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Background: Diastolic heart failure may be noted in paediatric patients with CHD, cardiomyopathy, or malignancies requiring chemotherapy, but the available data are scarce, and often derived from adult trials or based on theoretic or anecdotal evidence., Methods: Data between 2016 and 2021 were obtained from Pediatric Health Information System database. Patients <18 years of age with isolated diastolic heart failure admitted to ICU at some point during admission were included. They were divided into patients with and without inpatient mortality. Patients' demographics, comorbidities using ICD-10 codes, and pharmacologic interventions were also recorded. Univariate analysis was done in demographics, comorbidities, pharmacologic interventions, and mechanical interventions between admissions with and without mortality. Multivariable logistic regression was done for inpatient mortality and multivariable linear regression was done for total hospital length of stay in survivors., Results: Isolated diastolic heart failure comprised 0.5% of critically ill paediatric patients. A total of 121 (5%) experienced mortality among the 2,273 admissions in the final analyses. Milrinone and angiotensin converting enzyme inhibitor were found to be associated with decreased mortality. Increasing age and diuretics were associated with decreased total hospital length of stay in survivors., Conclusion: In the cohort studied, isolated diastolic left heart failure has a 5% mortality. Several comorbidities and interventions are associated with increased mortality with milrinone and angiotensin converting enzyme inhibitors being associated with decreased risk of mortality. When only admissions with survival to discharge are considered, older age and diuretics are associated with lower total hospital length of stay.

Introduction: Cardiac intensive care providers require a comprehensive understanding of cardiac output and oxygen delivery. The estimation of cardiac output in clinical practice often relies on thermodilution and the Fick principle. Central venous saturation and lactate levels are commonly used indicators for cardiac output assessment. However, the relationship between venous lactate levels and venous oxygen saturation in paediatric cardiac intensive care patients remains unclear., Methods: This is a single-centre retrospective pilot study aimed to investigate the correlation between venous lactate and venous oxygen saturation in paediatric patients. Data collected included venous saturation, heart rate, mean arterial blood pressure, arterial saturation by pulse oximetry, cerebral and renal near-infra-red spectroscopy values, and the presence of a functionally univentricular heart. Statistical analyses included Bayesian Pearson correlation and regression analyses., Results: A total of 203 data points from 37 unique patients were included in the analysis. There was no significant correlation between serum lactate and venous saturation (correlation coefficient = -0.01; Bayes factor 10 = 0.06). Serum lactate also did not correlate with other haemodynamic metrics. Venous saturation showed correlations with arterial saturation and cerebral and renal near-infra-red spectroscopy. Regression analysis revealed that parallel circulation, arterial saturation, and cerebral near-infra-red spectroscopy were predictive of venous saturation. The following equation resulted from the regression analysis: 68.0 - (12.7 x parallel circulation) - (0.8 x arterial saturation) + (0.3 x cerebral near-infra-red spectroscopy). This model had a Bayes factor 10 of 0.03 and adjusted R -squared was 0.29., Conclusion: In paediatric cardiac intensive care patients, there is no significant correlation between venous lactate and venous saturation, suggesting that lactate may not be a reliable marker for assessing the adequacy of oxygen delivery in this population. Only a weak correlation could be identified once the venous saturation was 70% or lower. Additional research is needed to explore alternative markers for monitoring oxygen delivery in critically ill paediatric patients.

