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BackgroundSepsis is a syndromic response to infection that carries a significant global health burden, with 11 million deaths reported globally in 2017. Many biomarkers have been developed over the years for early identification and prognosis in patients with sepsis. However, they lack the sensitivity and specificity for routine use in clinical practice. A significant challenge in developing a sepsis biomarker has been the lack of a robust pathobiological framework: a factor with a weak immunological basis to assess therapeutic efficacy. The transcript can aid in extrapolating immunological changes to the clinical arena. Given that transcriptomic processing forms a part of a systems biology analysis, we undertook to address the question:What is known about the relationship of the transcript to clinical sepsis?ObjectiveConsequently, this review article envisages a systems-based approach to better understand sepsis using mRNA gene expression information. This was achieved through an examination of peer-reviewed literature identifying the relationship of the transcript to clinical sepsis.MethodsInformation sources included peer-reviewed PubMed-indexed journals using the PubMed database. To be eligible, articles specific to sepsis were selected, being published between the years 2012 to 2022 inclusive. A content analysis of findings was conducted.ResultsThe search strategy elicited 14,048 studies. Keywords and or mesh terms were applied as single terms or Boolean string search combinations, generating 36 studies. Literature was analyzed concerning the specific use of the transcript and its application to sepsis. Five main descriptive Sepsis categories were identified: (1) Definition; (2) Classification; (3) Severity, (4) Molecular Biomarkers, and (5) Benchmarking.ConclusionsEvidence of the connection of the transcript to clinical sepsis was identified. This provided a systems perspective, interfacing transcriptomic data to parameters important in the clinical arena. The use of transcriptomic data in advancing patient sepsis care, thereby aiming to improve precision, requires further investigation.

Diastolic dysfunction (DD) refers to abnormalities in the mechanical function of the left ventricle (LV) during diastole. Severe LVDD can cause symptoms and the signs of heart failure (HF) in the setting of normal or near normal LV systolic function and is referred to as diastolic HF or HF with preserved ejection fraction (HFpEF). Pediatric cardiologists have long speculated HFpEF in children with congenital heart disease and cardiomyopathy. However, understanding the risk factors, clinical course, and validated biomarkers predictive of the outcome of HFpEF in children is challenging due to heterogeneous etiologies and overlapping pathophysiological mechanisms. The natural history of HFpEF varies depending upon the patient's age, sex, race, geographic location, nutritional status, biochemical risk factors, underlying heart disease, and genetic-environmental interaction, among other factors. Pediatric onset HFpEF is often not the same disease as in adults. Advances in the noninvasive evaluation of the LV diastolic function by strain, and strain rate analysis with speckle-tracking echocardiography, tissue Doppler imaging, and cardiac magnetic resonance imaging have increased our understanding of the HFpEF in children. This review addresses HFpEF in children and identifies knowledge gaps in the underlying etiologies, pathogenesis, diagnosis, and management, especially compared to adults with HFpEF.

We evaluated the impact of pediatric heart-allocation policy changes over time and the approval of the Berlin ventricular assist device (VAD) on waitlist (WL) outcomes for children with congenital heart disease (CHD).The Scientific Registry of Transplant Recipients database was evaluated to include all children (age18) with CHD and cardiomyopathy (CMP) on the WL between 1999 and 2019, divided into 4 eras: Era 1 (1999-2008); Era 2 (2009-2011); Era 3 (2012-2016); and Era 4 (2016-2019). WL characteristics and survival outcomes were evaluated for patients with CHD over time and were compared to those with CMP listed currently (Era 4).We included 5185 children with CHD on the WL during the study period; 1999 (39%) were listed in Era 1; 693 (13%) in Era 2; 1196 (23%) in Era 3; and 1297 (25%) in Era 4. Compared to the CHD WL in eras 1 and 2, those in Era 4 were less likely to be infants (48% vs 49% vs 43%), on mechanical ventilation (30% vs 26% vs 19%), on extracorporeal membrane oxygenation (15% vs 9.7% vs 6.2%), and were more likely to be on a VAD (2.4% vs 2.2% vs 6.0%) (P.05 for all). WL survival improved in children with CHD from Era 1 to Era 4 (P.001). However, in Era 4, children with CHD had lower WL survival than those with CMP (P.001).Children with CHD are increasingly being listed with less advanced heart failure, and they have had improved WL survival over time; however, WL outcomes remain inferior to those with CMP. Advances in pediatric medical and VAD therapy may improve future WL outcomes.

Introduction: Cardiovascular disease is the leading cause of death in children and young adults with chronic kidney disease (CKD) and kidney transplant. Phenotype of cardiac involvement may be variable. In adults with CKD, diastolic dysfunction has been shown to be an independent risk factor for mortality. However, there is overall very limited data in pediatric age group. Additionally, there are no guidelines for appropriate screening, assessment or standardized follow-up for cardiac pathology in pediatric CKD. The purpose of this study is to assess the overall cardiovascular burden and more specifically, diastolic dysfunction (DD) in pediatric CKD patients. Methods: Single center, retrospective cohort study of patients seen for CKD. Results: 237 patients with CKD /ESRD were identified including 64 patients who underwent renal transplant and 84 on chronic dialysis. Mean age was 14 years (7.6 to 17.5). Systolic hypertension was present in 49.7% while diastolic hypertension in 36.1%. 22% had a BMI greater than 95% percentile. Echocardiographic assessment showed preserved systolic function in majority (mean ejection fraction of 67.8%, range 19-90%). However, LV mass index(LVMI) was > 38 g/m2.7 in 66% (115/173). Tissue Doppler velocities demonstrated a large variation with significant abnormalities indicating abnormal myocardial performance and diastolic dysfunction. Mitral e velocity which was diminished in 79% while severely diminished in 31%. Mitral a,s and E/e’ velocities were abnormal in varying portion of population. Relative wall thickness was significantly increased (>0.41) in 112/213 patients. Serial measures showed a gradual increase in E/e’ ratio mean from 8.1 to 9.9 and increase in LVMI from mean of 44.5 to 53.1 g/m2.7 (p Conclusion: This is the largest study to date of demonstrating a significant cardiovascular burden in patients with CKD in the form of hypertrophy as well as abnormalities of myocardial performance and diastolic function. Serial measures show the parameters correlate with disease state. Further analysis in underway to identify risk factors and propose guidelines for serial screening.