Multiomics Signatures of Coagulopathy in a Polytrauma Swine Model Contrasted with Severe Multisystem Injured Patients.

Trauma-induced coagulopathy (TIC) is a leading contributor to preventable mortality in severely injured patients. Understanding the molecular drivers of TIC is an essential step in identifying novel therapeutics to reduce morbidity and mortality. This study investigated multiomics and viscoelastic responses to polytrauma using our novel swine model and compared these findings with severely injured patients. Molecular signatures of TIC were significantly associated with perturbed coagulation and inflammation systems as well as extensive hemolysis. These results were consistent with patterns observed in trauma patients who had multisystem injuries. Here, intervention using resuscitative endovascular balloon occlusion of the aorta following polytrauma in our swine model revealed distinct multiomics alterations as a function of placement location. Aortic balloon placement in zone-1 worsened ischemic damage and mitochondrial dysfunction, patterns that continued throughout the monitored time course. While placement in zone-III showed a beneficial effect on TIC, it showed an improvement in effective coagulation. Taken together, this study highlights the translational relevance of our polytrauma swine model for investigating therapeutic interventions to correct TIC in patients.

Mitral annular disjunction and mitral valve prolapse extrapolating adult data to an adolescent cohort?

PURPOSE OF REVIEW: The aim of this study is to provide an update on mitral valve prolapse (MVP) and mitral annular disjunction (MAD) and who may be at risk for ventricular arrhythmias and sudden cardiac death. RECENT FINDINGS: MVP is generally considered a benign condition. However, a small subset of patients may be at risk for life-threatening ventricular arrhythmias. Among the risk factors identified in adults include patients with bileaflet mitral valves, myxomatous changes, myocardial fibrosis, and the presence of MAD. Advances in multimodal imaging have allowed for improved identification of fibrosis, anatomical valve derangements, and the amount of MAD. Recent guidelines have suggested that patients with MVP with or without MAD may be at risk for life-threatening arrhythmias if they have had prior ventricular arrhythmias, ventricular dysfunction, or unexplained syncope. Yet, extrapolation of adult data to a pediatric cohort with similar MVP and MAD at this juncture is challenging. There is, however, early evidence that some pediatric patients with significant myocardial fibrosis or abnormal tissue Doppler may be at risk for ventricular tachycardia. SUMMARY: Mitral valve prolapse and mitral annular disjunction at times coexist and at other times can be seen as isolated entities. While the incidence of arrhythmic MVP is quite rare, there is increasing evidence that certain select adults with MVP may be at risk for ventricular tachycardia and sudden cardiac death. Future multicenter studies are needed to better understand the natural history of arrhythmic mitral valve disease and how early disease manifestation in children may impact findings now being reported in young adults.

Sex dimorphisms in coagulation: Implications in trauma-induced coagulopathy and trauma resuscitation.

Trauma-induced coagulopathy (TIC) is one of the leading causes of preventable death in injured patients. Consequently, it is imperative to understand the mechanisms underlying TIC and how to mitigate this mortality. An opportunity for advancement stems from the awareness that coagulation demonstrates a strong sex-dependent effect. Females exhibit a relative hypercoagulability compared to males, which persists after injury and confers improved outcomes. The mechanisms underlying sex dimorphisms in coagulation and its protective effect after injury have yet to be elucidated. This review explores sex dimorphisms in enzymatic hemostasis, fibrinogen, platelets, and fibrinolysis, with implications for resuscitation of patients with TIC.

Demonstrating responsiveness of the pediatric cardiac quality of life inventory in children and adolescents undergoing arrhythmia ablation, heart transplantation, and valve surgery.