Despite recent advances, hypoplastic left heart syndrome (HLHS) patients subsequent to the Fontan still have significant morbidity and mortality. Some require heart transplant due to systemic ventricular dysfunction. Limited data exist on timing for transplant referral. This study aims to correlate systemic ventricular strain by echocardiography to transplant-free survival. HLHS patients who had Fontan palliation at our institution were included. Patients were divided into: 1) Required transplant or experienced mortality (composite end point); 2) Did not require transplant or survived. For those who experienced the composite endpoint, the last echocardiogram prior to the composite outcome was used, while for those who did not experience the composite endpoint the last echocardiogram obtained was used. Several qualitative and quantitative parameters were analyzed with focus on strain parameters. Ninety-five patients with HLHS Fontan palliation were identified. Sixty-six had adequate images and eight (12%) experienced transplant or mortality. These patients had greater myocardial performance index by flow Doppler (0.72 versus 0.53, p = 0.01), higher systolic/diastolic duration ratio (1.51 versus 1.13, p = 0.02), lower fractional area change (17.65 versus 33.99, p < 0.01), lower global longitudinal strain (GLS) (-8.63 versus - 17.99, p < 0.01), lower global longitudinal strain rate (GLSR) (- 0.51 versus - 0.93, p < 0.01), lower global circumferential strain (GCS) (-6.68 versus -18.25, p < 0.01), and lower (GCSR) global circumferential strain rate (-0.45 versus -1.01, p < 0.01). ROC analysis demonstrated predictive value for GLS - 7.6 (71% sensitive, 97% specific, AUC 81%), GLSR -0.58 (71% sensitive, 88% specific, AUC 82%), GCS - 10.0 (86% sensitive, 91% specific, AUC 82%), and GCSR -0.85 (100% sensitive, 71% specific, AUC 90%). GLS and GCS can help predict transplant-free survival in patients with hypoplastic left heart syndrome having undergone Fontan palliation. Higher strain values (closer to zero) may be a helpful tool in determining when transplant evaluation is warranted in these patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Current practice regarding timing of feed initiation and feed tolerance largely relies on anecdotal practice and protocols. This study aims to provide an objective measure to guide clinical practice by analyzing changes in splanchnic regional oxygen saturation and Doppler patterns with feeds., Methods: A systematic review was performed. Inclusion criteria were: 1) patients under 1 year of age; 2) splanchnic regional oxygen saturation with near infrared spectroscopy before and after feeds or mesenteric Doppler findings before and after feeds; and 3) clinical parameters must have been presented as either mean and standard deviation or median and range. Endpoints of interest included splanchnic regional oxygen saturation, splanchnic systolic velocity, and splanchnic diastolic velocity. Meta-analyses were conducted using an inverse-variance model. The pooled effects are reported as mean difference and 95% confidence interval. Meta-regression was conducted for each endpoint with the following independent variables entered into the model: study year, gestational age, birth weight, time to measurement, and age at time of study., Results: This study included 8 studies with a total of 240 patients. Splanchnic regional oxygen saturation did not significantly differ after feeds (mean difference +1.0, 95% CI -2.9 to 4.9, p-value 0.62). Sensitivity analyses demonstrated that gestational age under 28 weeks was associated with a significant decrease in splanchnic regional oxygen saturation and GA over 30 weeks was not. Splanchnic artery systolic velocity was significantly higher after feeds (mean difference +34.0 cm/s, 95% CI 11.1-57.0 cm/s, p-value <0.01). Sensitivity analyses for gestational age and birth weight did not find any significant difference in pooled effect., Conclusion: Splanchnic regional oxygen saturation was significantly decreased after feeds in those patients under 28 weeks of gestation compared to those over 30 weeks. Systolic and diastolic Doppler velocities were significantly higher after feeds without differences in gestational age., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Background: In pediatric critical care, vasoactive/inotropic support is widely used in patients with heart failure, but it remains controversial because the influence of multiple medications and the interplay between their inotropic and vasoactive effects on a given patient are hard to predict. Robust evidence supporting their use and quantifying their effects in this group of patients is scarce., Study Question: The aim of this study was to characterize the effect of vasoactive medications on various cardiovascular parameters in pediatric patient with decreased ejection fraction., Study Design: Clinical-data based physiologic simulator study., Measure and Outcomes: We used a physics-based computer simulator for quantifying the response of cardiovascular parameters to the administration of various types of vasoactive/inotropic medications in pediatric patients with decreased ejection fraction. The simulator allowed us to study the impact of increasing medication dosage and the simultaneous administration of some vasoactive agents. Correlation and linear regression analyses yielded the quantified effects on the vasoactive/inotropic support., Results: Cardiac output and systemic venous saturation significantly increased with the administration of dobutamine and milrinone in isolation, and combination of milrinone with dobutamine, dopamine, or epinephrine. Both parameters decreased with the administration of epinephrine and norepinephrine in isolation. No significant change in these hemodynamic parameters was observed with the administration of dopamine in isolation., Conclusions: Milrinone and dobutamine were the only vasoactive medications that, when used in isolation, improved systemic oxygen delivery. Milrinone in combination with dobutamine, dopamine, or epinephrine also increased systemic oxygen delivery. The induced increment on afterload can negatively affect systemic oxygen delivery., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The primary objective of this study was to determine whether or not hemodynamic parameters and laboratory values at the time of admission to the pediatric cardiac intensive care unit after the Norwood operation were associated with a composite outcome of either need for extracorporeal membrane oxygenation or inpatient mortality. This was a single-center retrospective study of infants with functionally univentricular hearts admitted to intensive care after the Norwood procedure from January 2011 to January 2020. Data were obtained at a single point (after a Norwood procedure) and then compared between two subsets of patients based on the presence or not of the composite outcome of interest. In univariate and multiple regression analyses, a series of receiver operator curves were generated to assess the relationship between the variables of interest and the composite outcome. Eight (7.6%) experienced the composite outcome out of a total of 104 patients. Those who experienced the composite endpoint had significantly higher oxygen extraction ratio (0.43 vs. 0.31, p = 0.01), lower systemic blood flow (2.5 L/min versus 3.1 L/min, p = 0.01), and higher systemic vascular resistance (20.2 indexed woods units versus 14.8 indexed woods units, p = 0.01). Those with systemic blood flow of less than 2.5 L/min/m 2 had a 17% risk of experiencing the composite endpoint AUC = 0.79. Those with systemic vascular resistance of greater than 19 indexed woods units had a 22% risk of experiencing the composite endpoint AUC 0.80. Systemic blood flow and systemic vascular resistance are independently associated with this composite outcome., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Monitoring venous saturation allows identification of inadequate systemic oxygen delivery. The aim was to develop a model using non-invasive haemodynamic variables to estimate the inferior caval vein saturation and to determine its prognostic utility., Methods: This is a single-centre, retrospective study. A Bayesian Pearson's correlation was conducted to model the inferior caval vein saturation. Next, a Bayesian linear regression was conducted for data from all the patients and from only those with parallel circulation. Venous saturation estimations were developed. The correlation of these estimates to the actual inferior caval vein saturation was assessed. The resulting models were then applied to two validation cohorts: biventricular circulation (arterial switch operation) and parallel circulation (Norwood operation)., Results: One hundred and thirteen datasets were collected across 15 patients. Of which, 65% had parallel circulation. In all patients, the measured and estimated inferior caval vein saturations had a moderate and significant correlation with a coefficient of 0.64. In patients with parallel circulation, the measured and estimated inferior caval vein saturation had a moderate and significant correlation with a coefficient of 0.61. In the biventricular circulation cohort, the estimated inferior caval vein saturation had an area under the curve of 0.71 with an optimal cut-off of 49. In the parallel circulation cohort, the estimated interior caval vein saturation had an area under the curve of 0.83 with an optimal cut-off of 24%., Conclusion: The inferior caval vein saturation can be estimated utilising non-invasive haemodynamic data. This estimate has correlation with measured inferior caval vein saturations and offers prognostic utility.

Background: Maintaining the adequacy of systemic oxygen delivery is of utmost importance, particularly in critically ill children. Renal oxygen extraction can be utilised as metric of the balance between systemic oxygen delivery and oxygen consumption. The primary aim of this study was to determine what clinical factors are associated with renal oxygen extraction in children after Norwood procedure., Methods: Mechanically ventilated children who underwent Norwood procedure from 1 September, 2022 to 1 March, 2023 were identified as these patients had data collected and stored with high fidelity by the T3 software. Data regarding haemodynamic values, fluid balance, and airway pressure were collected and analysed using Bayesian regression to determine the association of the individual metrics with renal oxygen extraction., Results: A total of 27,270 datapoints were included in the final analyses. The resulting top two models explained had nearly 80% probability of being true and explained over 90% of the variance in renal oxygen extraction. The coefficients for each variable retained in the best were -1.70 for milrinone, -19.05 for epinephrine, 0.129 for mean airway pressure, -0.063 for mean arterial pressure, 0.111 for central venous pressure, 0.093 for arterial saturation, 0.006 for heart rate, -0.025 for respiratory rate, 0.366 for systemic vascular resistance, and -0.032 for systemic blood flow., Conclusion: Increased milrinone, epinephrine, mean arterial pressure, and systemic blood flow were associated with decreased (improved) renal oxygen extraction, while increased mean airway pressure, central venous pressure, arterial saturation, and systemic vascular resistance were associated with increased (worsened) renal oxygen extraction.

Introduction: In critical care, monitoring adequate tissue oxygenation is essential. Mixed venous oxygen saturation has traditionally been considered the gold standard for measuring cardiac output, which represents systemic oxygen delivery. Studies have shown that hepatic vein saturation is correlated with mixed venous oxygen saturation and mortality. The primary aim of this study was to determine the correlation between hepatic vein saturation and mixed venous saturation, and the impact of clinical characteristics on this correlation., Evidence Acquisition: A systematic review of the literature was performed to identify manuscripts. They must have included patients who received simultaneous mixed venous saturations and hepatic vein saturations, and the data for both must have been explicitly shared. Data were pooled from these studies to analyze the correlation between mixed venous saturation and the corresponding hepatic vein saturation., Evidence Synthesis: A total of 13 studies with 333 patients were included in the final analyses. The average age across these studies was 60.3±5.2. The pooled correlation between the mixed venous saturation and hepatic vein saturation was 0.88, demonstrating a strong correlation between the two. The average mixed venous saturation was 73.3±5.0 while the average hepatic vein saturation was 59.5±11.1., Conclusions: In these pooled analyses, hepatic vein saturation has a strong correlation with mixed venous saturation. This correlation is not significantly impacted by patient age, weight, or clinical setting. Nonetheless, further prospective studies are needed for confirmation.

