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Background: Immune effector cell (IEC) therapies, including chimeric antigen receptor (CAR)-modified T-cell therapy, have shown efficacy in pediatric B-cell acute lymphoblastic leukemia (B-ALL) and are being investigated for other malignancies. A common toxicity associated with IEC therapy is cytokine release syndrome (CRS), which can lead to cardiovascular decompensation due to systemic inflammation. Data are limited regarding cardiovascular adverse effects in children. This study aims to describe the cardiovascular adverse effect profile of IEC therapies in pediatric patients with hematologic and solid tumor malignancies., Methods: We retrospectively reviewed patients who received IECs directed towards various targets in patients with hematologic, solid, and brain tumor malignancies from January 2014 to June 2023 at Texas Children's Hospital. The primary end point was hypotension requiring vasoactive support and/or heart failure within 30 days of infusion., Results: A total of 203 patients met inclusion criteria. Pretreatment echocardiogram was available for 142 (70%) pediatric patients, of whom 140 (96%) had normal baseline systolic function. Hypotension requiring vasoactive support occurred in 26 (13%) patients. Hematologic malignancy indications (p = 0.002), total body irradiation (TBI) (p = 0.002), and allogenic hematopoietic stem cell transplants (HCT) (p = 0.035) were associated with increased risk of hypotension requiring vasoactive support. Follow-up echocardiograms were available for 14 patients who met the primary end point, and all showed return to baseline within 6 months., Conclusions: Significant hemodynamic compromise occurred in a minority of patients treated with IEC therapies. All experiencing cardiac dysfunction had recovery of function, and there was no cardiovascular-related mortality., (© 2025 Wiley Periodicals LLC.)

Objective: Neurodevelopmental delay is common in children who undergo surgery for Congenital Heart Disease (CHD) in infancy. Cardiac surgery associated acute kidney injury (CS-AKI) occurs frequently in the paediatric cardiac Intensive care unit (ICU). Cardiac surgery associated acute kidney injury (CS-AKI) is associated with worse neurodevelopmental scores and delay in cognitive, language, and motor domains in children with CHD. No known data exist regarding the association of CS-AKI and motor and language subscales. In this study, we explored the relationship between CS-AKI and receptive and expressive language, as well as gross and fine motor delay., Methods: This was a single centre retrospective observational cohort study. Children who underwent surgery for CHD and developed recurrent CS-AKI in the first year of life who had follow-up neurodevelopmental testing using the Bayley Scale of Infant Development Version III were included. Neurodevelopmental delay subscales assessed included: receptive and expressive language, fine and motor skills., Results: The study cohort included 203 children. Recurrent CS-AKI was significantly associated with lower scores in receptive and expressive language, as well as fine and gross motor on unadjusted analyses. On adjusted analyses, recurrent CS-AKI was significantly associated with severe receptive language delay., Conclusion: The independent association of recurrent CS-AKI with severe language delay in children who undergo surgery for CHD in infancy is novel. Our findings may contribute to the understanding of language impairment in this population. Further studies are required to better understand this relationship and any potentially modifiable factors.

Objective: CHD predisposes children to neurodevelopmental delays. Frequent, prolonged hospitalisations during infancy prevent children with heart disease from participating in recommended language and cognitive development programmes, such as outpatient early childhood literacy programmes, and contribute to caregiver stress, a risk factor for adverse developmental outcomes. This study aims to describe the implementation of a single-centre inpatient early childhood literacy programme for hospitalised infants with heart disease and assess its impact on reading practices and patient-family hospital experience., Methods: Admitted infants ≤1 year old receive books, a calendar to track reading frequency, and reading guidance at regular intervals. Voluntary feedback is solicited from caregivers using an anonymous, QR-code survey on books. A prospective survey also assessed programme impact on hospital experience., Results: From February 2021 to November 2023, the Books@Heart programme provided 1,293 books to families of 840 infants, of whom 110 voluntarily submitted feedback. Caregivers reported a significant improvement in access to books (p < 0.001) and increased reading frequency after learning about Books@Heart ( p = 0.003), with the proportion reading to their child daily increasing from 27% to 62%. Among 40 prospective survey responses, caregivers reported feeling a sense of personal fulfillment (60%), self-confidence (30%), connection (98%), and personal well-being (40%) while reading to their child., Conclusion: An inpatient early childhood literacy programme is a well-received intervention for infants with heart disease that promotes development, improves book access, increases reading exposure, and engages families. Further studies are needed to assess its impact on sustained reading practices and neurodevelopmental outcomes.

Introduction: Surgeons and military personnel are subjected to high-stress scenarios, which leads to greater rates of burnout. There is room to optimize performance and longevity in these careers by better understanding the body's stress response and applying it to stress management training. This study aims to understand the physiological response in those engaged in trauma scenarios by examining 6 hormones and 42 cytokines during the Intensive Surgical and Trauma Skills Course held at Strategic Operations Inc in San Diego, CA., Methods: Thirty-seven military medical students participated in full immersion, hyper-realistic, and experiential mass casualty high-stress scenarios. Participants were exposed to both operating and emergency room scenarios. Saliva samples were taken after stress inoculation (postinoculation) and again 1 hr after each scenario (recovery). Saliva samples were analyzed using plex assays from Eve Technologies. Data were grouped and analyzed by location and timing using mixed effect nonlinear models. Distributions were compared by location and were analyzed with respect to biomarker levels over the 4-day training period., Results: For emergency room scenarios, there was a decrease in the following cytokines from postinoculation to recovery: epidermal growth factor (EGF), granulocyte colony stimulating factor (G-CSF), epidermal growth factor, granulocyte colony stimulating factor, interleukin 1alpha (IL-1α), interleukin 1beta (IL-1 β), IL-1RA, IL-4, IL-8, IL-10, IL-18, monocyte chemotactic protein (MCP) 1, macrophage colony stimulating factor (M-CSF), macrophage derived chemokine (MDC), CXC motif ligand 9 (MIG/CXCL9), regulated upon activation, normal T cell expressed and secreted (RANTES), and vascular endothelial growth factor (P < 0.05, t > 3.0). For operating room scenarios, there was a decrease in the following cytokines: EGF, G-CSF, IL-1α, IL-1 β, IL-1RA, IL-6, IL-8, IL-10, IL-18, M-CSF, MDC, MIG/CXCL9, RANTES, and tumor necrosis factor alpha. In operating room scenarios, an increase in the hormone levels of progesterone and triodothyronine were observed. The cytokines observed in both groups included EGF, IL-1α, RANTES, MDC, EGF, G-CSF, IL-1RA, IL-18, MIG/CXCL9, IL-8, IL-1β, M-CSF, and IL-10. These significant biomarkers were also graphed and visualized as variable throughout the week., Conclusions: These preliminary data narrow a wide array of stress biomarkers to a smaller, significant group. Surgeons and military personnel are subjected to extraordinary levels of stress with narrow margins for error. To optimize performance and outcomes, it is pertinent to understand the physiological stress response. Future investigation and pairing of cytokine measurements with neuropsychological and performance-based testing will target opportunities to direct training and identify profiles of individuals well suited for stressful environments., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Zwitterionic polysaccharides (ZPSs) present on the surface of a common gut commensal Bacteroides fragilis are endowed with unique immunological properties as they can directly bind to T-cells in the absence of protein conjugation. ZPSs are therefore considered to be potential antigens for the development of totally carbohydrate-based vaccines. Herein, we disclose the first total synthesis of a highly branched phosphorylated zwitterionic capsular polysaccharide repeating unit of Bacteroides fragilis. The hexasaccharide repeating unit bearing six different monosaccharides comprises three 1,2-cis-glycosidic linkages, a challenging 1,2-trans linkage in D-QuipNAc-β-(1→4)-D-Gal motif, and a 2-aminoethyl phosphonate appendage. The synthesis of target ZPS was accomplished utilizing an expeditious, highly stereoselective and convergent (1 + 2 + 2 + 1) one-pot glycosylation strategy. The striking features include efficient synthesis of rare deoxy amino sugars D- and L-quinovosamine, stereoselective installation of three 1,2-cis glycosidic linkages, glycosylation of D-quinovosamine donor with a sterically crowded, poorly reactive 4-OH galactose moiety, as well as late stage phosphorylation., (© 2024. The Author(s).)