PURPOSE: Pediatric Cardiac Quality of Life Inventory (PCQLI) is a disease-specific pediatric cardiac health-related quality of life (HRQOL) instrument that is reliable, valid, and generalizable. We aim to demonstrate PCQLI responsiveness in children undergoing arrhythmia ablation, heart transplantation, and valve surgery before and after cardiac intervention. METHODS: Pediatric cardiac patients 8-18 years of age from 11 centers undergoing arrhythmia ablation, heart transplantation, or valve surgery were enrolled. Patient and parent-proxy PCQLI Total, Disease Impact and Psychosocial Impact subscale scores were assessed pre- and 3-12 months follow-up. Patient clinical status was assessed by a clinician post-procedure and dichotomized into markedly improved/improved and no change/worse/much worse. Paired t-tests examined change over time. RESULTS: We included 195 patient/parent-proxies: 12.6 ± 3.0 years of age; median follow-up time 6.7 (IQR = 5.3-8.2) months; procedural groups - 79 (41%) ablation, 28 (14%) heart transplantation, 88 (45%) valve surgery; clinical status - 164 (84%) markedly improved/improved, 31 (16%) no change/worse/much worse. PCQLI patient and parent-proxies Total scores increased (p ≤ 0.013) in each intervention group. All PCQLI scores were higher (p < 0.001) in the markedly improved/improved group and there were no clinically significant differences in the PCQLI scores in the no difference/worse/much worse group. CONCLUSION: The PCQLI is responsive in the pediatric cardiac population. Patients with improved clinical status and their parent-proxies reported increased HRQOL after the procedure. Patients with no improvement in clinical status and their parent-proxies reported no change in HRQOL. PCQLI may be used as a patient-reported outcome measure for longitudinal follow-up and interventional trials to assess HRQOL impact from patient and parent-proxy perspectives.

It is important to have quality of life (QOL) measures that are sensitive to change in QOL before and after procedures and to be sensitive to change over time. The Pediatric Cardiac Quality of Life Inventory (PCQLI) is a QOL measure specifically developed for children with cardiac disease. This study assessed the responsiveness of the PCQLI to detect change in QOL over time. QOL in Children and adolescents who were being treated for abnormal heart rhythms, heart transplantation, and aortic, pulmonary, or mitral valve surgery were assessed before and after their procedure. Children and adolescents with improved clinical status post-procedure, and their parents, reported better QOL after the procedure. Patients with no improvement from a cardiac standpoint and their parents reported no change in QOL after their procedure. The PCQLI may be used to assess QOL before and after cardiac procedures or medical treatment and follow QOL over time.

Multiple recurrent supraventricular tachycardia in infantile tuberous sclerosis complex: management requiring triple-drug therapy.

We report the case of a female neonate admitted to the neonatal ICU with a rapid, narrow-complex tachyarrhythmia determined to be supraventricular tachycardia. Multimodality imaging and genetic testing confirmed a diagnosis of tuberous sclerosis complex with multiple cardiac rhabdomyomas. At 13 days of age, the patient was readmitted, exhibiting recurrent supraventricular tachycardia non-responsive to first-line treatment. Management required triple-drug therapy, whereafter the patient remained stable without recurrences. This is a rare report of supraventricular tachycardia in a functionally normal heart with the occurrence of supraventricular tachycardia due to structural abnormalities, with the possibility of multiple concealed accessory pathways.

What Happens on Call Doesn't Stay on Call. The Effects of In-house Call on Acute Care Surgeons' Sleep and Burnout: Results of the Surgeon Performance (SuPer) Trial.

OBJECTIVE: We sought to quantify the effects of in-house call(IHC) on sleep patterns and burnout among acute care surgeons (ACS). BACKGROUND: Many ACS take INC, which leads to disrupted sleep and high levels of stress and burnout. METHODS: Physiological and survey data of 224 ACS with IHC were collected over 6 months. Participants continuously wore a physiological tracking device and responded to daily electronic surveys. Daily surveys captured work and life events as well as feelings of restfulness and burnout. The Maslach Burnout Inventory (MBI) was administered at the beginning and end of the study period. RESULTS: Physiological data were recorded for 34,135 days, which includes 4389 nights of IHC. Feelings of moderate, very, or extreme burnout occurred 25.7% of days and feelings of being moderately, slightly, or not at all rested occurred 75.91% of days. Decreased amount of time since the last IHC, reduced sleep duration, being on call, and having a bad outcome all contribute to greater feelings of daily burnout ( P <0.001). Decreased time since last call also exacerbates the negative effect of IHC on burnout ( P <0.01). CONCLUSIONS: ACS exhibit lower quality and reduced amount of sleep compared with an age-matched population. Furthermore, reduced sleep and decreased time since the last call led to increased feelings of daily burnout, accumulating in emotional exhaustion as measured on the MBI. A reevaluation of IHC requirements and patterns as well as identification of countermeasures to restore homeostatic wellness in ACS is essential to protect and optimize our workforce.