Postoperative atrioventricular block may occur after pediatric cardiac surgery. A small proportion of those who develop atrioventricular block will require pacemaker placement. The primary aim of this study was to determine factors associated with postoperative atrioventricular block. Secondary aims included determining factors associated with pacemaker placement in those with atrioventricular block. Data from the PHIS data were utilized to identify patients under 18 years of age who underwent cardiac surgery. Those who did and did not develop atrioventricular block. Univariable analyses and regression analyses were conducted to determine factors associated with postoperative atrioventricular block. Similar analyses were conducted to determine factors associated with pacemaker placement in those with atrioventricular block. A total of 43,716 admissions were identified. Of these, 2093 (5%) developed atrioventricular block and 480 (1% of total admissions) underwent pacemaker placement. Approximately 70% of those with atrioventricular block received steroids but this was not associated with a decrease in pacemaker placement. Risk factors (congenital malformations of the heart, comorbidities, medications) associated with increased risk of atrioventricular block and pacemaker placement were identified. Postoperative atrioventricular block occurred in 5% of pediatric admissions for cardiac surgery. Of these admissions with postoperative atrioventricular block, 23% required pacemaker placement. Isoproterenol and steroids were not associated with a reduction in the likelihood of pacemaker placement., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Critical illness-related corticosteroid insufficiency (CIRCI) can cause hemodynamic instability in neonates after congenital heart surgery with manifestations that increase morbidity and potential mortality. We retrospectively reviewed neonates who underwent cardiac surgery between August 2018 and July 2020 at a freestanding children's hospital, had next-generation sequencing performed, and had their cortisol levels drawn as standard clinical care after cardiac surgery. The groups were defined as CIRCI (with a cortisol level ≤ 4.5 mcg/dL) and non-CIRCI (level > 4.5 mcg/dL). The CIRCI group (n = 8) had a 100% incidence of heterozygous gene mutation on STX1A with splicing or loss of function, and this mutation was not found in the non-CIRCI group (n = 8). Additional gene mutations were found in the CIRCI group on RAB6A, ABCA3, SIDT2, and LILRB3, with no incidence in the non-CIRCI group. Three additional mutations were found across the CIRCI group in INPPL1 and FAM189A2 (both splicing and missense), with 12-25% of patients in the non-CIRCI group also displaying these mutations. Novel genetic abnormalities were seen in neonates with symptoms of CIRCI with potential cardiac implications from a gene mutation for STX1A. Compounding effects of additional gene mutations need to be confirmed and explored for potential predisposition to hemodynamic instability during times of stress.

Purpose: The purpose of this study was to determine factors significantly associated with mortality and length of stay (LOS) in admissions to the pediatric intensive care unit (PICU) for traumatic brain injury (TBI)., Methods: A cross-sectional, retrospective cohort study that identified PICU admissions with TBI from forty-nine hospitals in the USA using the Pediatric Health Information System database from 2016 to 2021. Univariable analyses comparing those who did and did not experience mortality were performed. The following regression analyses were conducted: logistic regression with mortality as dependent variable; linear regression with LOS as the dependent variable; logistic regression with mortality as the dependent variable but only included patients with cerebral edema; and linear regression with LOS as the dependent variable but only included patients who survived. From the regression analysis for mortality in all TBI patients was utilized to develop a mortality risk score., Results: A total of 3041 admissions were included. Those with inpatient mortality (18.5%) tended to be significantly younger (54 vs. 92 months, p < 0.01), have < 9 pediatric Glasgow Coma Scale on admission (100% vs. 52.9%, p < 0.01) and more likely to experience acute renal, hepatic and respiratory failure, acidosis, central diabetes insipidus, hyperkalemia, and hypocalcemia. Regression analysis identified that pediatric Glasgow Coma Scale, alkalosis and cardiac arrest significantly increased risks of mortality. The TBI mortality risk score had an area under the curve of 0.89 to identify those with mortality; a score of 6 ≤ was associated with 88% mortality., Conclusion: Patients admitted to the PICU with TBI have 18.5% risk of inpatient mortality with most occurring the first 48 h and these are characterized with greater multisystem organ dysfunction, received medical and mechanical support. TBI mortality risk score suggested is a practical tool to identify patients with an increase likelihood to die., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: There are a variety of approaches to biventricular repair in neonates and infants with adequately sized ventricles and left-sided obstruction in the presence of a ventricular septal defect. Those who undergo this in a staged manner initially undergo a Norwood procedure followed by a ventricular septal defect closure such that the neo-aorta is entirely committed to the left ventricle and placement of a right ventricular to pulmonary artery conduit (Yasui operation). This study aimed to determine clinical and haemodynamic factors upon paediatric cardiac ICU admission immediately after the two-stage Yasui operation that was associated with post-operative length of stay., Methods: This was a retrospective review of patients who underwent the Yasui procedure after the initial Norwood operation between 1 January 2011 and 31 December 2020. Patients with complete data on admission were identified and analysed using Bayesian regression analysis., Results: A total of 15 patients were included. The median age was 9.0 months and post-operative length of stay was 6days. Bayesian regression analysis demonstrated that age, weight, heart rate, mean arterial blood pressure, central venous pressure, pulse oximetry, cerebral near infrared spectroscopy, renal near infrared spectroscopy, pH, pCO2, ionised calcium, and serum lactate were all associated with post-operative length of stay., Conclusion: Discrete clinical and haemodynamic factors upon paediatric cardiac ICU admission after staged Yasui completion are associated with post-operative length of stay. Clinical target ranges can be developed and seem consistent with the notion that greater systemic oxygen delivery is associated with lower post-operative length of stay.