In addition to controlling smooth muscle tone in coronary vessels, endothelial cells also influence subjacent cardiomyocyte growth. Because heparanase, with exclusive expression in endothelial cells, enables extracellular matrix remodeling, angiogenesis, metabolic reprogramming, and cell survival, it is conceivable that it could also encourage development of cardiac hypertrophy. Global heparanase overexpression resulted in physiologic cardiac hypertrophy, likely an outcome of HSPG clustering and activation of hypertrophic signaling. The heparanase autocrine effect of releasing neuregulin-1 could have also contributed to this overexpression. Hyperglycemia induced by streptozotocin-induced diabetes sensitized the heart to flow-induced release of heparanase and neuregulin-1. Despite this excess secretion, progression of diabetes caused significant gene expression changes related to mitochondrial metabolism and cell death that led to development of pathologic hypertrophy and heart dysfunction. Physiologic cardiac hypertrophy was also observed in rats with cardiomyocyte-specific vascular endothelial growth factor B overexpression. When perfused, hearts from these animals released significantly higher amounts of both heparanase and neuregulin-1. However, subjecting these animals to diabetes triggered robust transcriptome changes related to metabolism and a transition to pathologic hypertrophy. Our data suggest that in the absence of mechanisms that support cardiac energy generation and prevention of cell death, as seen after diabetes, there is a transition from physiologic to pathologic cardiac hypertrophy and a decline in cardiac function., (© 2024 by the American Diabetes Association.)

While significant progress has been made in reducing disparities within the US health care system, notable gaps remain. This article explores existing disparities within pediatric congenital heart disease care. Congenital heart disease, the most common birth defect and a leading cause of infant death, has garnered substantial attention, revealing certain disparities within the US health care system. Factors such as race, ethnicity, insurance coverage, socioeconomic status, and geographic location are all commonalities that significantly affect health disparities in pediatric congenital heart disease. This comprehensive review sheds light on disparities from diverse perspectives in pediatric care, demonstrates the inequities and inequalities leading to these disparities, presents effective solutions, and issues a call to action for providers, institutions, and the health care system. Recognizing and addressing these disparities is imperative for ensuring equitable care and enhancing the long-term well-being of children affected by congenital heart disease. Implementing robust, evidence-based frameworks that promote responsible and safe interventions is fundamental to enduring change.