Omics Signatures of Tissue Injury and Hemorrhagic Shock in Swine.

OBJECTIVE: Advanced mass spectrometry methods were leveraged to analyze both proteomics and metabolomics signatures in plasma upon controlled tissue injury (TI) and hemorrhagic shock (HS)-isolated or combined-in a swine model, followed by correlation to viscoelastic measurements of coagulopathy via thrombelastography. BACKGROUND: TI and HS cause distinct molecular changes in plasma in both animal models and trauma patients. However, the contribution to coagulopathy of trauma, the leading cause of preventable mortality in this patient population remains unclear. The recent development of a swine model for isolated or combined TI+HS facilitated the current study. METHODS: Male swine (n=17) were randomized to either isolated or combined TI and HS. Coagulation status was analyzed by thrombelastography during the monitored time course. The plasma fractions of the blood draws (at baseline; end of shock; and at 30 minutes, 1, 2, and 4 hours after shock) were analyzed by mass spectrometry-based proteomics and metabolomics workflows. RESULTS: HS-isolated or combined with TI-caused the most severe omic alterations during the monitored time course. While isolated TI delayed the activation of coagulation cascades. Correlation to thrombelastography parameters of clot strength (maximum amplitude) and breakdown (LY30) revealed signatures of coagulopathy which were supported by analysis of gene ontology-enriched biological pathways. CONCLUSION: The current study provides a comprehensive characterization of proteomic and metabolomic alterations to combined or isolated TI and HS in a swine model and identifies early and late omics correlates to viscoelastic measurements in this system.

Endothelial Cell Calcium Influx Mediates Trauma-induced Endothelial Permeability.

OBJECTIVE: We aimed to investigate if ex vivo plasma from injured patients causes endothelial calcium (Ca2+) influx as a mechanism of trauma-induced endothelial permeability. SUMMARY BACKGROUND DATA: Endothelial permeability after trauma contributes to post-injury organ dysfunction. While the mechanisms remain unclear, emerging evidence suggests intracellular Ca2+ signaling may play a role. METHODS: Ex vivo plasma from injured patients with "Low Injury/Low Shock" (injury severity score [ISS]<15, base excess [BE])≥-6mEq/L) and "High Injury/High Shock" (ISS≥15, BE<-6mEq/L) were used to treat endothelial cells. Experimental conditions included Ca2+ removal from the extracellular buffer, cyclopiazonic acid pre-treatment to deplete intracellular Ca2+ stores, and GSK2193874 pre-treatment to block the TRPV4 Ca2+ channel. Live cell fluorescence microscopy and ECIS were used to assess cytosolic Ca2+ increases and permeability, respectively. Western blot and live cell actin staining were used to assess myosin light chain (MLC) phosphorylation and actomyosin contraction. RESULTS: Compared to Low Injury/Low Shock plasma, High Injury/High Shock induced greater cytosolic Ca2+ increase. Cytosolic Ca2+ increase, MLC phosphorylation, and actin cytoskeletal contraction were lower without extracellular Ca2+ present. High Injury/High Shock plasma did not induce endothelial permeability without extracellular Ca2+ present. TRPV4 inhibition lowered trauma plasma-induced endothelial Ca2+ influx and permeability. CONCLUSIONS: This study illuminates a novel mechanism of post-injury endotheliopathy involving Ca2+ influx via the TRPV4 channel. TRPV4 inhibition mitigates trauma-induced endothelial permeability. Moreover, widespread endothelial Ca2+ influx may contribute to trauma-induced hypocalcemia. This study provides the mechanistic basis for the development of Ca2+-targeted therapies and interventions in the care of severely injured patients.

Differences in Quality of Life in Children Across the Spectrum of Congenital Heart Disease.