Continuous monitoring software, T3, has an integrated index called the inadequate oxygen delivery index 50% (IDO2-50) which displays a probability that the mixed venous saturation is below a user-selected threshold of 30-50%. The primary aim of this study was to determine the correlation of the IDO2-50 with a measured venous saturation. The secondary aim of this study was to characterize the hemodynamic factors that contributed to the IDO2-50. This single-center, retrospective study aimed to characterize the correlation between IDO2-50 and inferior vena cava (IVC) saturation. A Bayesian Pearson correlation was conducted to assess the correlation between the collected variables of interest, with a particular interest in the correlation between the IDO2-50 and the IVC saturation. Receiver operator curve (ROC) analysis to assess the ability of the IDO2-50 to identify when the venous saturation was less than 50%. Bayesian linear regression was done with the IDO2-50 (dependent variable) and other independent variables. A total of 113 datasets were collected across 15 unique patients. IDO2-50 had moderate correlation with the IVC saturation (correlation coefficient - 0.569). The IDO2-50 had a weak but significant correlation with cerebral near-infrared spectroscopy (NIRS) values, a weak but significant correlation with heart rate, and a moderate and significant correlation with arterial saturation. ROC analysis demonstrated that the IDO2-50 had a good ability to identify a venous saturation below 50%, with an area under the curve of 0.797, cutoff point of 24.5 with a sensitivity of 81%, specificity of 66%, positive predictive value of 44%, and negative predictive value of 91%. Bayesian linear regression analysis yielded the following model: 237.82 + (1.18 × age in months) - (3.31 × arterial saturation) - (1.92 × cerebral NIRS) + (0.84 × heart rate). The IDO2 index has moderate correlation with IVC saturation. It has good sensitive and negative predictive value. Cerebral NIRS does appear to correlate better with the underlying venous saturation than the IDO2 index., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Kawasaki disease is a vasculitis that can lead to cardiac complications, including coronary artery disease and cardiogenic shock. Various scoring systems have been developed to determine those that will be refractory to routine intravenous immunoglobulin therapy or develop coronary artery disease. The objective of this study was to determine if the neutrophil-lymphocyte ratio could predict refractory disease and coronary artery lesions in patients with Kawasaki disease., Methods: A systematic review of the literature was performed to identify manuscripts describing comparisons of neutrophil-lymphocyte ratio between those who had refractory disease and those who did not, and between those who developed coronary artery lesions and those who did not. Mean difference was compared between groups. Areas under the curve were utilised to determine the pooled area under the curve., Results: 12 studies with 5593 patients were included in the final analyses of neutrophil-lymphocyte ratio for the prediction of refractory disease. Neutrophil-lymphocyte ratio before therapy was higher in refractory disease with a mean difference of 2.55 (p < 0.01) and pooled area under the curve of 0.724. Neutrophil-lymphocyte ratio after therapy was higher in refractory disease with a mean difference of 1.42 (p < 0.01) and pooled area under the curve for of 0.803. Five studies with 1690 patients were included in the final analyses of neutrophil-lymphocyte ratio for the prediction of coronary artery lesions. Neutrophil-lymphocyte ratio before therapy was higher in coronary artery lesions with a mean difference of 0.65 (p < 0.01)., Conclusion: The use of neutrophil-lymphocyte ratio may help physicians in the identification of patients at risk of refractory disease and coronary artery lesions in patients with Kawasaki disease.

Chronic myeloid leukemia (CML) is a well-characterized oncological disease in which virtually all patients possess a translocation (9;22) that generates the tyrosine kinase BCR::ABL1 protein. This translocation represents one of the milestones in molecular oncology in terms of both diagnostic and prognostic evaluations. The molecular detection of the BCR::ABL1 transcription is a required factor for CML diagnosis, and its molecular quantification is essential for assessing treatment options and clinical approaches. In the CML molecular context, point mutations on the ABL1 gene are also a challenge for clinical guidelines because several mutations are responsible for tyrosine kinase inhibitor resistance, indicating that a change may be necessary in the treatment protocol. So far, the European LeukemiaNet and the National Comprehensive Cancer Network (NCCN) have presented international guidelines on CML molecular approaches, especially those related to BCR::ABL1 expression. In this study, we show almost three years' worth of data regarding the clinical treatment of CML patients at the Erasto Gaertner Hospital, Curitiba, Brazil. These data primarily comprise 155 patients and 532 clinical samples. BCR::ABL1 quantification by a duplex-one-step RT-qPCR and ABL1 mutations detection were conducted. Furthermore, digital PCR for both BCR::ABL1 expression and ABL1 mutations were conducted in a sub-cohort. This manuscript describes and discusses the clinical importance and relevance of molecular biology testing in Brazilian CML patients, demonstrating its cost-effectiveness.

Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare disease with an acute and severe clinical presentation. The anti-von Willebrand factor caplacizumab was licensed for adults with aTTP based on prospective controlled trials. However, until now, there was no Brazilian experience with this new treatment modality. This retrospective, multicenter, single-arm, expanded access program (EAP) with caplacizumab, plasma exchange (PEX), and immunosuppression was conducted between 02/24/21 and 04/14/21, and enrolled 5 Brazilian patients with aTTP. EAP allowed access to caplacizumab in Brazil and real-world data was collected, at a time when the medication was not commercially available in Brazil. The median age was 31 years old, most patients were women (80%), and neurological manifestation was observed in 80% of cases. The median of laboratory tests was hemoglobin (Hb) of 11 g/dL, platelets (16.1 × 10 9 /L), lactic dehydrogenase (LDH) of 1471 U/L, creatinine (0.7 mg/dL), ADAMTS13 activity lower than 0.71%, and PLASMIC score of 6. All patients received immunosuppression, PEX, and caplacizumab. Until clinical response was achieved, the median was 3 sessions of PEX and 3 days of treatment. The median time of caplacizumab use was 35 days, with platelet normalization in 2 days after starting the drug. The median total length of stay was 8 days. All patients achieved clinical response and clinical remission, with a good safety profile. There was rapid clinical response, few PEX sessions were necessary, and there were short hospital stay, absence of refractoriness, little exacerbation, no death, and resolution of signs and symptoms at diagnosis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sample size and statistical power are often limited in pediatric cardiology studies due to the relative infrequency of specific congenital malformations of the heart and specific circulatory physiologies. The primary aim of this study was to determine what proportion of pediatric cardiology randomized controlled trials achieve an 80% statistical power. Secondary aims included characterizing reporting habits in these studies. A systematic review was performed to identify pertinent pediatric cardiology randomized controlled trials. The following data were collected: publication year, journal, if "power" or "sample size" were mentioned if a discrete, primary endpoint was identified. Power analyses were conducted to assess if the sample size was adequate to demonstrate results at 80% power with a p-value of less than 0.05. A total of 83 pediatric cardiology randomized controlled trials were included. Of these studies, 48% mentioned "power" or "sample size" in the methods, 49% mentioned either in the results, 12% mentioned either in the discussion, and 66% mentioned either at any point in the manuscript. 63% defined a discrete, primary endpoint. 38 studies (45%) had an adequate sample size to demonstrate differences with 80% power at a p-value of less than 0.05. A majority of these are not powered to reach the conventionally accepted 80% power target. Adequately powered studies were found to be more likely to report "power" or "sample size" and have a discrete, primary endpoint., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Surfactant has been routinely used in the neonatal population, particularly in the setting of prematurity and neonatal respiratory distress syndrome. Current evidence, however, does not delineate the effect of surfactant use in neonates and older children during cardiac surgery admissions. This study aimed to characterize the impact of surfactant on pediatric cardiac surgery admissions., Methods: Admissions of those under 18 years of age with cardiac surgery were identified from the Pediatric Health Information System (PHIS) database between 2004 and 2015, using ICD-9 procedure codes. Univariate analyses were conducted to compare admission characteristics between those that did and not utilize surfactant. Variables shown to be significant were then entered as independent variables into the regression analyses. Surfactant was entered into each model as an independent variable., Results: A total of 81,313 admissions met the inclusion criteria. Of these, 109 (0.1%) had surfactant utilized. Univariate analyses identified several differences between admissions with and without surfactant use and demonstrated significantly increased mortality in the surfactant group (38.5% versus 4.6%, p  < .01). Regression analyses demonstrated that surfactant was independently associated with increased mortality (odds ratio 6.0, 95% confidence interval 3.9-9.3, p  < .01). Univariate analysis in only surfactant admissions demonstrated the following to be associated with inpatient mortality: younger age, prematurity, Ebstein anomaly, and hypoplastic left heart syndrome., Conclusions: Surfactant administration during pediatric cardiac surgery admissions is independently associated with a sixfold increase in inpatient mortality. It is likely that these findings are mediated by augmentation of the decrease in pulmonary vascular resistance and a subsequent decrease in systemic blood flow in the setting of parallel circulation. Surfactant should be administered with special consideration in neonates with cardiac disease and may be best avoided in those with parallel circulation.