Background: Traditionally, low cardiac output has been considered the primary hemodynamic driver of renal function and injury. Adult data suggest that central venous pressure (CVP) is a more important factor., Objectives: The authors hypothesized that in children with cardiovascular disease, higher CVP predicts lower estimated glomerular filtration rate (eGFR) and worsening renal function (WRF)., Methods: We performed a single-center cohort study of patients aged 3 months to 21 years with biventricular circulation undergoing cardiac catheterization. Pearson's correlation and linear and Cox regression analyses were performed to determine associations with eGFR at the time of catheterization and WFR within 180 days after catheterization., Results: 312 patients had median age 7.9 years (IQR: 2.3 to 14.5 years), median eGFR 97 mL/min/1.73 m 2 (IQR: 81-118 mL/min/1.73 m 2 ), median CVP 7 mm Hg (IQR: 5-9 mm Hg), and median cardiac index 3.7 mL/min/m 2 (IQR: 2.9-4.6 mL/min/m 2 ). Nearly half (48%) were transplant recipients. In multivariable analysis, CVP was independently associated with eGFR (β = -2.65; 95% CI: -4.02, -1.28; P  < 0.001), as was being a transplant recipient (β = -10.20; 95% CI: -17.74, -2.65; P  = 0.008), while cardiac index was not. Fifty-one patients (16%) developed WRF. In a proportional hazards model adjusting for cardiac index, only higher CVP (HR: 1.10; 95% CI: 1.04-1.17; P  = 0.002) and greater contrast volume by weight (HR: 1.05; 95% CI: 1.01-1.10; P  = 0.021) predicted WRF. CVP ≥7 mm Hg likewise predicted WRF (HR: 2.57; 95% CI: 1.29-5.12; P  = 0.007)., Conclusions: Among children with a spectrum of cardiovascular disease, higher CVP is associated with lower eGFR and development of WRF, independent of cardiac index., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Mental health conditions are a common comorbidity among children living with heart disease. Children with congenital heart disease are more likely to have a mental health condition than their unaffected peers or peers with other chronic illnesses, and mental health risk persists across their lifetime. While poorer mental health in adults with congenital heart disease is associated with worse overall health outcomes, the association between mental health and cardiac outcomes for children with heart disease remains unknown. Despite this, it is suspected that mental health conditions go undiagnosed in children with heart disease and that many affected children and adolescents do not receive optimal mental health care. In this article, we review mental health in congenital heart disease across the lifespan, across domains of care, and across diagnoses. Further directions to support mental health care for children and adolescents with heart disease include practical screening and access to timely referral and mental health resources., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Despite growing cardiogenic shock (CS) research in adults, the epidemiology, clinical features, and outcomes of children with CS are lacking., Objectives: This study sought to describe the epidemiology, clinical presentation, hospital course, risk factors, and outcomes of CS among children hospitalized for acute decompensated heart failure (ADHF)., Methods: We examined consecutive ADHF hospitalizations (<21 years of age) from a large single-center retrospective cohort. Patients with CS at presentation were analyzed and risk factors for CS and for the primary outcome of in-hospital mortality were identified. A modified Society for Cardiovascular Angiography and Interventions shock classification was created and patients were staged accordingly., Results: A total of 803 hospitalizations for ADHF were identified in 591 unique patients (median age 7.6 years). CS occurred in 207 (26%) hospitalizations. ADHF hospitalizations with CS were characterized by worse systolic function (P = 0.040), higher B-type natriuretic peptide concentration (P = 0.032), and more frequent early severe renal (P = 0.023) and liver (P < 0.001) injury than those without CS. Children presenting in CS received mechanical ventilation (87% vs 26%) and mechanical circulatory support (45% vs 16%) more frequently (both P < 0.001). Analyzing only the most recent ADHF hospitalization, children with CS were at increased risk of in-hospital mortality compared with children without CS (28% vs 11%; OR: 1.91; 95% CI: 1.05-3.45; P = 0.033). Each higher CS stage was associated with greater inpatient mortality (OR: 2.40-8.90; all P < 0.001)., Conclusions: CS occurs in 26% of pediatric hospitalizations for ADHF and is independently associated with hospital mortality. A modified Society for Cardiovascular Angiography and Interventions classification for CS severity showed robust association with increasing mortality., Competing Interests: Funding Support and Author Disclosures Dr Adachi has served as a consultant for Berlin Heart Inc, Medtronic Inc, Jarvik Inc, BiVACOR Inc, and Sony-Olympus Medical Solutions Inc. Dr Price has served as a consultant for American Regent. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Given the numerous opportunities and the wide knowledge gaps in pediatric heart failure, an international group of pediatric heart failure experts with diverse backgrounds were invited and tasked with identifying research gaps in each pediatric heart failure domain that scientists and funding agencies need to focus on over the next decade., Competing Interests: DECLARATION OF COMPETING INTEREST S.A. is a site PI for a multicenter study led by the University of Michigan (reports no salary support). J.H. is the president of the Ohio College of Clinical Pharmacy and reports reimbursement for attending the annual meeting. S.C. reports honoraria for her speaking engagements by Enduring Hearts. J.R. is a consultant for Bayer, Merck, Bristol Myers Squibb, CRI Biotech, and American Regent; and reports payment for medical legal review. J.S. serves on the leadership committee for the Advanced Cardiac Therapies Improving Outcomes Network (ACTION). J.P. is a board member for the myocarditis foundation. S.M. is funded by the NIH/NHLBI, American Heart Association, and Additional Ventures; patents issued: CU2150H (Co-inventor for: “microRNA expression in pediatric heart failure patients), CU2650H (Co-inventor for: “Selective Inhibition of Beta-Adrenergic Receptors for the Treatment of Pediatric Heart Failure), patent pending: CU3250H (Co-inventor for: “microRNAs as a Prognostic Biomarker in Pediatric Heart Failure); and serves on the advisory board for Children's cardiomyopathy foundation, and Additional Ventures. K.L. serves as Chair of the Pediatric heart failure committee, American Heart Association Young Hearts Council. J.C. serves on the DSMB for the PumpKIN and reports unrestricted educational grant from Abbott. M.K.C. receives research funding and salary support from NHLBI (5K23HL145096), reports funding from Additional Ventures and Enduring Hearts, and serves on leadership for ISHLT, Transplant Families, Enduring Hearts. and ACTION. F.Z. reports research funding from National Institutes of Health (R01HL147957) and has stock in TransMedics, Inc. R.S. reports consulting fees from Novartis, CRI Biotech, American Regent, and Rocket Pharmaceuticals. K.S. serves on the scientific advisory board for Enduring Hearts. D.P. serves on the DSMB for Berlin EXCOR Active Driving system study. J.G. reports consulting fees from Daiichi Sankyo and has stock in Abbott. M.C. is funded by NIH/NHLBI, Additional Ventures, and Enduring Hearts. The other authors report no conflicts/disclosures., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The significance of atypical infiltrates (eosinophils or plasma cells) on endomyocardial biopsy (EMB) after pediatric heart transplant (HTx) is not known. We hypothesized that atypical infiltrates are associated with worse post-HTx outcomes., Methods: We performed a retrospective cohort study of consecutive patients <21 years old who underwent primary HTx between 2013 and 2017. Multiorgan transplants were excluded. The presence of atypical infiltrates and burden of atypical infiltrates (rare vs predominant) on EMB were recorded. Primary outcome was a composite of cardiac allograft vasculopathy, graft failure (relisting or retransplant), or death. Presence of atypical infiltrates was evaluated: (1) overall using Cox regression with time-dependent covariates and (2) if present by 1 year post-HTx using Kaplan-Meier analysis., Results: Atypical infiltrates were present in 24 out of 95 patients (25%) and were associated with a higher likelihood of reaching the composite outcome (hazard ratio (HR) 6.22, 95% confidence interval (CI) 2.60-14.89, p < 0.0001). This persisted when controlling for rejection in multivariable analysis. There was also a greater risk of the composite outcome if ≥2 nonconsecutive EMBs had atypical infiltrates (HR 11.80, 95%CI 3.17-43.84, p = 0.0002) or if atypical infiltrates were the predominant feature on EMB (HR 30.58, 95%CI 9.34-100.06, p < 0.0001). Patients with atypical infiltrates by 1-year post-HTx had a 5-year freedom from the composite outcome of 48%, compared to 90% if no atypical infiltrates had been present by this timepoint (log rank p = 0.002)., Conclusions: The presence of atypical infiltrates on EMB is associated with significantly worse outcomes in children following HTx. These patients require closer follow-up to assess for developing graft dysfunction., (Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: We report current outcomes in patients supported with the HeartMate 3 (HM3) ventricular assist device in a multicenter learning network., Methods: The Advanced Cardiac Therapies Improving Outcomes Network database was queried for HM3 implants between 12/2017 and 5/2022. Clinical characteristics, postimplant course, and adverse events were collected. Patients were stratified according to body surface area (BSA) (<1.4 m 2 , 1.4-1.8 m 2 , and >1.8 m 2 ) at device implantation., Results: During the study period, 170 patients were implanted with the HM3 at participating network centers, with median age 15.3years; 27.1% were female. Median BSA was 1.68 m 2 ; the smallest patient was 0.73 m 2 (17.7 kg). Most (71.8%) had a diagnosis of dilated cardiomyopathy. With a median support time of 102.5days, 61.2% underwent transplantation, 22.9% remained supported on device, 7.6% died, and 2.4% underwent device explantation for recovery; the remainder had transferred to another institution or transitioned to a different device type. The most common adverse events included major bleeding (20.8%) and driveline infection (12.9%); ischemic and hemorrhagic stroke were encountered in 6.5% and 1.2% of patients, respectively. Patients with BSA <1.4 m 2 had a higher incidence of infection, renal dysfunction, and ischemic stroke., Conclusions: In this updated cohort of predominantly pediatric patients supported with the HM3 ventricular assist device, outcomes are excellent with <8% mortality on device. Device-related adverse events including stroke, infection, and renal dysfunction were more commonly seen in smaller patients, highlighting opportunities for improvements in care., (Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Although ventricular failure is a late finding in adults with AC, we hypothesize that this is a presenting symptom in pediatric heart failure patients who undergo HT and that their ventricular arrhythmia burden could differentiate AC from other cardiomyopathies., Methods: We performed a single-center retrospective cohort study reviewing 457 consecutive pediatric (≤18 years) HT recipients at our institution. Explanted hearts were examined to establish the primary diagnosis, based on pathologic findings. Demographic and clinical variables were compared between AC versus non-HCM cardiomyopathy cases., Results: Forty-five percent (n = 205/457) had non-HCM cardiomyopathies as the underlying primary diagnosis. Ten cases (10/205 = 4.9%) were diagnosed with AC. All 10 had biventricular disease. In 8/10 patients (80%), AC diagnosis was unrecognized pre-HT. Compared with non-AC cardiomyopathies, the AC group was older at diagnosis (9.3 years vs. 4.3 years, p = .012) and transplant (11.1 years vs. 6.5 years, p = .010), had more ventricular arrhythmias (80.0% vs 32.8%, p = .003), and required more anti-arrhythmic use (80.0% vs 32.3%, p = .001). Genetic testing yielded causative pathogenic variants in all tested individuals (n = 5/5, 100%)., Conclusion: AC is often an unrecognized cardiomyopathy pretransplant in children who undergo HT. Pediatric non-HCM phenotypes with heart failure who have a significant ventricular arrhythmia burden should be investigated for AC., (© 2022 Wiley Periodicals LLC.)

Oral health is vital for the general well-being, overall body health and the quality of life throughout our lifetime. Most of the oral diseases and conditions are largely related to the maintenance of oral hygiene, lacking that people suffer from diverse oral diseases at different times in their life. With greater life expectancy, the individuals have teeth involved with periodontal diseases that would not only require professional care but also home gum care for them to last a lifetime. Indian Society of Periodontology (ISP) has recognized the need for systematic documents to update everyday clinical practice of general dental practitioners and have provided evidence-based consensus documents, namely good clinical practice recommendations from time to time to raise the oral health-related awareness and standards of oral healthcare delivery across the country. The current set of clinical practice recommendations focused to "Gum Care for All", is aimed at emphasizing and enhancing the awareness regarding oral health promotion, maintenance, and disease prevention. Twenty-five subject matter experts from across the nation, prepared these recommendations after a thorough literature review and group discussions. The document has been prepared in three distinct sections, namely pretherapeutic, therapeutic, and post therapeutic, to provide guidance during the respective phases of patient management and may serve as a quick and concise reference to the readers. The guidelines shall provide the distinct definitions, signs and symptoms, treatment required; recall visit specifications for plausible clinical case situations, home care advice regarding maintenance of oral hygiene including information on brushing technique, care and change of brush, use of interdental aids, and mouthwashes, etc. The document should advocate and guide the combined efforts of general dentists, and the population at large toward an empowered, evidence based, integrated, and comprehensive oral health care, which shall enhance the healthful functioning and longevity of the dentition and general health of the individual., (Copyright: © 2023 Indian Society of Periodontology.)