OBJECTIVE: To create complexity groups based upon a patient's cardiac medical history and to test for group differences in health-related quality of life (HRQOL). METHODS: Patients 8-18 years with congenital heart disease (CHD) and parent-proxies from the Pediatric Cardiac Quality of Life Inventory (PCQLI) Testing Study were included. Outcome variables included PCQLI Total, Disease Impact, and Psychosocial Impact scores. Using a patient's medical history (cardiac, neurologic, psychological, and cognitive diagnosis), latent class analysis (LCA) was used to create CHD complexity groups. Covariates included demographics and burden of illness (number of: school weeks missed, physician visits in the past year, and daily medications). Generalized estimation equations tested for differences in burden of illness and patient and parent-proxy PCQLI scores. RESULTS: Using 1482 CHD patients (60% male; 84% white; age 12.3 ± 3.0 years), latent class analysis (LCA) estimates showed 4 distinct CHD complexity groups (Mild, Moderate 1, Moderate 2, and Severe). Increasing CHD complexity was associated with increased risk of learning disorders, seizures, mental health problems, and history of stroke. Greater CHD complexity was associated with greater burden of illness (P < .01) and lower patient- and parent-reported PCQLI scores (P < .001). CONCLUSIONS: LCA identified 4 congenital heart disease (CHD) complexity groupings. Increasing CHD complexity was associated with higher burden of illness and worse patient- and parent-reported HRQOL.

Human Challenge Studies for Cholera.

The human challenge model permits an estimate of the vaccine protection against moderate and severe cholera. It eliminates the difficulty in setting up a vaccine study in endemic area including uncertainties about the incidence of cholera and the logistic arrangements for capturing those who do/do not become ill. Valuable information from small groups of subjects can be obtained in a short period. Under proper precautions and study design, the challenge model is safe and efficient. Although the model has evolved since it was introduced over 50 years ago, it has been used extensively to test vaccine efficacy. Vaccine licensure has resulted from data obtained using the human challenge model. In addition, the model has been used to: (1) Establish and validate a standardized inoculum, (2) Identify immune markers and immune responses, (3) Determine natural immunity (in re-challenge studies), (4) Identify the role of the gastric acid barrier in preventing cholera infection, (5) Show homologous and heterologous infection-derived immunity, and (6) Test the efficacy of anti-diarrheal/anti-secretory small molecules. The aim of this chapter is to present an overview on the state of the art for human challenge models used to study cholera and new medical interventions against it.

Building resilient heart center teams.

PURPOSE OF REVIEW: The purpose of this review is to move beyond measures to improve individual resilience but to focus on measures to achieve better team resilience. RECENT FINDINGS: The COVID pandemic, shortages of heath care workers, and subsequent viral resurgence in 2022 placed tremendous stress on pediatric healthcare systems. Much has been written about individual wellness, mindfulness, and strategies to be a more resilient individual. However, little has been written on the importance of team resilience. Resilient teams work together to overcome daily stressors and challenges. Although leaders must create and foster a collaborative culture to establish cohesive and resilient teams; it also requires tremendous institutional support. Four key factors have emerged with regards to successful team resilience: candor, humility, resourcefulness, and compassion and empathy. This article discusses the key elements required for resilient teams to not only survive but also to thrive. SUMMARY: Effective heart centers, like the symphony, are a collection of individuals all coming together to care for a child or create a singular piece of music. Heart centers without effective leaders will most certainly fail, but even with the most accomplished and passionate leaders, there must be administrative institutional support and a shared vision.

Omics markers of platelet transfusion in trauma patients.