Despite the controversy, sodium bicarbonate is a commonly used medication in critically ill patients of all ages. There is a lack of data on the acute impact on hemodynamic parameters, biomarker indicators of cardiac output, and changes in vasoinotropic support after sodium bicarbonate therapy. In our retrospective study on children with biventricular circulation in pediatric cardiac intensive care unit receiving bicarbonate therapy: we analyzed its effects on arterial blood gases, heart rate, blood pressure (BP), central venous pressures (CVP), cerebral and renal near-infrared spectroscopy (NIRS), changes in vasoinotropic and ventilator changes before and after sodium bicarbonate administration. Thirty-one administrations of sodium bicarbonate in 23 patients with congenital heart disease without residual shunts were analyzed. The average age was 15.4 months, weight 7.7 kg, and the average bicarbonate dose was 1 meq/kg. There was an increase in arterial pH from 7.24 to 7.30 (p = 0.14) and bicarbonate changed from 18 to 20 mEq/L (p = 0.23). No clinically significant changes were found in the following parameters: heart rate (141 ± 20.1 to 136 ± 19), systolic BP (84 ± 17 to 86 ± 14 mmHg), diastolic BP (48 ± 12 to 49 ± 12 mmHg), cerebral NIRS (64 ± 12 to 65 ± 12), renal NIRS (80 ± 10 to 81 ± 7), CVP (9 ± 3 to 10 ± 4 mmHg), paCO 2 (45 ± 26 to 42 ± 7 mmHg), paO 2 (143 ± 78 to 127 ± 59 mmHg), serum lactate (2.2 ± 2.7 to 3.6 ± 3.8 mmol/L), and vasoinotropic score (7.5 ± 5.0 to 7.7 ± 4.7). Outside of a change in serum pH and bicarbonate levels no other significant changes were noted after sodium bicarbonate administration in children with congenital heart disease with fully septated, biventricular circulation. There was no improvement in systemic oxygen delivery., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Blood oximetry provides a fundamental approach to blood gases for inpatients. Arterial blood gases (ABG) have been considered the gold standard for blood oximetry assessment. Venous blood gas (VBG) evaluation is frequently available and provides a source of a more comfortable method for the assessment of blood oximetry in pediatric patients. Some data provided by the venous blood gas can be additive and offer insights apart from the arterial blood gas. The purpose of this review was to provide an assessment of the performance of VBG in pediatric patients. The study concludes that VBG are helpful tools in assessing oxygenation and ventilation in critically ill children and can be used as a marker of adequacy of systemic oxygen delivery. In the setting of systemic oxygen delivery decrease or oxygen extraction increase, the partial pressure of oxygen on the VBG will decrease. Thus, the partial pressure of oxygen and the corresponding venous saturation can be a marker of systemic oxygen delivery in a variety of illnesses. Simultaneous ABG and VBG comparison can actually lend great insight to not only the respiratory status of a patient but provide an assessment of the adequacy of cardiac output and systemic oxygen delivery.

Background: Fluid boluses are frequently utilized in children. Despite their frequency of use, there is little objective data regarding the utility of fluid boluses, who they benefit the most, and what the effects are., Aims: This study aimed to conduct pooled analyses to identify those who may be more likely to respond to fluid boluses as well as characterize clinical changes associated with fluid boluses., Methods: A systematic review of the literature and meta-analysis was conducted to identify pediatric studies investigating the response to fluid boluses and clinical changes associated with fluid boluses., Results: A total of 15 studies with 637 patients were included in the final analyses with a mean age of 650 days ± 821.01 (95% CI 586 to 714) and a mean weight of 10.5 kg ± 7.19 (95% CI 9.94 to 11.1). The mean bolus volume was 12.14 ml/kg ± 4.09 (95% CI 11.8 to 12.5) given over a mean of 19.55 min ± 10.16 (95% CI 18.8 to 20.3). The following baseline characteristics were associated with increased likelihood of response [represented in mean difference (95% CI)]: greater age [207.2 days (140.8 to 273.2)], lower cardiac index [-0.5 ml/min/m 2 (-0.9 to -0.3)], and lower stroke volume [-5.1 ml/m 2 (-7.9 to -2.3)]. The following clinical parameters significantly changed after a fluid bolus: decreased HR [-5.6 bpm (-9.8 to -1.3)], increased systolic blood pressure [7.7 mmHg (1.0 to 14.4)], increased mean arterial blood pressure [5.5 mmHg (3.1 to 7.8)], increased cardiac index [0.3 ml/min/m 2 (0.1 to 0.6)], increased stroke volume [4.3 ml/m 2 (3.5 to 5.2)], increased central venous pressure [2.2 mmHg (1.1 to 3.3)], and increased systemic vascular resistance [2.1 woods units/m 2 (0.1 to 4.2)]., Conclusion: Fluid blouses increase arterial blood pressure or cardiac output by 10% in approximately 56% of pediatric patients. Fluid blouses lead to significant decrease in HR and significant increases in cardiac output, stroke volume, and systemic vascular resistance. Limited published data are available on the effects of fluid blouses on systemic oxygen delivery., (© 2022 John Wiley & Sons Ltd.)

Introduction Propofol has long been used as an anesthetic agent during pediatric surgery. Its use in pediatric intensive care units has been largely controversial. A beneficial use of propofol is to facilitate weaning of other pain and sedation infusions such as opiates and benzodiazepines. However, some have advocated to not use propofol due to fear of possible adverse effects including propofol infusion syndrome and hemodynamic instability. The purpose of this study was to determine both the safety of propofol infusions in critically ill pediatric patients, as well as the change in the requirement of other pain and sedation infusions by use of a propofol infusion. Methods Single-center, retrospective data (January 2011 to January 2020) was obtained manually using a study-specific data extraction tool created for electronic medical records. The data obtained included variables of interest that measured physiological parameters and pain/sedation infusion (morphine, fentanyl, hydromorphone, midazolam, and dexmedetomidine) rates during three time periods: before propofol initiation, immediately after discontinuation, and four hours after discontinuation. The physiological parameters were then compared to the pain and sedation infusion rates using paired Wilcoxon signed-rank tests. Results There was a total of 33 patients with an average age of 11.1 years who were given a median initial propofol infusion of 50 mcg/kg/min with a peak dose of 75 mcg/kg/min over an average of eight hours. Age had a weak and insignificant correlation with initial rate and duration and a moderate and significant correlation with peak rate and duration. Physiological parameters did not vary at any time point measured. There was a significant reduction in other pain and sedation infusions after discontinuation of propofol. Conclusion Propofol infusions are hemodynamically tolerated and the majority of patients who are on other pain and sedation infusions tolerate complete discontinuation of these infusions following propofol discontinuation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Uppuluri et al.)