Background: Infants who undergo surgery for congenital heart disease are at risk of neurodevelopmental delay. Cardiac surgery-associated acute kidney injury (CS-AKI) is common but its association with neurodevelopment has not been explored., Methods: This was a single-center retrospective observational study of infants who underwent cardiac surgery in the first year of life who had neurodevelopmental testing using the Bayley Scale for Infant Development, third edition. Single and recurrent episodes of stages 2 and 3 CS-AKI were determined., Results: Of 203 children with median age at first surgery of 12 days, 31% had one or more episodes of severe CS-AKI; of those, 16% had recurrent CS-AKI. Median age at neurodevelopmental assessment was 20 months. The incidence of delay was similar for patients with and patients without CS-AKI but all children with recurrent CS-AKI had a delay in one or more domains and had significantly lower scores in all three domains, namely, cognitive, language, and motor., Conclusions: This study has assessed the association of CS-AKI with neurodevelopmental delay after surgery for congenital heart disease in infancy. Infants who have recurrent CS-AKI in the first year of life are more likely to be delayed and have lower neurodevelopmental scores., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Serum chloride plays an important role in fluid homeostasis and is associated with impaired diuretic responsiveness and mortality in adults with heart failure (HF). We sought to characterize the relationship of serum chloride and diuretic efficiency (DE) and to determine its prognostic importance in children hospitalized with acute decompensated HF (ADHF). We studied DE, defined as net fluid output/kg+constant per mg of loop diuretic/kg, in 200 children hospitalized with ADHF. Median serum chloride at admission was 102 mmol/L (interquartile range 99 to 105 mmol/L), and hypochloremia (chloride ≤96 mmol/L) was present in 16% of the population at admission. Serum chloride correlated with serum sodium (r = 0.66; p < 0.001) and bicarbonate (r = -0.39; p < 0.001). In the adjusted analysis, lower chloride was associated with reduced DE (p < 0.001). Serum sodium was associated with DE on the unadjusted analysis; however, the association was eliminated when added to the model with chloride (p = 0.442). Lower chloride was also associated with features of inadequate decongestion during hospitalization: a positive fluid balance (p = 0.003), greater cumulative loop diuretic dose per weight (p = 0.001), addition of a thiazide diuretic during hospitalization (p < 0.001), less weight loss (p = 0.025), and longer length of stay (p = 0.003). Chloride concentration was independently associated with death or transplant 1 year after admission (hazard ratio 0.94; p < 0.001). As a dichotomous variable, hypochloremia was independently associated with reduced DE (p < 0.001) and decreased 1-year transplant-free survival (hazard ratio 2.3, p < 0.001). Lower serum chloride at hospital admission is strongly and independently associated with impaired DE and reduced transplant-free survival in children hospitalized with ADHF., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Bivalirudin is a direct thrombin inhibitor that is being increasingly used for anticoagulation in children after ventricular assist device (VAD) implantation. While the data on bivalirudin use in pulsatile flow VADs are growing, reports on its use in patients on continuous flow (CF) VAD as well as comparisons of associated outcomes with unfractionated heparin (UFH) remain limited., Design: Retrospective cohort study., Setting: Single tertiary-quaternary referral center., Patients: All patients less than 21 years old on CF-VAD support who received bivalirudin or UFH for anticoagulation between the years 2016 and 2020., Interventions: Not applicable., Measurements and Main Results: Clinical characteristics compared between the cohorts included time to target range of anticoagulation, markers of hemolysis, and prevalence of hemocompatibility-related adverse events such as major hemorrhagic complications, ischemic stroke, and pump thrombosis. In 42 unique patients (41 HeartWare HVAD [Medtronic, Minneapolis, MN], one HeartMate 3 LVAD [Abbott Laboratories, Abbott Park, IL]) during the study period, a total of 67 encounters of IV anticoagulation infusions (29 UFH and 38 bivalirudin) were retrospectively reviewed. In comparison with use of UFH, bivalirudin was associated with lesser odds of major bleeding complications (odds ratio [OR], 0.29; 95% CI, 0.09-0.97; p = 0.038). We failed to identify any difference in odds of major thrombotic complications (OR, 2.53; 95% CI, 0.47-13.59; p = 0.450). Eight of the patients (28%) on UFH were switched to bivalirudin due to hemorrhagic or thrombotic complications or inability to achieve therapeutic anticoagulation, while two of the patients (5%) on bivalirudin were switched to UFH due to hemorrhagic complications. Bivalirudin was used for a "washout" in eight cases with concern for pump thrombosis-six had resolution of the pump thrombosis, while two needed pump exchange., Conclusions: Use of bivalirudin for anticoagulation in patients on CF-VAD support was associated with lesser odds of hemorrhagic complications compared with use of UFH. Bivalirudin "washout" was successful in medical management of six of eight cases of possible pump thrombosis., Competing Interests: Drs. Puri, Tunuguntla, Spinner, and Adachi disclosed the off-label product use of HeartWare HVAD for ventricular assist device support. Drs. Puri, Tunuguntla, Hensch, and Teruya disclosed the off-label product use of bivalirudin for first-line anticoagulation. Dr. Adachi reported consultant/proctor for Berlin Heart, Medtronic, Abbott, Abiomed, Jarvik, BiVACOR, and Sony-Olympus Medical Solutions. Dr. Teruya received funding from Hemosonics and UptoDate. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: Interleukin-1β (IL-1β) is one of the most important cytokines that seems to have an important role in the inflammatory process in gingival and peri-implant tissues. As peri-implant crevicular fluid (PICF) provides with a more swift and objective measure of the disease activity, the present study was conducted to evaluate IL-1β level in PICF as a biochemical marker and to investigate its correlation with clinical parameters and radiological parameters., Materials and Methods: After evaluating all the patients following inclusion and exclusion criteria, 60 patients were selected for the study. After 3-4 months of implants placement, the implants were exposed following standard surgical procedure. PICF sample from implant site was taken 3 days after suture removal with gingival former still in place followed by measurement of clinical and radiological parameters., Results: There was significant increase in IL-1β levels in both the follow-ups from baseline with variable and minimal change in the clinical parameters and radiological parameters as well, which shows that IL-1β levels change significantly even when there is a minimal gingival inflammation., Conclusion: Therefore, IL-1β level in PICF can be used as an adjunctive diagnostic marker to clinical and radiographic parameters for assessing the peri-implant health status., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 National Journal of Maxillofacial Surgery.)

A 3-year-old boy presented with episodes of uneasiness and transient loss of consciousness. Atrial tachyarrhythmias with rapid ventricular rate was diagnosed and initially unsuccessfully treated with oral antiarrhythmic drugs. Subsequent Holter monitoring revealed ventricular arrhythmias. Despite pharmacologic treatment, he needed numerous cardioversions. Surgical sympathectomy was planned. Initially, sympathectomy was achieved using a continuous high thoracic epidural block and was performed to ascertain the efficacy of the thoracic sympathectomy. This successfully reduced the ventricular arrhythmias and the need for antiarrhythmic agents. The epidural infusion was also used for pain relief following the subsequent surgical sympathectomy., (© 2022 John Wiley & Sons Ltd.)

Data are limited regarding body mass index (BMI) in pediatric patients supported by ventricular assist devices (VAD) and associated clinical outcomes and complications. We performed a retrospective single-center cohort study including patients aged ≤21 years on durable continuous-flow VAD support for ≥30 days from 2009 to 2020. Patients were classified based on BMI percentile at implant using the US Centers for Disease Control and Prevention criteria: underweight (<5th percentile), healthy weight (5th-<85th percentile, reference group), overweight (85th-<95th percentile), and obese (≥95th percentile). Primary outcomes were hospital mortality and length of stay (LOS) after implant. Secondary outcomes included infectious complications and pump thrombosis. Seventy-two patients (58 HeartWare, 13 HeartMateII, 1 HeartMate3) were included. At implant, the study cohort comprised 13% underweight, 53% healthy weight, 18% overweight, and 17% obese. BMI increased across all categories during support, with 29% gaining BMI categories. No patients with obesity reduced their BMI category. At explant, the study cohort comprised 1% underweight, 54% healthy weight, 22% overweight, and 22% obese. There was no significant difference in hospital mortality, postoperative LOS, or pump thrombosis. Patients who were overweight had more frequent non-VAD infections. Patients with obesity required longer duration on VAD support and were less likely to be transplanted. We concluded that pediatric patients on VAD support who are overweight or have obesity do not improve their BMI and instead have significant increase. Larger studies are needed to assess the impact of abnormal BMI on VAD complications in pediatric patients., Competing Interests: Dr Adachi reported consultant/proctor for Berlin Heart Inc, Medtronic Inc, Abbott Inc, Jarvik Inc, BiVACOR Inc, and Sony-Olympus Medical Solutions, Inc. The remaining authors have no conflicts of interest or financial disclosures relevant to this article to disclose., (Copyright © ASAIO 2021.)

