Ganesh and Grewal (GG) cystitome maker is a step toward standardizing the creation of a cystitome to reduce variations and complications associated with the crucial step of CCC in cataract surgery. We conducted a study to measure the repeatability and precision of cystitomes made by the GG cystitome maker versus those made manually with a needle holder. The results showed that the cystitomes made with GG cystitome maker had a lesser degree of variation. This indicates a more repeatable cystitome, which will inadvertently help in reducing the error caused by the instrument in making a good CCC during cataract surgery.

Genetic mapping identified three hotspot genomic regions and candidate genes controlling heat tolerance-related traits in groundnut.

Groundnut productivity and quality have been impeded by rising temperatures in semi-arid environments. Hence, understanding the effects and molecular mechanisms of heat stress tolerance will aid in tackling yield losses. In this context, a recombinant inbred line (RIL) population was developed and phenotyped for eight seasons at three locations for agronomic, phenological, and physiological traits under heat stress. A genetic map was constructed using genotyping-by-sequencing with 478 single-nucleotide polymorphism (SNP) loci spanning a map distance of 1,961.39 cM. Quantitative trait locus (QTL) analysis using phenotypic and genotypic data identified 45 major main-effect QTLs for 21 traits. Intriguingly, three QTL clusters (Cluster-1-Ah03, Cluster-2-Ah12, and Cluster-3-Ah20) harbor more than half of the major QTLs (30/45, 66.6%) for various heat tolerant traits, explaining 10.4%-38.6%, 10.6%-44.6%, and 10.1%-49.5% of phenotypic variance, respectively. Furthermore, important candidate genes encoding DHHC-type zinc finger family protein (arahy.J0Y6Y5), peptide transporter 1 (arahy.8ZMT0C), pentatricopeptide repeat-containing protein (arahy.4A4JE9), Ulp1 protease family (arahy.X568GS), Kelch repeat F-box protein (arahy.I7X4PC), FRIGIDA-like protein (arahy.0C3V8Z), and post-illumination chlorophyll fluorescence increase (arahy.92ZGJC) were the underlying three QTL clusters. The putative functions of these genes suggested their involvement in seed development, regulating plant architecture, yield, genesis and growth of plants, flowering time regulation, and photosynthesis. Our results could provide a platform for further fine mapping, gene discovery, and developing markers for genomics-assisted breeding to develop heat-tolerant groundnut varieties.

Comparative Evaluation of Effect of Micro-Osteoperforation and Mechanical Vibration on Rate of Orthodontic Tooth Movement in Young Adults With Bimaxillary Protrusion.

AIM: To evaluate and compare the rate of orthodontic tooth movement and root resorption by micro-osteoperforation (MOP) and mechanical vibration in young adults with bimaxillary protrusion. METHOD: Twenty patients having class I bimaxillary protrusion who required all first premolar extraction were allocated into two groups MOP (Group A) and mechanical vibration (Group B), with a 1:1 allocation ratio. After leveling alignment MOP was performed on either side of the arch, and vibration was applied on the contralateral side 20 mins per day. Canines were retracted with nickel-titanium coil springs, and Alginate impressions were taken every four weeks till 4 months. RESULT: The mean rate of retraction of canines of Group A was more than Group B. There was a statistically significant difference between Group A and Group B. (p=0.0120) Conclusion: The mean rate of retraction of canines treated by MOP was 1.15 mm per 4 weeks, and by mechanical vibration, 0.8mm per 4 weeks.

Patterns and Trends of Facial Fractures at a Tertiary Care Trauma Center in India - A 13 years Retrospective Study.