The complete blood count (CBC) is one of the most requested tests by physicians. CBC tests, most realized in conventional hematological analyzers, are restricted to centralized laboratories due to frequent maintenance, large devices, and expensive costs required. On the other hand, most handheld CBC devices commercially available show high prices and are not liable to calibration or control procedures, which results in poor quality compared to standard hematology instruments. The Hilab system is a small-handed hematological platform that uses microscopy and chromatography techniques for blood cells and hematimetric parameters analysis through artificial intelligence, machine learning, and deep learning techniques. For clinical evaluation of the handheld CBC device, 450 blood samples were analyzed. The samples encompassed normal (82%) and pathological conditions (18%), such as thalassemias (2.2%), anemias (6.6%), and infections (9.2%). For all analytes, accuracy, precision, method comparison, and flagging capabilities of the Hilab System, were compared with the Sysmex XE-2100 (Sysmex, Japan) results. The sample source (venous and capillary) influences were also evaluated. Pearson correlation, Student t test, bias, and the Bland-Altman plot of each blood count analyte were calculated and shown. The significance level was set at p ≤ 0.05. For clinical evaluation, Hilab System and the Sysmex XE-2100 showed a strong correlation (r ≥ 0.9) for most evaluated parameters. In the precision study, analytes showed CV inside the limits established according to European Federation of Clinical Chemistry and Laboratory Medicine guidelines. The flagging capabilities of the Hilab system, compared to the manual microscopy technique, presented high sensibility, specificity, and accuracy. Venous and capillary samples (p > 0.05) do not differ statistically. Considering the need for point-of-care CBCs, the study indicated that the Hilab system provides fast, accurate, low cost, and robust analysis for reliable clinical use., (© 2022. The Author(s).)

Introduction: The primary objective of this study was to determine whether Altmetric score, number of reads, and citations for paediatric cardiology manuscripts correlate with one another. A secondary objective was to determine the extent to which factors mediated citation number for paediatric cardiology manuscripts., Methods: Data for this study came from manuscripts published in Cardiology in the Young (2010-2021). Data were extracted by using data shared on the journal website. Spearman's correlation analyses were conducted between manuscript reads, citations, and Altmetric score. Regression analyses were conducted with number of citations as the dependent variable and year of publication, publication type, number of reads, and Altmetric score as independent variables., Results: A total of 2642 manuscripts were included in the final analyses. Reads and citations had poor correlation (r-value 0.32); reads and Altmetric score had negligible correlation (r-value 0.26); and Altmetric score and citations had negligible correlation (r-value 0.07). Year of publication was independently associated with number of citations (β -0.95, p-value <0.01). Manuscript type was independently associated with number of citations (β 1.04, p-value <0.01). Number of reads was independently associated with citations (β 0.01, p-value <0.01). Altmetric score was independently associated with number of citations (β 0.05, p-value <0.01)., Conclusion: This study describes the correlation of reads, citations, and Altmetric score in manuscripts published in Cardiology in the Young , demonstrating poor correlation, at best, between these metrics. Each bibliometric index seems to represent a different phenomenon of manuscript consumption. No single bibliometric index in isolation offers ample representation of manuscript consumption.

Introduction: In patients with right ventricular diastolic dysfunction after complete repair of tetralogy of Fallot, some employ the use of beta-blockade. The theoretical benefit of this therapy is felt to be one of the two: 1) reduction in heart rate with subsequent increase in diastolic filling time and stroke volume; 2) halting or reversal of right ventricular remodelling. This study aimed to characterise the use of beta-blockade in paediatric admissions with complete repair of tetralogy of Fallot and characterise the effects of beta-blockade on admission characteristics., Methods: Admissions from 2004 to 2015 in the Pediatric Health Information System database with complete repair of tetralogy of Fallot were identified. Characteristics between admissions with and without beta-blockade were compared by univariate analysis. Next, regression analyses were conducted to determine the independent association of beta-blockade on length of admission, billed charges, cardiac arrest, and inpatient mortality while controlling for demographic variables and comorbidities., Results: A total of 3594 admissions were included in the final analyses. Of these, 371 employed beta-blockade. Admissions with beta-blockade were more likely to have heart failure and tachyarrhythmias. These admissions also tended to be longer by univariate analysis. Regression analyses demonstrated that beta-blockade was independently associated with a 2.8-day increase in length of stay and no statistically significant change in billed charges, cardiac arrest, or inpatient mortality., Conclusions: Beta-blockade after complete repair of tetralogy of Fallot is associated with a longer length of stay but did not statistically significantly impact billed charges, cardiac arrest, or inpatient mortality.

What Is Known and Objective: Acute kidney injury (AKI) is a complication following surgery and has been associated with worsened patient outcomes. Providers have used agents that may confer a degree of renal protection in the perioperative stage. Such is the case of dexmedetomidine, a selective alpha-2 adrenergic agonist used in the intensive care unit (ICU) as a sedative agent. The primary objective of this meta-analysis was to characterize the use of dexmedetomidine and to evaluate its impact on renal markers and outcomes in patients after surgery., Methods: A systematic review of manuscripts was performed to identify patients who received dexmedetomidine after surgery by searching the PubMed, Embase, and Cochrane databases. The following parameters were captured: blood urea nitrogen (BUN), serum creatinine, creatinine clearance, neutrophil gelatinase-associated lipoprotein (NGAL), cystatin C, urine output, duration of mechanical ventilation, ICU length of stay, AKI, need for dialysis, and mortality., Results and Discussion: Nineteen studies with 3,395 patients were included in the analyses. The mean bolus and infusion dose of dexmedetomidine were 0.82 µg/kg and 0.54 mcg/kg/hr, respectively. There was a significant difference in creatinine clearance and NGAL in favour of the dexmedetomidine group. In addition, the dexmedetomidine group had a shorter ICU length of stay, and a lower risk of acute kidney injury and mortality compared to the control. There was no difference in the rest of the parameters., What Is New and Conclusion: Dexmedetomidine appears to have postoperative renal protective effects. This is evidenced by lower NGAL levels and increased creatinine clearance in those who received dexmedetomidine. These effects are associated with decreases in ICU length of stay and risk of AKI and mortality., (© 2021 John Wiley & Sons Ltd.)