Oxygen saturation is the percentage of hemoglobin that is saturated with oxygen, converting it to oxyhemoglobin. Oxygen saturation is a critical part of the physical examination of children with congenital heart disease (CHD). The expected oxygen saturation of a patient with CHD depends on their anatomical lesion, their previous surgeries, and any additional pulmonary or systemic pathology that may derange their saturation. Oxygen saturation can be noninvasively measured using pulse oximetry. Pulse oximetry is based on the differential absorption of infrared and red light by oxyhemoglobin and deoxyhemoglobin, with the former absorbing more infrared than the latter. Pulse oximetry readings may be inaccurate in settings of low cardiac output, peripheral vasoconstriction, arrhythmia, hypothermia, and venous pulsations. The use of pulse oximetry in the care of a child with CHD begins with the newborn critical CHD screen. A failed screen indicates a need for further investigation, such as repeated pulse oximetry or echocardiography. The oxyhemoglobin dissociation curve may be used to estimate the partial pressure of oxygen in the blood at various oxygen saturations. It is also a marker of the affinity of hemoglobin for oxygen, with a right-shifted curve indicating a higher oxygen tension needed to saturate hemoglobin. This is a helpful adaptation of the body to situations of stress such as fever, acidosis, and hypercapnia. An understanding of these concepts is paramount for providers caring for patients with known or potential CHD in any setting to appropriately interpret and respond to abnormal saturations for each child., (© American Academy of Pediatrics, 2022. All rights reserved.)

Introduction: Iron deficiency is associated with worse outcomes in children and adults with systolic heart failure. While oral iron replacement has been shown to be ineffective in adults with heart failure, its efficacy in children with heart failure is unknown. We hypothesised that oral iron would be ineffective in replenishing iron stores in ≥50% of children with heart failure., Methods: We performed a single-centre retrospective cohort study of patients aged ≤21 years with systolic heart failure and iron deficiency who received oral iron between 01/2013 and 04/2019. Iron deficiency was defined as ≥2 of the following: serum iron <50 mcg/dL, serum ferritin <20 ng/mL, transferrin >300 ng/mL, transferrin saturation <15%. Iron studies and haematologic indices pre- and post-iron therapy were compared using paired-samples Wilcoxon test., Results: Fifty-one children with systolic heart failure and iron deficiency (median age 11 years, 49% female) met inclusion criteria. Heart failure aetiologies included cardiomyopathy (51%), congenital heart disease (37%), and history of heart transplantation with graft dysfunction (12%). Median dose of oral iron therapy was 2.9 mg/kg/day of elemental iron, prescribed for a median duration of 96 days. Follow-up iron testing was available for 20 patients, of whom 55% (11/20) remained iron deficient despite oral iron therapy., Conclusions: This is the first report on the efficacy of oral iron therapy in children with heart failure. Over half of the children with heart failure did not respond to oral iron and remained iron deficient.

Background: Guidance and data on ventricular assist device (VAD) support for children with chemotherapy-induced cardiomyopathy, particularly within the first 2 years after chemotherapy, are limited., Methods: We performed a single-center retrospective case series, reviewing medical records of children <18 years of age with chemotherapy-induced cardiomyopathy and advanced heart failure (HF) who received durable VAD support., Results: Six patients met inclusion criteria-5 HeartWare™ HVAD, 1 Berlin Heart EXCOR ® . Median age at cancer diagnosis was 6 years (IQR 4.5-10 years). Median dose of anthracycline received was 540 mg/m 2 (IQR 450-630 mg/m 2 ). All patients developed HF within 1 year after initiation of cancer treatment (median 8 months, IQR 6-11.5 months) and were initiated on durable VAD support at a median of 8 months after completion of cancer treatment (IQR 3.3-43.5 months). Four patients had significant right ventricular dysfunction needing oral pulmonary vasodilator therapy, one patient had a major bleeding complication, and two patients had thromboembolic strokes while on VAD support. Median duration of VAD support was 7.5 months (IQR 3-11.3 months). Two patients underwent VAD explant due to recovery of LV function, one died due to cancer progression, and three underwent heart transplantation., Conclusions: Durable VAD support should be considered as a therapeutic option for children who have advanced HF due to chemotherapy-induced cardiomyopathy, even within 2 years of completing cancer treatment. A multi-disciplinary approach is essential for appropriate patient selection prior to implant and to ensure comprehensive care throughout the duration of VAD support., (© 2022 Wiley Periodicals LLC.)

Formation of black triangles due to the loss of interdental papilla is one of the utmost perplexing esthetic problems of the periodontium. Many surgical and nonsurgical treatment options have been researched upon to obtain complete papillary fill, but minimally invasive procedures have always been the choice of treatment both for the operator as well as the patient. This article describes the use of injectable platelet-rich fibrin (i-PRF) as a novel nonsurgical technique for the reconstruction of deficient interdental papilla. This is probably the first article that describes the use of i-PRF for the nonsurgical treatment of black triangles. Six sites with the presence of deficient interdental papilla in four patients were selected for this case series. After completion and reevaluation of scaling and root planing, autologous i-PRF was injected at the base of the interdental papilla using the insulin syringe. Photographs obtained before the treatment and at 1, 3, and 6 months after the intervention were assessed by Image J software along with clinical measurements. The use of novel nonsurgical injectable PRF technique allows clinician to successfully treat deficient interdental papilla., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Society of Periodontology.)

Objectives: To investigate the prevalence of left ventricular systolic dysfunction (LVSD) in Malawian children with severe febrile illness and to explore associations between LVSD and mortality and lactate levels., Design: Prospective observational study., Setting: Pediatric ward of a tertiary government referral hospital in Malawi., Patients: Children between 60 days and 10 years old with severe febrile illness (fever with at least one sign of impaired perfusion plus altered mentation or respiratory distress) were enrolled at admission from October 2017 to February 2018., Interventions: Focused cardiac ultrasound (FoCUS) was performed, and serum lactate was measured for each child at enrollment, with repeat FoCUS the following day. LV systolic function was later categorized as normal, reduced, severely reduced, or hyperdynamic by two pediatric cardiologists blinded to clinical course and outcomes., Measurements and Main Results: Fifty-four children were enrolled. LVSD was present in 14 children (25.9%; 95% CI, 15.4-40.3%), of whom three had severely reduced function. Thirty patients (60%) had a lactate greater than 2.5 mmol/L, of which 20 (40%) were markedly elevated (>5 mmol/L). Ten children died during admission (18.5%). Of children who survived, 22.7% had decreased LV systolic function versus 40% of those who died. Dysfunction was not associated with mortality or elevated lactate., Conclusions: Cardiac dysfunction may be present in one in four Malawian children with severe febrile illness, and mortality in these patients is especially high. Larger studies are needed to further clarify the role cardiac dysfunction plays in mortality and integrate practical bedside assessments for decision support around individualized resuscitation strategies., Competing Interests: Dr. Mkaliainga received funding from the Cincinnati Children’s Hospital Medical Center Division of Emergency Medicine. Dr. Banda’s institution received funding from a divisional small grant from Cincinnati Children’s Hospital Medical Center. Dr. Byczkowski disclosed that she taught a fellow class on statistical process control at Seattle Children’s Hospital. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Herein we report the first total syntheses of the trisaccharide-repeating units of Pseudomonas chlororaphis subsp. aureofaciens UCM B-306 via a one-pot assembly of the core trisaccharide structure. The rare-sugar-containing trisaccharide-repeating units are comprised of d-bacillosamine, 2-amino-2-deoxy-d-galacturonic acid or amide, and d-rhamnose units linked through three consecutive α-linkages. The total syntheses of two repeating units were completed starting from d-mannose via a longest-linear sequence of 27 steps in 5.8% and 4.4% overall yields, respectively.