Study Design: Retrospective study. Objective: The purpose of this study was to retrospectively analyze the prevalence, pattern, diagnosis, and treatment of the facial fractures falling under ambit of facial plastic surgery in a multi-specialty hospital at India from the year 2006-2019. Methods: This retrospective study analyzed 1508 patients, having orbital fractures (from 2006 to 2019) for demographic data, cause of trauma, type of fracture, and the treatment given. The data were compiled in excel and analyzed by using SPSS version 21.0. Results: Out of these 1508 patient (1127 (74.73%)-males and 381 (25.27%)-females), the etiology of injuries was Road traffic accident (RTA) (49.20%), assault (26.52%), and sports injuries (11.47%). The most common fracture pattern was Isolated Orbit and/or Orbital Floor fracture in 451 patients (32.08%), followed by Mid-facial fractures (21.93%). Also, 105 patients (6.96%) experienced ocular/retinal trauma along with other fractures. Conclusions: Orbit, peri-ocular, and mid-face trauma comprised a large position of this study. It requires a great deal of expertise to treat such complex trauma, which is not covered in one specialty alone. Hence, a holistic approach of craniofacial fracture management, rather than limiting these skills to water-tight craniofacial compartments becomes necessary. The study highlights the critical need of multidisciplinary approach for predictable and successful management of such complex cases.

Biodeterioration of polyethylene by jellyfish nematocyst protein.

Plastic pollution is one of the major global problems existing now-a-days and has become a cause of serious concern in coastal and marine ecosystems. Increased accumulation of plastics in the aquatic environment by anthropogenic sources results the alteration of the aquatic ecosystem and its functioning. Several variables have an impact on biodegradation, ranging from microbe species to polymer type, physicochemical qualities, and environmental circumstances. The present study was attempted to investigate polyethylene degradation ability of nematocyst protein extracted from the lyophilized nematocyst samples using three different mediums such as distilled water, Phosphate buffered saline (PBS), and seawater. The biodeteriorization potential of nematocyst protein and its interaction with the polyethylene was studied using ATR-IR, phase contrast bright-dark field microscope, and scanning electron microscopic studies. The results uncover the biodeteriorization of polyethylene by jellyfish nematocyst protein without any external physicochemical process and provide evidence for further research.

Cardiovascular magnetic resonance for evaluation of cardiac involvement in COVID-19: recommendations by the Society for Cardiovascular Magnetic Resonance.

Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic that has affected nearly 600 million people to date across the world. While COVID-19 is primarily a respiratory illness, cardiac injury is also known to occur. Cardiovascular magnetic resonance (CMR) imaging is uniquely capable of characterizing myocardial tissue properties in-vivo, enabling insights into the pattern and degree of cardiac injury. The reported prevalence of myocardial involvement identified by CMR in the context of COVID-19 infection among previously hospitalized patients ranges from 26 to 60%. Variations in the reported prevalence of myocardial involvement may result from differing patient populations (e.g. differences in severity of illness) and the varying intervals between acute infection and CMR evaluation. Standardized methodologies in image acquisition, analysis, interpretation, and reporting of CMR abnormalities across would likely improve concordance between studies. This consensus document by the Society for Cardiovascular Magnetic Resonance (SCMR) provides recommendations on CMR imaging and reporting metrics towards the goal of improved standardization and uniform data acquisition and analytic approaches when performing CMR in patients with COVID-19 infection.

Assessment of homozygosity in transgenic plants using selectable markers.

Production of homozygous transgenic plants is a prerequisite for the phenotypic analysis and/or for the commercial release of transgenic plants for cultivation. Here we present a simple protocol for the selection of homozygous transgenics using antibiotics as a selectable marker. The protocol has been used to select homozygous rice transgenic plants using hygromycin antibiotic. However, the described protocol can be used for selction of homozygous in any transgenic plants using a appropriate selectable marker. For complete details on the use and execution of this protocol, please refer to Passricha et al. (2016).1.

COVID-19 Positive Versus Negative Complete Kawasaki Disease: A Study from the International Kawasaki Disease Registry.