The purpose of this study is to assess the effect of calcium bolus in response to a hypotensive episode by assessing high-fidelity hemodynamic data obtained from children with single-ventricle physiology with parallel circulation. Single-center, retrospective analysis of hemodynamic data after calcium bolus administrations within the first 2 weeks post-surgery. Time intervals were the baseline (- 60 to - 10 min); the hypotensive episode (- 10 to 0 min); time point zero at the bolus administration; and the response (0 to 60 min). The main responses assessed were the peak increase in mean blood pressure (mBP), duration of the response after the bolus, and markers of oximetric effects. These analyses included 128 boluses in 63 patients. Of the total boluses analyzed, 80% increased the mBP by 5 mmHg or higher with the effect lasting at least 10 min, whereas 10% of the boluses analyzed increased the mBP by 20 mmHg or higher with the effect lasting at least 50 min. The boluses induced a significant increase in arterial oxygen saturation and an upward trend in pulmonary-to-systemic flow ratio, without increasing renal or cerebral oxygen extraction ratios. Calcium chloride boluses are an effective rescue medication for hypotensive episodes in children with parallel circulation. They lead to an improvement in mBP, as well as an increase in pulmonary-to-systemic blood flow ratio. More importantly, these boluses do not compromise systemic oxygen delivery., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The primary objective of this study was to determine if serum lactate level at the time of hospital admission can predict mortality in pediatric patients. A systematic review was conducted to identify studies that assessed the utility of serum lactate at the time of admission to predict mortality in pediatric patients. The areas under the curve from the receiver operator curve analyses were utilized to determine the pooled area under the curve. Additionally, standardized mean difference was compared between those who survived to discharge and those who did not. A total of 12 studies with 2,099 patients were included. Out of these, 357 (17%) experienced mortality. The pooled area under the curve for all patients was 0.74 (0.67-0.80, p  < 0.01). The pooled analyses for all admissions were higher in those who experienced mortality (6.5 vs. 3.3 mmol/L) with a standardized mean difference of 2.60 (1.74-3.51, p  < 0.01). The pooled area under the curve for cardiac surgery patients was 0.63 (0.53-0.72, p  < 0.01). The levels for cardiac surgery patients were higher in those who experienced mortality (5.5 vs. 4.1 mmol/L) with a standardized mean difference of 1.80 (0.05-3.56, p  = 0.04). Serum lactate at the time of admission can be valuable in identifying pediatric patients at greater risk for inpatient mortality. This remained the case when only cardiac surgery patients were included., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

The purpose of these analyses was to determine how specific comorbidities and medical interventions impact risk of inpatient mortality in those with hypoplastic left heart syndrome undergoing Norwood procedure. The secondary aims were to determine the impact of these on billed charges, postoperative length of stay, and risk of cardiac arrest. Admissions from 2004 to 2015 in the Pediatric Health Information System database with hypoplastic left heart syndrome and Norwood procedure were identified. Admission characteristics, patient interventions, and the presence of comorbidities were captured. A total of 5,138 admissions were identified meeting inclusion criteria. Of these 829 (16.1%) experienced inpatient mortality, and 352 (6.7%) experienced cardiac arrest. The frequency of inpatient mortality did not significantly change over the course of the study era. The frequency of cardiac arrest significantly decreased from 7.4% in 2004 to 4.3% in 2015 (p = 0.04). The frequency of pharmacologic therapies, particularly vasoactive use, decreased as the study period progressed. Regression analyses demonstrated a significant association between cardiac arrest and inpatient mortality with arrhythmias, acute kidney injury, and pulmonary hypertension. Similarly, regression analyses demonstrated a significant association between increase in billed charges and length of stay with year of surgery, presence of heart failure, syndromes, and acute kidney injury. For patients with hypoplastic left heart syndrome undergoing the Norwood procedure, the frequency of pharmacologic therapies and cardiac arrest has decreased over time. There are significant associations between acute kidney injury, arrythmias, and pulmonary hypertension with cardiac arrest and mortality., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Packed red blood cell (PRBC) transfusions are commonly administered in pediatric patients following the Norwood operation. This study was conducted to determine the effect of PRBC transfusions on hemodynamic parameters in pediatric patients with single-ventricle physiology and parallel circulation. A single-center, retrospective chart review was conducted. Pediatric patients admitted to the cardiac intensive care unit after Norwood operation between 2017 and 2018 were identified. Hemodynamic parameters were collected within a four-hour period before and after a PRBC transfusion. Univariate analyses using paired t tests were conducted to compare blood gas values before and after PRBC transfusion. Next, multivariate regression analyses were conducted to model the impact of transfusion volume, change in hemoglobin levels, and change in FiO2 on the change in PaO2 and PaCO2. These analyses included data from 33 eligible patients who received a PRBC transfusion following a Norwood operation. The hemoglobin levels (p < 0.01) and the PaO2/FiO2 ratio (p = 0.04) were significantly increased, while arterial lactate levels (p = 0.03) were significantly decreased following the transfusion. Transfusion for a pre-transfusion hemoglobin of 12.4 g/dL appears to provide greatest reduction in lactate, used as a surrogate marker for systemic oxygen delivery. No significant changes were found in arterial pH, PaO2, and PaCO2. PRBC transfusions following the Norwood operation may be a useful intervention to increase systemic oxygen delivery, improving PaO2/FiO2 ratio and improving serum lactate. The benefits of PRBC transfusions must be weighed against previously identified risks on a patient-specific basis. Further studies are warranted to further delineate the effects of such transfusions in this population., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: There is limited information regarding the role of biomarker levels at predicting mortality in patients with the coronavirus disease (COVID-19) pandemic. The purpose of this study is to determine the differences in serum biomarker levels in adults with COVID-19 who survived hospitalization from those who did not., Methods: A comprehensive search was completed on PubMed, EMBASE and Cochrane libraries to identify studies of interest. Endpoints of interest were blood counts, hepatic function test, acute phase reactants, cytokines and cardiac biomarkers., Results: A total of 10 studies with 1584 patients were included in the pooled analyses. Biomarkers that were noted to be significantly higher in those who died from coronavirus disease included: white blood cell count, neutrophil count, C-reactive protein, high sensitivity C-reactive protein, procalcitonin, ferritin, D-dimer, interleukin-6, lactate dehydrogenase, creatine kinase, prothrombin time, aspartate aminotransferase, alanine aminotransferase, total bilirubin and creatinine. Lymphocyte count, platelet count and albumin were significantly lower in patients who died., Conclusion: This pooled analysis of 10 studies including 1584 patients identified significant differences in biomarkers on admission in patients who survived from those who did not. Further research is needed to develop risk stratification models to help with judicious use of limited health-care resources.