BACKGROUND: Even in the era of the COVID-19 pandemic, trauma remains the global leading cause of mortality under the age of 49. Trauma-induced coagulopathy is a leading driver of early mortality in critically ill patients, and transfusion of platelet products is a life-saving intervention to restore hemostasis in the bleeding patient. However, despite extensive functional studies based on viscoelastic assays, limited information is available about the impact of platelet transfusion on the circulating molecular signatures in trauma patients receiving platelet transfusion. MATERIALS AND METHODS: To bridge this gap, we leveraged metabolomics and proteomics approaches to characterize longitudinal plasma samples (n = 118; up to 11 time points; total samples: 759) from trauma patients enrolled in the Control Of Major Bleeding After Trauma (COMBAT) study. Samples were collected in the field, in the emergency department (ED), and at intervals up to 168 h (7 days) post-hospitalization. Transfusion of platelet (PLT) products was performed (n = 30; total samples: 250) in the ED through 24 h post-hospitalization. Longitudinal plasma samples were subjected to mass spectrometry-based metabolomics and proteomics workflows. Multivariate analyses were performed to determine omics markers of transfusion of one, two, three, or more PLT transfusions. RESULTS: Higher levels of tranexamic acid (TXA), inflammatory proteins, carnitines, and polyamines were detected in patients requiring PLT transfusion. Correlation of PLT units with omics data suggested sicker patients required more units and partially overlap with the population requiring transfusion of packed red blood cell products. Furthermore, platelet activation was likely increased in the most severely injured patients. Fatty acid levels were significantly lower in PLT transfusion recipients (at time of maximal transfusion: Hour 4) compared with non-recipients, while carnitine levels were significantly higher. Fatty acid levels restore later in the time course (e.g., post-PLT transfusion). DISCUSSION: The present study provides the first multi-omics characterization of platelet transfusion efficacy in a clinically relevant cohort of trauma patients. Physiological alterations following transfusion were detected, highlighting the efficacy of mass spectrometry-based omics techniques to improve personalized transfusion medicine. More specialized clinical research studies focused on PLT transfusion, including organized pre and post transfusion sample collection and limitation to PLT products only, are required to fully understand subsequent metabolomic and proteomic alterations.

Improving Bowel Management in Children With Spina Bifida.

OBJECTIVES: In individuals with spina bifida (SB), bowel incontinence is associated with lower quality of life and lower likelihood of employment. In an effort to maximize bowel continence in children and adolescents, we created a bowel management assessment and follow-up protocol in a multidisciplinary clinic. Here we report the results of this protocol using quality-improvement methodology. METHODS: Continence was defined as no unplanned bowel movements. Our protocol involved: (1) a standardized 4-item questionnaire about bowel continence and consistency; (2) if the patient was not achieving continence, an intervention starting with oral medication (stimulant and/or osmotic laxatives), and/or suppositories (glycerin or bisacodyl) followed by an escalation to trans-anal irrigation, or continence surgery; and (3) follow-up phone calls at regular intervals to monitor progress and make changes as needed. Results are summarized with descriptive statistics. RESULTS: We screened 178 eligible patients in the SB clinic. Eighty-eight agreed to participate in the bowel management program. Of those who did not participate, the majority (68/90, 76%) were already achieving continence with their bowel regimen. Of children in the program, most (68/88, 77%) had a diagnosis of meningomyelocoele. At 1 year, the proportion of patients who were bowel accident free improved to 46% (vs 22% initially, P = 0.0007). CONCLUSIONS: A standardized bowel management protocol, primarily the use of suppositories and trans-anal irrigation to achieve social continence, as well as frequent telephone follow-up, can reduce bowel incontinence in children and adolescents with SB.

Cigarette Smoke Exposure and Acute Respiratory Distress Syndrome in Sepsis: Epidemiology, Clinical Features, and Biologic Markers.

Rationale: Cigarette smoke exposure is associated with an increased risk of developing acute respiratory distress syndrome (ARDS) in trauma, transfusion, and nonpulmonary sepsis. It is unknown whether this relationship exists in the general sepsis population. Furthermore, it is unknown if patients with ARDS have differences in underlying biology based on smoking status. Objectives: To assess the relationship between cigarette smoke exposure and ARDS in sepsis and identify tobacco-related biomarkers of lung injury. Methods: We studied a prospective cohort of 592 patients with sepsis from 2009 to 2017. Plasma cotinine and urine NNAL [urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol] were measured to categorize smoking status. Plasma biomarkers of inflammation and lung injury were measured, including in a smaller cohort of trauma patients with ARDS to increase generalizability. Measurements and Main Results: Passive and active smoking were associated with increased odds of developing ARDS in patients with sepsis. Among patients with sepsis and ARDS, active cigarette smokers were younger and had lower severity of illness than nonsmokers. Patients with ARDS with cigarette smoke exposure had lower plasma levels of IL-8 (P = 0.01) and sTNFR-1 (soluble tumor necrosis factor 1; P = 0.01) compared with those without exposure. Similar biomarker patterns were observed in blunt trauma patients with ARDS. Conclusions: Passive and active smoking are associated with an increased risk of developing ARDS in patients with pulmonary and nonpulmonary sepsis. Among patients with ARDS, those with cigarette smoke exposure have less systemic inflammation, while active smokers also have lower severity of illness compared with nonsmokers, suggesting that smoking contributes to biological heterogeneity in ARDS.