To determine clinical differences for children with complete Kawasaki disease (KD) with and without evidence of preceding SARS-CoV-2 infection. From January 2020, contemporaneous patients with complete KD criteria were classified as either SARS-CoV-2 positive (KDCOVID+; confirmed household exposure, positive PCR and/or serology) or SARS-CoV-2 negative (KDCOVID-; negative testing and no exposure) and compared. Of 744 patients in the International Kawasaki Disease Registry, 52 were KDCOVID- and 61 were KDCOVID+. KDCOVID+ patients were older (median 5.5 vs. 3.7 years; p < 0.001), and all additionally met diagnostic criteria for multisystem inflammatory syndrome in children (MIS-C). They were more likely to have abdominal pain (60% vs. 35%; p = 0.008) and headache (38% vs. 10%; p < 0.001) and had significantly higher CRP, troponin, and BUN/creatinine, and lower hemoglobin, platelets, and lymphocytes. KDCOVID+ patients were more likely to have shock (41% vs. 6%; p < 0.001), ICU admission (62% vs. 10%; p < 0.001), lower left ventricular ejection fraction (mean lowest LVEF 53% vs. 60%; p < 0.001), and to have received inotropic support (60% vs. 10%; p < 0.001). Both groups received IVIG (2 doses in 22% vs. 18%; p = 0.63), but KDCOVID+ were more likely to have received steroids (85% vs. 35%; p < 0.001) and anakinra (60% vs. 10%; p = 0.002). KDCOVID- patients were more likely to have medium/large coronary artery aneurysms (CAA, 12% vs. 0%; p = 0.01). KDCOVID+ patients differ from KDCOVID-, have more severe disease, and greater evidence of myocardial involvement and cardiovascular dysfunction rather than CAA. These patients may be a distinct KD phenotype in the presence of a prevalent specific trigger.

Enhanced photocatalytic degradation of caffeine using Co-Zn/Al2O3 nanocomposite.

This work focuses on the synthesis and characterization of photocatalytic activity of Co-Zn/Al2O3 nanocomposite obtained by calcination of Co-loaded Zn/aluminum layered double hydroxide by wet impregnation method. The catalyst was characterized by X-ray diffraction (XRD), Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), BET and UV-DRS. The evaluation of catalytic activity was investigated for the degradation of emerging pharmaceutical pollutant caffeine in aqueous solutions under UV irradiation. The process parameters were optimized for the maximum removal of caffeine. A maximum caffeine removal of 92% was obtained with the optimal conditions at the catalytic dosage of 0.5 g/L, contact time of 50 min, initial concentration of 50 mg/L, and pH of 9.5. The batch experimental data coincide well with the pseudo first order kinetic model, the rate constant of 0.012 min-1, with the R2 value of 0.875-0.938. The regeneration study reveals that the catalyst has high stability and maximum removal efficiency. Hence, the synthesized nanocatalyst is considered a potential photo catalyst for removing the pharmaceutical pollutant caffeine from aqueous solutions.

Silver nanoparticles based spectroscopic sensing of eight metal ions in aqueous solutions.

Anthropogenic releases from different outlets of industry, municipal sewage and the road traffic can give rise to higher concentrations of heavy metals in food commodities which imposes a threat to human health and environment. A simple silver nanoparticle (Ag NPs) used for the sensing of heavy metal ions, Cd2+, Cu2+, Fe2+, Hg2+, Mn2+, Ni2+, Pb2+ and Zn2+ in aqueous solution is described qualitatively and quantitatively using spectroscopic tool. FE-SEM and TEM images confirmed that the particles are spherical in shape with an average diameter of 23.4 nm. Presence of heavy metal ions with Ag NPs gives, new peak at around 925, 898, 643, 665, 688, and 838 nm for Cd2+, Cu2+, Fe2+, Hg2+, Mn2+ and Zn2+ in addition to the peak found at 410 nm for Ag NPs. Further, the addition of Ni2+ and Pb2+ metal ion solution with Ag NPs increased the SPR band from 410 nm to 436 and 462 nm respectively. Citrate functionalized Ag NPs aggregate in solution in the presence of divalent metal ions by ions-template chelating process and are easily measurable changes in the UV-vis absorption spectrum of the particles. Further, studies also confirmed the interaction of Ag NPs with metal ions using FT-IR spectroscopy. The proposed method was found to be useful for simple UV-vis spectroscopic sensing of metal ions in aqueous solutions and real contaminated samples.