Background: Valvular disease in pediatric and young adult donor hearts may be a relative contraindication to graft use. Outcomes following the use of donor hearts with bicuspid aortic valve (BAV) have not been previously reported in children. We describe 4 cases of pediatric heart transplantation (HTx) utilizing a donor heart with a BAV., Case Series: Of the 469 HTx included in this study, 4 utilized a donor heart with a BAV. All recipients were female; median age was 11 years (range 0.3 to 19 years). In all cases, the BAV was not discovered until after HTx. All donors were less than 30 years old. The patients were followed for a median of 6 years (range 2 to 9 years) with all patients alive at last follow-up. Two patients have transitioned to adult care, and 2 patients continue to follow in our clinic. In follow-up, no patient has required an aortic valve intervention or had infective endocarditis. At last review, no patient had greater than mild aortic insufficiency or more than mild aortic stenosis. Three patients developed mild-to-moderate left ventricular hypertrophy in the first year post-transplant that improved over time. One patient experienced a peri-operative embolic stroke at time of transplant unrelated to the BAV., Conclusion: On short- and intermediate-term follow-up, pediatric and young adult donor hearts with BAV demonstrated acceptable graft longevity and valvular function. A functionally normal BAV in a pediatric heart transplant donor should not be a contraindication to organ acceptance., (© 2021 Wiley Periodicals LLC.)

Context: Optimum preoperative fasting is imperative for the prevention of aspiration in pediatric patients. The current guidelines advocate 2-4-6 rule for the same. However, direct supervision is lacking in large volume centers., Aims: Thus, we aimed to determine the fasting compliance of children preoperatively and to ascertain whether parents understood the significance and purpose of optimum fasting., Materials and Methods: Design - A prospective questionnaire-based study regarding preoperative fasting was performed in pediatric patients aged 1-10 years scheduled for "day care surgery" or "same day admission surgery" over 12 weeks. Thereafter, parental awareness drive was carried out, and a re-audit was performed with a questionnaire in the next cohort of patients., Results: The number of patients in the pre and postcounseling groups were 98 and 99. Thirteen percent of the patients were optimally fasted for solids initially. Re-audit confirmed compliance increased to 46%. Patients fasting adequately (2-3 h) for clear fluids increased from 22.4% to 51.5% postcounseling. The number for optimally breast-fed children increased postaudit (23.1%-39.1%). Consequent to the drive, parental awareness increased and 49.5% parents knew that only plain water was permitted during fasting. Number of parents considering preoperative fasting important increased from 39.8% to 79.7%. Initially, 27.6% of the parents did not know the reason for fasting, which reduced to 3% postaudit., Conclusion: Parents are misinformed and ignorant about optimum preoperative fasting. Adequate education and awareness to improve their knowledge was associated with increased compliance for optimal fasting., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Indian Association of Pediatric Surgeons.)

Cardiac muscle uses multiple sources of energy including glucose and fatty acid (FA). The heart cannot synthesize FA and relies on obtaining it from other sources, with lipoprotein lipase (LPL) breakdown of lipoproteins suggested to be a key source of FA for cardiac use. Recent work has indicated that cardiac vascular endothelial growth factor B (VEGFB) overexpression expands the coronary vasculature and facilitates metabolic reprogramming that favors glucose utilization. We wanted to explore whether this influence of VEGFB on cardiac metabolism involves regulation of LPL activity with consequent effects on lipotoxicity and insulin signaling. The transcriptomes of rats with and without cardiomyocyte-specific overexpression of human VEGFB were compared by using RNA sequencing. Isolated perfused hearts or cardiomyocytes incubated with heparin were used to enable measurement of LPL activity. Untargeted metabolomic analysis was performed for quantification of cardiac lipid metabolites. Cardiac insulin sensitivity was evaluated using fast-acting insulin. Isolated heart and cardiomyocytes were used to determine transgene-encoded VEGFB isoform secretion patterns and mitochondrial oxidative capacity using high-resolution respirometry and extracellular flux analysis. In vitro, transgenic cardiomyocytes incubated overnight and thus exposed to abundantly secreted VEGFB isoforms, in the absence of any in vivo confounding regulators of cardiac metabolism, demonstrated higher basal oxygen consumption. In the whole heart, VEGFB overexpression induced an angiogenic response that was accompanied by limited cardiac LPL activity through multiple mechanisms. This was associated with a lowered accumulation of lipid intermediates, diacylglycerols and lysophosphatidylcholine, that are known to influence insulin action. In response to exogenous insulin, transgenic hearts demonstrated increased insulin sensitivity. In conclusion, the interrogation of VEGFB function on cardiac metabolism uncovered an intriguing and previously unappreciated effect to lower LPL activity and prevent lipid metabolite accumulation to improve insulin action. VEGFB could be a potential cardioprotective therapy to treat metabolic disorders, for example, diabetes. NEW & NOTEWORTHY In hearts overexpressing vascular endothelial growth factor B (VEGFB), besides its known angiogenic response, multiple regulatory mechanisms lowered coronary LPL. This was accompanied by limited cardiac lipid metabolite accumulation with an augmentation of cardiac insulin action. Our data for the first time links VEGFB to coronary LPL in regulation of cardiac metabolism. VEGFB may be cardioprotective in metabolic disorders like diabetes.

Competing Interests: Dr. Adachi received funding from Abbott, Medtronic, Abiomed, Berlin Heart, Jarvik, BiVACOR, and Sony-Olympus Medical Solutions. Dr. Puri has disclosed that she does not have any potential conflicts of interest.

The evolution of cancer therapies has led to marked improvement in survival of those affected by childhood malignancies, while also increasing the recognition of early and late toxicities associated with cancer therapies. Cardiotoxicity can include cardiomyopathy/heart failure, coronary artery disease, stroke, pericardial disease, arrhythmias, and valvular and vascular dysfunction as a result of exposure to chemotherapy and/or radiation. Anthracyclines remain the most common cause of chemotherapy-induced cardiomyopathy (CCM) with varying clinical presentations including: acute, early onset, and late-onset. Many individuals develop cardiac dysfunction over the long-term, ranging from subclinical cardiac dysfunction to end-stage symptomatic heart failure. The focus of this review is on characterization of symptomatic heart failure in children with cancer therapy-related cardiac dysfunction (CTRCD) primarily due to CCM and utilization of advanced heart failure therapies, including ventricular assist device (VAD) support and heart transplantation, with consideration of unique patient-related factors.

Herein, we report the total synthesis of the phosphorylated zwitterionic trisaccharide repeating unit of Photorhabdus temperata subsp. cinerea 3240. The efficient route involves regio- and stereoselective assembly of trisaccharide with rare deoxyamino sugar AAT at the nonreducing end, late stage oxidation, and installation of a phosphate linker on the trisaccharide. The total synthesis was completed via a longest linear sequence of 24 steps in 6.5% overall yield.

Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported.

Patients with perinatal and neonatal congenital heart disease (CHD) represent a unique population with higher morbidity and mortality compared to other neonatal patient groups. Despite an overall improvement in long-term survival, they often require chronic care of complex medical illnesses after hospital discharge, placing a high burden of responsibility on their families. Emerging literature reflects high levels of depression and anxiety which plague parents, starting as early as the time of prenatal diagnosis. In the current era of the global COVID-19 pandemic, the additive nature of significant stressors for both medical providers and families can have catastrophic consequences on communication and coping. Due to the high prognostic uncertainty of CHD, data suggests that early pediatric palliative care (PC) consultation may improve shared decision-making, communication, and coping, while minimizing unnecessary medical interventions. However, barriers to pediatric PC persist largely due to the perception that PC consultation is indicative of "giving up." This review serves to highlight the evolving landscape of perinatal and neonatal CHD and the need for earlier and longitudinal integration of pediatric PC in order to provide high-quality, interdisciplinary care to patients and families.