A Prospective Evaluation of Arrhythmias in a Large Tertiary Neonatal Intensive Care Unit.

Arrhythmias in the neonatal period are common and can be classified as bradyarhythmias and tachyarrhythmias and as benign or non-benign. Neonatal arrhythmias are further differentiated between those with abnormalities in generation (non-sinus) and those with abnormalities in propagation. Because the neonatal myocardium is immature and operates at the peak of the Starling curve, significant changes in heart rate can result in a decline in cardiac output and compromise end-organ perfusion. This is especially true for premature neonates, those critically ill, or those with concomitant congenital heart disease. While sustained arrhythmias are frequently witnessed and recorded in tertiary neonatal intensive care units (NICU) very little data exist on the observance of non-sustained brady- or tachyarrhythmias in this cohort. No prospective study has been performed on all neonates admitted to a large tertiary NICU throughout their entire stay. The purpose of this study was to prospectively evaluate the prevalence and type of arrhythmias in a large NICU population from admission to discharge. All neonates admitted to the NICU at Inova Children's Hospital at Inova Fairfax Medical Campus between January 1, 2021 and April 1, 2021 were prospectively evaluated from admission to hospital discharge via continuous bedside monitoring reviewed every 24 h. Concerning telemetry strips were reviewed by two team members as well as the senior electrophysiologist. Two-hundred and one neonates (mean gestational age = 344/7 weeks) were enrolled in the study. Admission length ranged from 1 to 195 days (total of 5624 patient days, median 16 days). Overall, 68% (N = 137) of admissions had one or more arrhythmias, the most common of which was sinus tachycardia (65%, N = 130), followed by sinus bradycardia (30%, N = 60). Clinically relevant arrhythmias were diagnosed in 6.5% of neonates. During the study period there were four deaths, none of which were directly attributable to a primary arrhythmia. Approximately 68% of neonates exhibited at least one arrhythmia. Although the vast majority of these arrhythmias were benign, clinically relevant arrhythmias were observed in 6.5%. Patients admitted to the NICU appear to have a relatively high burden of benign arrhythmias, but a relatively low burden of pathologic arrhythmias.

Patterns of Electrocardiographic Abnormalities in Children with Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM), a common cardiomyopathy in children, is an important cause of morbidity and mortality. Early recognition and appropriate management are important. An electrocardiogram (ECG) is often used as a screening tool in children to detect heart disease. The ECG patterns in children with HCM are not well described.ECGs collected from an international cohort of children, and adolescents (≤ 21 years) with HCM were reviewed. 482 ECGs met inclusion criteria. Age ranged from 1 day to 21 years, median 13 years. Of the 482 ECGs, 57 (12%) were normal. The most common abnormalities noted were left ventricular hypertrophy (LVH) in 108/482 (22%) and biventricular hypertrophy (BVH) in 116/482 (24%) Of the patients with LVH/BVH (n = 224), 135 (60%) also had a strain pattern (LVH in 83, BVH in 52). Isolated strain pattern (in the absence of criteria for hypertrophy) was seen in 43/482 (9%). Isolated pathologic Q waves were seen in 71/482 (15%). Pediatric HCM, 88% have an abnormal ECG. The most common ECG abnormalities were LVH or BVH with or without strain. Strain pattern without hypertrophy and a pathologic Q wave were present in a significant proportion (24%) of patients. Thus, a significant number of children with HCM have ECG abnormalities that are not typical for "hypertrophy". The presence of the ECG abnormalities described above in a child should prompt further examination with an echocardiogram to rule out HCM.

Advocacy at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.

The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.

Succinate Activation of SUCNR1 Predisposes Severely Injured Patients to Neutrophil-mediated ARDS.