Angiogenesis is critical for the exercise-mediated enhancement of axon regeneration following peripheral nerve injury.

Enhancing axon regeneration is a major focus of nerve injury research, and the quality of the surgical nerve repair plays a large role in the aggregate success of nerve regeneration. Additionally, exercise is known to promote successful axon regeneration after surgical nerve repair. In this study, we asked how exercise-induced nerve regeneration is affected when a transected nerve is repaired with or without fibrin glue. Fibrin glue repaired nerves exhibited greater vasculature within the tissue bridge compared to nerves that were intrinsically repaired. Fibrin glue repaired nerves also exhibited more robust axon regeneration after exercise compared to nerves that were not repaired with fibrin glue. When angiogenesis of the tissue bridge was prevented, exercise was unable to enhance regeneration despite the presence of fibrin glue. These findings suggest that the biological properties of fibrin glue enhance angiogenesis within the repair site, and a vascularized bridge is required for enhanced axon elongation with exercise. The combination of fibrin glue repair and exercise resulted in notable differences in vascular growth, axon elongation, neuromuscular junction reinnervation, and functional recovery. Fibrin glue should be considered as an adjuvant for nerve repair to enhance the subsequent efficacy of activity- and physical therapy-based treatment interventions.

Association of Acute Anti-inflammatory Treatment With Medium-term Outcomes for Coronary Artery Aneurysms in Kawasaki Disease.

Background: The impact of adjunctive anti-inflammatory treatment on outcomes for patients with Kawasaki disease (KD) and coronary artery aneurysms (CAAs) is unknown. Methods: Using data from the International KD Registry in patients with ≥ medium CAA we evaluate associations of treatment with outcomes and major adverse cardiac events (MACE). Results: Medium or large CAA was present in 527 (32%) patients. All were treated with intravenous immunoglobulin (IVIG), 70% were male, and the median age was 1.3 years (interquartile range: 0.4-4.0 years). The most common acute therapies included single IVIG alone in 243 (46%), multiple IVIG in 100 (19%), multiple IVIG + corticosteroids in 75 (14%), and multiple IVIG + infliximab + corticosteroids in 44 (8%) patients. Patients who received therapy beyond single IVIG had a larger CA z-score at baseline (P < 0.001) and a higher rate of bilateral CAA (P < 0.001). Compared with IVIG alone, early adjunctive treatments (within 3 days of initial IVIG) were not associated with time to CAA regression or MACE, whereas later adjunctive therapy was associated with MACE and longer time to CAA regression. Patients receiving IVIG plus steroids vs IVIG alone had a trend towards shorter time to CAA regression and lower risk of MACE (P = 0.07). A larger CAA z-score at baseline was the strongest predictor of an increase in the CAA z-score over follow-up, lower likelihood of CAA regression, and higher risk of MACE. Conclusions: Persistence of CAA and MACE are more strongly associated with baseline severity CAA than with acute adjuvant anti-inflammatory therapy. Patients who received late adjunctive therapy are at higher risk for worse outcomes.