Heart failure is a life-changing diagnosis for a child and their family. Pediatric patients with heart failure experience significant morbidity and frequent hospitalizations, and many require advanced therapies such as mechanical circulatory support and/or heart transplantation. Pediatric palliative care is an integral resource for the care of patients with heart failure along its continuum. This includes support during the grief of a new diagnosis in a child critically ill with decompensated heart failure, discussion of goals of care and the complexities of mechanical circulatory support, the pensive wait for heart transplantation, and symptom management and psychosocial support throughout the journey. In this article, we discuss the scope of pediatric palliative care in the realm of pediatric heart failure, ventricular assist device (VAD) support, and heart transplantation. We review the limited, albeit growing, literature in this field, with an added focus on difficult conversation and decision support surrounding re-transplantation, HF in young adults with congenital heart disease, the possibility of destination therapy VAD, and the grimmest decision of VAD de-activation.

Tracheostomy is associated with increased mortality and resource utilization in children with CHD. However, the prevalence and hospital outcomes of tracheostomy in children with HTx are not known. We describe the prevalence and compare the post-HTx hospital outcomes of pediatric patients with Pre-TT and Post-TT to those without tracheostomy. A multi-institutional retrospective cohort study was performed using the Pediatric Health Information System database. Hospital mortality, mediastinitis, LOS, and costs were compared among patients with Pre-TT, Post-TT, and no tracheostomy. Pre-TT was identified in 29 (1.1%) and Post-TT was identified in 41 (1.6%) of 2603 index HTx hospitalizations. Patients with Pre-TT were younger and more likely to have CHD, a non-cardiac birth defect, or an airway anomaly compared to those without Pre-TT. Pre-TT was not independently associated with increased post-HTx in-hospital mortality. Age at HTx < 1 year, CHD, and Post-TT were associated with increased in-hospital mortality. Pre-TT that occurred during the HTx hospitalization and Post-TT were associated with increased resource utilization. Tracheostomy was not associated with mediastinitis., (© 2020 Wiley Periodicals LLC.)

Competing Interests: POTENTIAL CONFLICT OF INTEREST: Drs First and Kemper are editors of Pediatrics; and Dr Puri has indicated she has no potential conflicts of interest to disclose.

With the substantial growth of pediatric ventricular assist device (VAD) support, there has been an expansion of the target population towards more complex patients, including congenital heart disease (CHD) with single ventricle (SV) physiology. The outcomes of Stage I and Stage II SV-CHD patients on VAD support from the Pedimacs database are poor, with less than 50% survival on VAD by the 3-month mark in both. The primary objective of this article is to describe the current state of VAD support for the failing Stage I and II SV-CHD circulation, to provide insight into potential areas of outcome improvement. We reviewed the published literature in the form of database and registry reports as well as single-center studies to discuss the outcomes of Stage I and Stage II SV-CHD patients on VAD support. Registry-based studies suggest that VAD support for the failing Stage I and Stage II SV-CHD circulations is challenging. However, the more promising outcomes in several single-institutional reports for both Stage I and Stage II SV-VAD indicate that the grim picture from the databases does not reflect the best outcomes that are possible to be achieved, potentially at experienced centers with higher volumes. Areas of future study and potential improvement including timely initiation of VAD support in the cohort of patients expected to not be a candidate for standard SV palliations, pump selection and the benefits of continuous-flow devices, and the decision-making for setting up the optimum circulation for VAD support, be it Fontan completion if feasible or takedown to shunt physiology., (Copyright © 2021. Published by Elsevier Inc.)

Autoimmune pancreatitis (AIP) is a chronic inflammatory condition rarely reported in children. In 2018, to standardize the approach to AIP, INternational Study Group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE) defined AIP, outlined the clinical course, and developed diagnostic and therapeutic recommendations. We performed a retrospective review of cases at our institution from January 1, 2016, to June 1, 2019, and compared their presentations with the INSPPIRE guidelines. Our patients showed variable laboratory, radiographic, and histologic findings, highlighting the difficulty in diagnosing AIP. Histologic samples were obtained in our patients due to diagnostic uncertainty, which ultimately confirmed the diagnosis. One patient was diagnosed with autoimmune hepatitis coexistent with AIP, which has not been previously described in the pediatric population. Exocrine and endocrine complications of AIP were also noted. In all cases, symptoms improved following treatment, and decompression of the common bile duct was seen on repeat imaging., (Copyright © 2020 The Author(s). Published by Wolters Kluwer on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Fungal infections are a global issue affecting over 150 million people worldwide annually, with 750 000 of these caused by invasive Candida infections. Azole drugs are the frontline treatment against fungal infections; however, resistance to current azole antifungals in C. albicans poses a threat to public health. Two series of novel azole derivatives, short and extended derivatives, have been designed, synthesised and investigated for CYP51 inhibitory activity, binding affinity and minimum inhibitory concentration (MIC) against C. albicans strains. The short derivatives were more potent against the C. albicans strains (e. g., MIC 2-(4-chlorophenyl)-N-(2,4-dichlorobenzyl)-3-(1H-imidazol-1-yl)propanamide (5 f) <0.03 μg/mL, N-(4-((4-chlorophenyl)sulfonamido)benzyl)-2-phenyl-3-(1H-1,2,4-triazol-1-yl)propanamide (12 c), 1 μg/mL, fluconazole 0.125 μg/mL) but both displayed comparable enzyme binding and inhibition (5 f K d 62±17 nM, IC 50 0.46 μM; 12 c K d 43±18 nM, IC 50 0.33 μM, fluconazole K d 41±13 nM, IC 50 0.31 μM, posaconazole K d 43±11 nM, IC 50 0.2 μM). The short series had poor selectivity for CaCYP51 over the human homologue, whereas the selectivity of the extended series, for example, compound 12 c, was higher (21.5-fold) than posaconazole (4.7-fold) based on K d values, although posaconazole was more selective (615-fold) than 12 c (461-fold) based on IC 50 values. Based on inhibitory activity and selectivity profile, the extended series are the better of the two series for further development., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Platypnea-orthodeoxia means low oxygen saturation and dyspnea in the upright posture which improves on lying down. The causes can be classified into the intrapulmonary shunt, intracardiac shunt, and ventilation-perfusion mismatch. A 62-year-old male presented with shortness of breath, which had worsened over a period of one year. Various investigations were done to rule bacterial, viral infection, pulmonary embolism, and other respiratory and cardiac causes. The initial echocardiogram showed an ejection fraction of 55%. The patient was observed to be having dyspnea only in the upright position. In the recumbent position, the dyspnea disappeared with a marked improvement in oxygen saturation. A repeat echocardiogram with a bubble study was done which showed an atrial septal defect. Surgical closure of the defect was performed which improved the patient's oxygen saturation to baseline normal. This case demonstrates that a vigilant approach is required in cases of dyspnea, keeping in mind the not-so-common phenomenon like platypnea-orthodeoxia syndrome., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Puri et al.)

Background: Blood component mistransfusion is generally due to preventable clerical errors, specifically pretransfusion misidentification of patient/blood unit at bedside. Hence, electronic devices such as barcode scanners are recommended as the standard instrument used to check the patient's identity. However, several healthcare facilities in underdeveloped countries cannot afford this instrument; hence, they usually perform subjective visual assessment to check the patient's identity. This type of assessment is prone to clinical errors, which precipitates significant level of anxiety in the healthcare personnel transfusing the blood unit. Hence, a novel objective method in performing pretransfusion identity check, the 'Sandesh Positive-Negative (SPON) protocol,' was developed., Methods: A nonrandomized study on bedside pretransfusion identity check was conducted, and 75 health care personnel performed transfusion. The intervention was performed by matching a custom-made negative label with blood component with the positive label of the same patient available at bedside who was about to receive transfusion., Results: In total, 85.3% of the subjects were anxious while performing pretransfusion identity check based on the existing standard practice. After the implementation of the SPON protocol, only 38.7% experienced either mild, moderate or severe anxiety. The overall level of satisfaction also increased from 8.0% to 38.7% and none were dissatisfied. Although only 9.3% were dissatisfied about the existing practice, approximately 70.7% felt the need for a better/additional protocol. Clerical error was not observed., Conclusions: The SPON protocol is a cost-effective objective method that reduces anxiety and increases satisfaction levels when performing final bedside identity check of blood components.