OBJECTIVES: Identify the metabolites that are increased in the plasma of severely injured patients that developed ARDS versus severely injured patients that did not, and assay if these increased metabolites prime pulmonary sequestration of neutrophils (PMNs) and induce pulmonary sequestration in an animal model of ARDS. We hypothesize that metabolic derangement due to advanced shock in critically injured patients leads to the PMNs, which serves as the first event in the ARDS. Summary of Background Data: Intracellular metabolites accumulate in the plasma of severely injured patients. METHODS: Untargeted metabolomics profiling of 67 critically injured patients was completed to establish a metabolic signature associated with ARDS development. Metabolites that significantly increased were assayed for PMN priming activity in vitro. The metabolites that primed PMNs were tested in a 2-event animal model of ARDS to identify a molecular link between circulating metabolites and clinical risk for ARDS. RESULTS: After controlling for confounders, 4 metabolites significantly increased: creatine, dehydroascorbate, fumarate, and succinate in trauma patients who developed ARDS ( P < 0.05). Succinate alone primed the PMN oxidase in vitro at physiologically relevant levels. Intravenous succinate-induced PMN sequestration in the lung, a first event, and followed by intravenous lipopolysaccharide, a second event, resulted in ARDS in vivo requiring PMNs. SUCNR1 inhibition abrogated PMN priming, PMN sequestration, and ARDS. Conclusion: Significant increases in plasma succinate post-injury may serve as the first event in ARDS. Targeted inhibition of the SUCNR1 may decrease ARDS development from other disease states to prevent ARDS globally.

Detection and management of milk allergy: Delphi consensus study.

BACKGROUND: There is significant overdiagnosis of milk allergy in young children in some countries, leading to unnecessary use of specialized formula. This guidance, developed by experts without commercial ties to the formula industry, aims to reduce milk allergy overdiagnosis and support carers of children with suspected milk allergy. METHODS: Delphi study involving two rounds of anonymous consensus building and an open meeting between January and July 2021. Seventeen experts in general practice, nutrition, midwifery, health visiting, lactation support and relevant areas of paediatrics participated, located in Europe, North America, Middle East, Africa, Australia and Asia. Five authors of previous milk allergy guidelines and seven parents provided feedback. FINDINGS: Participants agreed on 38 essential recommendations through consensus. Recommendations highlighted the importance of reproducibility and specificity for diagnosing milk allergy in children with acute or delayed symptoms temporally related to milk protein ingestion; and distinguished between children directly consuming milk protein and exclusively breastfed infants. Consensus was reached that maternal dietary restriction is not usually necessary to manage milk allergy, and that for exclusively breastfed infants with chronic symptoms, milk allergy diagnosis should only be considered in specific, rare circumstances. Consensus was reached that milk allergy diagnosis does not need to be considered for stool changes, aversive feeding or occasional spots of blood in stool, if there is no temporal relationship with milk protein ingestion. When compared with previous guidelines, these consensus recommendations resulted in more restrictive criteria for detecting milk allergy and a more limited role for maternal dietary exclusions and specialized formula. INTERPRETATION: These new milk allergy recommendations from non-conflicted, multidisciplinary experts advise narrower criteria, more prominent support for breastfeeding and less use of specialized formula, compared with current guidelines.

Arrhythmogenic right ventricular cardiomyopathy in the pediatric population.

PURPOSE OF REVIEW: Review the current state of the art of arrhythmogenic right ventricular cardiomyopathy (ARVC) diagnosis and risk stratification in the pediatric population. RECENT FINDINGS: ARVC is an inherited cardiomyopathy characterized by progressive myocyte loss and fibrofatty replacement of predominantly the right ventricle and high risk of ventricular arrhythmias and sudden cardiac death (SCD). ARVC is one of the leading causes of arrhythmic cardiac arrest in young people. Early diagnosis and accurate risk assessment are challenging, especially in children who often exhibit little to no phenotype, even if genotype positive. Multimodal imaging provides more detailed assessment of the right ventricle and has been shown in pediatric patients to identify earlier preclinical disease expression. Identification of patients with ARVC allows the clinician to intervene early with appropriate exercise restrictions, even if genotype positive only without phenotypic expression. Emphasis should be placed on stratifying the patient's risk of ventricular arrhythmias and SCD. SUMMARY: ARVC is a challenging diagnosis to make in adolescents who often do not exhibit clinical symptoms. Newer multimodal imaging techniques and improvements in genetic testing and biomarkers should help improve early diagnosis. Exercise restriction for children with ARVC has been shown to reduce disease advancement and decreases the risk of a life-threatening event.