Contexte: L'incidence d'un traitement anti-inflammatoire d'appoint chez les patients atteints de la maladie de Kawasaki (MK) compliquée d'anévrismes coronariens est inconnue. Méthodologie: À partir de données provenant du registre international de la maladie de Kawasaki portant sur les patients ayant subi des anévrismes coronariens modérés ou importants, nous avons évalué l'incidence des différents traitements sur les résultats cliniques et les événements cardiovasculaires indésirables majeurs (ECIM). Résultats: Des anévrismes coronariens modérés ou importants ont été relevés chez 527 patients (32 %). Tous les patients recevaient des immunoglobulines administrées par voie intraveineuse (IgIV); 70 % d'entre eux étaient de sexe masculin, et leur âge médian était de 1,3 an (écart interquartile : de 0,4 an à 4,0 ans). Les traitements d'urgence les plus fréquents comprenaient un seul traitement par IgIV chez 243 patients (46 %), plusieurs traitements par IgIV chez 100 patients (19 %), une association de plusieurs traitements IgIV et de corticostéroïdes chez 75 patients (14 %) et une association de plusieurs traitements IgIV, de corticostéroïdes et d'infliximab chez 44 patients (8 %). Les patients ayant reçu un traitement autre qu'un seul traitement IgIV présentaient des scores z initiaux plus élevés pour le diamètre des artères coronaires (P < 0,001) et un taux plus élevé d'anévrismes coronariens bilatéraux (P < 0,001). En comparaison d'un traitement par IgIV seulement, les traitements d'appoint précoces (administrés dans les trois jours suivant le début du traitement par IgIV) n'ont pas eu d'incidence sur la durée avant la régression des anévrismes coronariens ni sur la survenue d'ECIM, alors que les traitements d'appoint plus tardifs ont été associés à un risque plus élevé d'ECIM et à une régression plus tardive des anévrismes coronariens. Les patients ayant reçu une association d'IgIV et de corticostéroïdes avaient tendance à présenter une régression plus rapide des anévrismes coronariens et un plus faible risque d'ECIM que ceux recevant uniquement un traitement par IgIV (P = 0,07). Un score z initial plus élevé pour un anévrisme coronarien était le facteur prédictif le plus puissant d'une augmentation du score z pendant la période de suivi, d'une probabilité plus faible de régression de l'anévrisme et d'un risque plus élevé d'ECIM. Conclusions: La gravité initiale de l'anévrisme coronarien est plus fortement associée à la persistance de l'anévrisme et à la survenue d'ECIM que le recours à un traitement anti-inflammatoire d'urgence en appoint. Les patients recevant un traitement d'appoint tardif étaient par ailleurs plus susceptibles de présenter des résultats défavorables.

Clinically Suspected Myocarditis Temporally Related to COVID-19 Vaccination in Adolescents and Young Adults: Suspected Myocarditis After COVID-19 Vaccination.

BACKGROUND: Understanding the clinical course and short-term outcomes of suspected myocarditis after the coronavirus disease 2019 (COVID-19) vaccination has important public health implications in the decision to vaccinate youth. METHODS: We retrospectively collected data on patients <21 years old presenting before July 4, 2021, with suspected myocarditis within 30 days of COVID-19 vaccination. Lake Louise criteria were used for cardiac MRI findings. Myocarditis cases were classified as confirmed or probable on the basis of the Centers for Disease Control and Prevention definitions. RESULTS: We report on 139 adolescents and young adults with 140 episodes of suspected myocarditis (49 confirmed, 91 probable) at 26 centers. Most patients were male (n=126, 90.6%) and White (n=92, 66.2%); 29 (20.9%) were Hispanic; and the median age was 15.8 years (range, 12.1-20.3; interquartile range [IQR], 14.5-17.0). Suspected myocarditis occurred in 136 patients (97.8%) after the mRNA vaccine, with 131 (94.2%) after the Pfizer-BioNTech vaccine; 128 (91.4%) occurred after the second dose. Symptoms started at a median of 2 days (range, 0-22; IQR, 1-3) after vaccination. The most common symptom was chest pain (99.3%). Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%), or no anti-inflammatory therapies (8.6%). Twenty-six patients (18.7%) were in the intensive care unit, 2 were treated with inotropic/vasoactive support, and none required extracorporeal membrane oxygenation or died. Median hospital stay was 2 days (range, 0-10; IQR, 2-3). All patients had elevated troponin I (n=111, 8.12 ng/mL; IQR, 3.50-15.90) or T (n=28, 0.61 ng/mL; IQR, 0.25-1.30); 69.8% had abnormal ECGs and arrhythmias (7 with nonsustained ventricular tachycardia); and 18.7% had left ventricular ejection fraction <55% on echocardiogram. Of 97 patients who underwent cardiac MRI at a median 5 days (range, 0-88; IQR, 3-17) from symptom onset, 75 (77.3%) had abnormal findings: 74 (76.3%) had late gadolinium enhancement, 54 (55.7%) had myocardial edema, and 49 (50.5%) met Lake Louise criteria. Among 26 patients with left ventricular ejection fraction <55% on echocardiogram, all with follow-up had normalized function (n=25). CONCLUSIONS: Most cases of suspected COVID-19 vaccine myocarditis occurring in persons <21 years have a mild clinical course with rapid resolution of symptoms. Abnormal findings on cardiac MRI were frequent. Future studies should evaluate risk factors, mechanisms, and long-term outcomes.