Traditionally, the management of diabetes has focused mainly on controlling high blood glucose levels. Unfortunately, despite valiant efforts to normalize this blood glucose, poor medication management predisposes these patients to heart failure. Following diabetes, how the heart utilizes different sources of fuel for energy is key to the development of heart failure. The diabetic heart switches from using both glucose and fats, to predominately using fats as an energy resource for maintaining its activities. This transformation to using fats as an exclusive source of energy is helpful in the initial stages of the disease and is tightly controlled. However, over the progression of diabetes, there is a loss of this controlled supply and use of fats, which ultimately has terrible consequences since the uncontrolled use of fats produces toxic by-products which weaken heart function and cause heart disease. Heparanase is a key player that directs how much fats are provided to the heart and does so in association with several partners like LPL and VEGFs. Together, they regulate the amount of fats supplied, and their subsequent breakdown to provide energy. Following diabetes, there is a disruption in this network resulting in fat oversupply and cell death. Understanding how the heparanase-LPL-VEGFs "ensemble" cooperates, and its dysfunction in the diabetic heart would be useful in restoring metabolic equilibrium and limiting diabetes-related cardiac damage.

Background: Effusion cytology is a major diagnostic tool in medicine and has both therapeutic and prognostic implications. One of the dilemmas encountered is the differentiation between atypical cells and reactive mesothelial cells. The use of ancillary tools can reduce this grey zone and help to achieve a definitive diagnosis., Objectives: The main objective of this study was to evaluate the role of flow cytometry (FCM) and cell block with immunohistochemistry (IHC), along with the clinicoradiological investigations, to achieve a final diagnosis in effusion cytology to the maximum extent possible., Method: A prospective study was conducted. Effusion fluids, showing adequate amount and cellularity, were processed for conventional cytology, ploidy analysis by FCM, and cell block analysis, followed by IHC wherever required. Conventional cytological analysis was done by 2 independent pathologists, to look for interobserver variation, if any. The final result was achieved on the basis of integration of the results of the aforementioned studies, cytological details, clinicoradiological information, tissue biopsy findings, and follow-up., Result: A total of 90 samples were analyzed. On cytological examination, observer I categorized 60% samples as benign and 18.8% (n = 17) as malignant versus 58% categorized as benign and 23.3% (n = 21) as malignant by observer II. Observer I reported 19 (21.1%) equivocal cases and observer II reported 16 (17.7%). When both pathologists were considered together, the number of equivocal cases increased to 20. Sensitivity and specificity of FCM were 96.67 and 100%, respectively, and 100% for the cell block. On combining all techniques, the equivocal cases were resolved and a total of 33 cases were reported as malignant. However, 3 cases could still not be categorized and were labeled inconclusive., Conclusion: Conventional cytology combined with cell block IHC and FCM has the potential to minimize the requirement of tissue biopsy for confirmation. If the first sample is used judiciously for all the techniques, this may reduce the requirement for a second sample and possibly also the time required for a definite diagnosis and the initiation of therapy., (© 2019 S. Karger AG, Basel.)

Objective: To evaluate the prevalence of iron deficiency and its association with outcomes in children with heart failure., Study Design: A single-center retrospective cohort study of patients with heart failure aged 1-21 years from July 2012 to June 2017 with available serum iron studies was performed. Subjects were analyzed in 2 groups: biventricular systolic heart failure (BiV) and single-ventricle congenital heart disease with systolic heart failure (SV). Iron deficiency was defined as ≥2 of the following: serum iron <50 μg/dL, serum ferritin <20 ng/mL, transferrin >300 ng/mL, or transferrin saturation <15%. The primary outcome was a composite adverse event (CAE) of ventricular assist device implantation, heart transplantation, or death, at 3 and 6 months from time of iron studies., Results: Of the 107 subjects (77 BiV, 30 SV) included in the study, 56% were iron deficient. Demographics, etiology of heart failure, and chronicity of heart failure symptoms were not associated with iron deficiency. On multivariable analysis, in group BiV, iron deficiency was associated with CAE at 3 months (79% iron deficiency in CAE group vs 37% iron deficiency in non-CAE, P = .001, OR 7, 95% CI 2-21) and 6 months (76% iron deficiency in CAE vs 35% iron deficiency in non-CAE, P = .002, OR 7, 95% CI 2-24). In group SV, iron deficiency was associated with CAE at 6 months (79% iron deficiency in CAE vs 29% iron deficiency in non-CAE, P = .014, OR 8, 95% CI 2-32)., Conclusions: Iron deficiency was present in 56% of the pediatric patients with heart failure who were evaluated with iron studies. Iron deficiency was associated with greater risk of ventricular assist device implantation, heart transplantation, or death., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background Fatty acid (FA) provision to the heart is from cardiomyocyte and adipose depots, plus lipoprotein lipase action. We tested how a graded reduction in insulin impacts the source of FA used by cardiomyocytes and the cardiac adaptations required to process these FA. Methods and Results Rats injected with 55 (D55) or 100 (D100) mg/kg streptozotocin were terminated after 4 days. Although D55 and D100 were equally hyperglycemic, D100 showed markedly lower pancreatic and plasma insulin and loss of lipoprotein lipase, which in D55 hearts had expanded. There was minimal change in plasma FA in D55. However, D100 exhibited a 2- to 3-fold increase in various saturated, monounsaturated, and polyunsaturated FA in the plasma. D100 demonstrated dramatic cardiac transcriptomic changes with 1574 genes differentially expressed compared with only 49 in D55. Augmented mitochondrial and peroxisomal β-oxidation in D100 was not matched by elevated tricarboxylic acid or oxidative phosphorylation. With increasing FA, although control myocytes responded by augmenting basal respiration, this was minimized in D55 and reversed in D100. Metabolomic profiling identified significant lipid accumulation in D100 hearts, which also exhibited sizeable change in genes related to apoptosis and terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells. Conclusions With increasing severity of diabetes mellitus, when the diabetic heart is unable to control its own FA supply using lipoprotein lipase, it undergoes dramatic reprogramming that is linked to handling of excess FA that arise from adipose tissue. This transition results in a cardiac metabolic signature that embraces mitochondrial FA overload, oxidative stress, triglyceride storage, and cell death.

Background: The palatal donor site of the free gingival graft (FGG) significantly influences the pain and discomfort experienced by the patient, and there is a potential for postoperative bleeding. The aim of this study was to compare the wound healing parameters with the use of a commercially available collagen dressing (CollaCote ® ) and platelet-rich fibrin (PRF) membrane as palatal bandage., Materials and Methods: Twenty patients requiring FGG either for reduced/inadequate gingiva or gingival recession in the maxillary or mandibular anterior region were divided into two groups. In the first experimental group (10 patients), CollaCote ® membrane was placed over the palatal wounds; conversely, the second experimental group patients were treated with a PRF membrane as palatal bandage. Clinical parameters recorded includes depth, immediate, and delayed bleeding, size of wound, pain, and tests for epithelialization which included hydrogen peroxide test and toluidine blue test at various time intervals., Results: Intragroup comparisons showed significant improvement in wound healing parameters in both the groups. No statistically significant difference was found on intergroup comparison with respect to depth, hemorrhage, pain, epithelialization, and size, though the PRF group healed slightly better initially., Conclusion: Both CollaCote ® and PRF palatal bandages significantly accelerate palatal wound healing and reduce the patient's pain and discomfort. PRF was easier to handle and suture and is also autogenous and economical as compared to CollaCote ® ., Competing Interests: None