Genotyping-by-Sequencing Based Genetic Mapping Identified Major and Consistent Genomic Regions for Productivity and Quality Traits in Peanut.

With an objective of identifying the genomic regions for productivity and quality traits in peanut, a recombinant inbred line (RIL) population developed from an elite variety, TMV 2 and its ethyl methane sulfonate (EMS)-derived mutant was phenotyped over six seasons and genotyped with genotyping-by-sequencing (GBS), Arachis hypogaea transposable element (AhTE) and simple sequence repeats (SSR) markers. The genetic map with 700 markers spanning 2,438.1 cM was employed for quantitative trait loci (QTL) analysis which identified a total of 47 main-effect QTLs for the productivity and oil quality traits with the phenotypic variance explained (PVE) of 10-52% over the seasons. A common QTL region (46.7-50.1 cM) on Ah02 was identified for the multiple traits, such as a number of pods per plant (NPPP), pod weight per plant (PWPP), shelling percentage (SP), and test weight (TW). Similarly, a QTL (7.1-18.0 cM) on Ah16 was identified for both SP and protein content (PC). Epistatic QTL (epiQTL) analysis revealed intra- and inter-chromosomal interactions for the main-effect QTLs and other genomic regions governing these productivity traits. The markers identified by a single marker analysis (SMA) mapped to the QTL regions for most of the traits. Among the five potential candidate genes identified for PC, SP and oil quality, two genes (Arahy.7A57YA and Arahy.CH9B83) were affected by AhMITE1 transposition, and three genes (Arahy.J5SZ1I, Arahy.MZJT69, and Arahy.X7PJ8H) involved functional single nucleotide polymorphisms (SNPs). With major and consistent effects, the genomic regions, candidate genes, and the associated markers identified in this study would provide an opportunity for gene cloning and genomics-assisted breeding for increasing the productivity and enhancing the quality of peanut.

Infliximab versus second intravenous immunoglobulin for treatment of resistant Kawasaki disease in the USA (KIDCARE): a randomised, multicentre comparative effectiveness trial.

BACKGROUND: Although intravenous immunoglobulin (IVIG) is effective therapy for Kawasaki disease, 10-20% of patients have recrudescent fever as a sign of persistent inflammation and require additional treatment. We aimed to compare infliximab with a second infusion of IVIG for treatment of resistant Kawasaki disease. METHODS: In this multicentre comparative effectiveness trial, patients (aged 4 weeks to 17 years) with IVIG resistant Kawasaki disease and fever at least 36 h after completion of their first IVIG infusion were recruited from 30 hospitals across the USA. Patients were randomly assigned (1:1) to second IVIG (2 g/kg over 8-12 h) or intravenous infliximab (10 mg/kg over 2 h without premedication), by using a randomly permuted block randomisation design with block size of two or four. Patients with fever 24 h to 7 days following completion of first study treatment crossed over to receive the other study treatment. The primary outcome measure was resolution of fever at 24 h after initiation of study treatment with no recurrence of fever attributed to Kawasaki disease within 7 days post-discharge. Secondary outcome measures included duration of fever from enrolment, duration of hospitalisation after randomisation, and changes in markers of inflammation and coronary artery Z score. Efficacy was analysed in participants who received treatment and had available outcome values. Safety was analysed in all randomised patients who did not withdraw consent. This clinical trial is registered with ClinicalTrials.gov, NCT03065244. FINDINGS: Between March 1, 2017, and Aug 31, 2020, 105 patients were randomly assigned to treatment and 103 were included in the intention-to-treat population (54 in the infliximab group, 49 in the second IVIG group). Two patients randomised to infliximab did not receive allocated treatment. The primary outcome was met by 40 (77%) of 52 patients in the infliximab group and 25 (51%) of 49 patients in the second IVIG infusion group (odds ratio 0·31, 95% CI 0·13-0·73, p=0·0076). 31 patients with fever beyond 24 h received crossover treatment: nine (17%) in the infliximab group received second IVIG and 22 (45%) in second IVIG group received infliximab (p=0·0024). Three patients randomly assigned to infliximab and two to second IVIG with fever beyond 24h did not receive crossover treatment. Mean fever days from enrolment was 1·5 (SD 1·4) for the infliximab group and 2·5 (2·5) for the second IVIG group (p=0·014). Mean hospital stay was 3·2 days (2·1) for the infliximab group and 4·5 days (2·5) for the second IVIG group (p<0·001). There was no difference between treatment groups for markers of inflammation or coronary artery outcome. 24 (44%) of 54 patients in the infliximab group and 33 (67%) of 49 in the second IVIG group had at least one adverse event. A drop in haemoglobin concentration of at least 2g/dL was seen in 19 (33%) of 58 patients who received IVIG as either their first or second study treatment (three of whom required transfusion) and in three (7%) of 43 who received only infliximab (none required transfusion; p=0·0028). Haemolytic anaemia was the only serious adverse events deemed definitely or probably related to study treatment, and was reported in nine (15%) of 58 patients who received IVIG as either their first or second study treatment and none who received infliximab only. INTERPRETATION: Infliximab is a safe, well tolerated, and effective treatment for patients with IVIG resistant Kawasaki disease, and results in shorter duration of fever, reduced need for additional therapy, less severe anaemia, and shorter hospitalisation compared with second IVIG infusion. FUNDING: Patient Centered Outcomes Research Institute.

COVID-19 Vaccination-Associated Myocarditis in Adolescents.

OBJECTIVES: In this study, we aimed to characterize the clinical presentation, short-term prognosis, and myocardial tissue changes as noted on cardiovascular magnetic resonance (CMR) or cardiac MRI in pediatric patients with coronavirus disease 2019 vaccination-associated myocarditis (C-VAM). METHODS: In this retrospective multicenter study across 16 US hospitals, patients <21 years of age with a diagnosis of C-VAM were included and compared with a cohort with multisystem inflammatory syndrome in children. Younger children with C-VAM were compared with older adolescents. RESULTS: Sixty-three patients with a mean age of 15.6 years were included; 92% were male. All had received a messenger RNA vaccine and, except for one, presented after the second dose. Four patients had significant dysrhythmia; 14% had mild left ventricular dysfunction on echocardiography, which resolved on discharge; 88% met the diagnostic CMR Lake Louise criteria for myocarditis. Myocardial injury as evidenced by late gadolinium enhancement on CMR was more prevalent in comparison with multisystem inflammatory syndrome in children. None of the patients required inotropic, mechanical, or circulatory support. There were no deaths. Follow-up data obtained in 86% of patients at a mean of 35 days revealed resolution of symptoms, arrhythmias, and ventricular dysfunction. CONCLUSIONS: Clinical characteristics and early outcomes are similar between the different pediatric age groups in C-VAM. The hospital course is mild, with quick clinical recovery and excellent short-term outcomes. Myocardial injury and edema are noted on CMR. Close follow-up and further studies are needed to understand the long-term implications and mechanism of these myocardial tissue changes.