Invasive and non-invasive monitoring allow for early detection of hemodynamic compromise, facilitating timely intervention and avoidance of further decline. While venous oximetry is useful for assessing the adequacy of systemic oxygen delivery (DO 2 ), it is most often intermittent, invasive, and costly. Near-infrared spectroscopy (NIRS) oximetry allows for the non-invasive estimation of the adequacy of DO 2 . We assessed the correlation between cerebral NIRS oximetry and superior vena cava (SVC) and jugular venous (JV) oxygen saturations and between renal NIRS oximetry and inferior vena cava (IVC) oxygen saturations. Systematic review of the literature was conducted to identify studies with data regarding near-infrared spectroscopy and venous saturation. The PubMed, EMBASE, Medline, and Cochrane databases were queried using the following terms in isolation and various combinations: "congenital heart disease," "near infrared spectroscopy," "venous saturation," and "pediatric." Pediatric studies in which simultaneous NIRS oximetry and corresponding venous oxygen saturations were simultaneously collected after cardiac surgery or catheterization were identified. Data were pooled from these studies to analyze the correlation between NIRS oximetry and the corresponding venous oxygen saturations. A total of 16 studies with 613 patients were included in the final analyses. Data were present to compare cerebral and renal NIRS oximetry with corresponding venous oxygen saturation. Cerebral NIRS and SVC and JV oxygen saturations and renal NIRS and IVC oxygen saturations demonstrated strong degrees of correlation (r-value 0.70 for each). However, cerebral NIRS and IVC oxygen saturation had a week degree of correlation (r-value of 0.38). Pooled analyses demonstrate that cerebral NIRS oximetry correlates strongly with SVC or JV oxygen saturation while renal NIRS oximetry correlates strongly with IVC oxygen saturations. A weak correlation was noted between cerebral NIRS oximetry and IVC oxygen saturations., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To utilize publicly reported, state-level data to identify factors associated with the frequency of cases, tests, and mortality in the USA., Materials and Methods: Retrospective study using publicly reported data collected included the number of COVID-19 cases, tests and mortality from March 14th through April 30th. Publicly available state-level data was collected which included: demographics comorbidities, state characteristics and environmental factors. Univariate and multivariate regression analyses were performed to identify the significantly associated factors with percent mortality, case and testing frequency. All analyses were state-level analyses and not patient-level analyses., Results: A total of 1,090,500 COVID-19 cases were reported during the study period. The calculated case and testing frequency were 3332 and 19,193 per 1,000,000 patients. There were 63,642 deaths during this period which resulted in a mortality of 5.8%. Factors including to but not limited to population density (beta coefficient 7.5, p  < .01), transportation volume (beta coefficient 0.1, p  < .01), tourism index (beta coefficient -0.1, p  = .02) and older age (beta coefficient 0.2, p  = .01) are associated with case frequency and percent mortality., Conclusions: There were wide variations in testing and case frequencies of COVID-19 among different states in the US. States with higher population density had a higher case and testing rate. States with larger population of elderly and higher tourism had a higher mortality. Key messages There were wide variations in testing and case frequencies of COVID-19 among different states in the USA. States with higher population density had a higher case and testing rate. States with larger population of elderly and higher tourism had a higher mortality.

Hepatoportoenterostomy remains the cornerstone of treatment for biliary atresia. Current employed techniques include laparoscopy and open surgery. This study aims to determine if either method provides an advantage. Following PRISMA guidelines, a systematic review was conducted. Nineteen studies were included. Mean operative time 34.98 (95% CI 20.10, 49.85; p ≤ 0.00001) was longer in laparoscopic while bleeding volumes - 16.63 (95% CI - 23.39, - 9.86; p ≤ 0.00001) as well as the time to normal diet - 2.42 (95% CI - 4.51, - 0.32; p = 0.02) were lower in the laparoscopic group. No differences were observed in mean length of stay - 0.83. Similar complication, transfusions, postoperative cholangitis 0.97, and transplant free survival rates 1.00 (0.63, 1.60; p = 0.99) were seen between groups. Laparoscopic portoenterostomy provides advantages on operative time and bleeding as well as to normal diet when compared to open procedures. Both procedures showed no differences in length of stay, complications, cholangitis, and importantly, native liver survival. Level of evidence: III., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: To assess the efficacy of C-reactive protein (CRP) and procalcitonin (PCT) at identifying infection in children after congenital heart surgery (CHS) with cardiopulmonary bypass (CPB)., Materials and Methods: Systematic review of the literature was conducted to identify studies with data regarding CRP and/or PCT after CHS with CPB. The primary variables identified to be characterized were CRP and PCT at different timepoints. The main inclusion criteria were children who underwent CHS with CPB. Subset analyses for those with and without documented infection were conducted in similar fashion. A p value of less than .05 was considered statistically significant., Results: A total of 21 studies were included for CRP with 1655 patients and a total of 9 studies were included for PCT with 882 patients. CRP peaked on postoperative Day 2. A significant difference was noted in those with infection only on postoperative Day 4 with a level of 53.60 mg/L in those with documented infection versus 29.68 mg/L in those without. PCT peaked on postoperative Day 2. A significant difference was noted in those with infection on postoperative Days 1, 2, and 3 with a level of 12.9 ng/ml in those with documented infection versus 5.6 ng/ml in those without., Conclusions: Both CRP and PCT increase after CHS with CPB and peak on postoperative day 2. PCT has a greater statistically significant difference in those with documented infection when compared to CRP and a PCT of greater than 5.6 ng/ml should raise suspicion for infection., (© 2021 Wiley Periodicals LLC.)

The incidence of chylothorax is reported from 1-9% in pediatric patients undergoing congenital heart surgery. Effective evidenced-based practice is limited for the management of post-operative chylothorax in the pediatric cardiac intensive care unit. The study characterizes the population of pediatric patients with cardiac surgery and chylothorax who eventually require pleurodesis and/or thoracic duct ligation; it also establishes objective data on the impact of various medical interventions. Data were obtained from the Pediatric Health Information System database from 2004-2015. Inclusion criteria for admissions for this study were pediatric admissions, cardiac diagnosis, cardiac surgery, and chylothorax. These data were then divided into two groups: those that did and did not require surgical intervention for chylothorax. Other data points obtained included congenital heart malformation, age, gender, length of stay, billed charges, and inpatient mortality. A total of 3503 pediatric admissions with cardiac surgery and subsequent chylothorax were included. Of these, 236 (9.4%) required surgical intervention for the chylothorax. The following cardiac diagnoses, cardiac surgeries, and comorbidities were associated with increased odds of surgical intervention: d-transposition, arterial switch, mitral valvuloplasty, acute kidney injury, need for dialysis, cardiac arrest, and extracorporeal membrane oxygenation. Statistically significant medical interventions which did have an impact were specific steroids (hydrocortisone, dexamethasone, methylprednisolone) and specific diuretics (furosemide). These were significantly associated with decreased length of stay and costs. Dexamethasone, methylprednisolone, and furosemide were associated with decreased odds for surgical intervention. These analyses offer objective data regarding the effects of interventions for chylothorax in pediatric cardiac surgery admissions. Results from this study seem to indicate that most post-operative chylothoraxes should improve with furosemide, a low-fat diet, and steroids.

Objective: Clinical clerkships are a fundamental component of medical education where students' learning is aided by exposure to real patients in diverse practical settings. Countless programs use overnight call shifts as an essential part of their clerkships. There has been concerns about the negative effects these shifts have on students. The study aims to determine relations between call schedule, lecture attendance, and academic and clinical performance., Methods: One hundred and eight medical students were followed during their surgery clerkship. Students on a Q3 schedule had an on-call shift once every 3 nights, while students on a Q4 schedule once every 4 nights. Their academic performance was evaluated using their exams grades, while their clinical performance was evaluated by their attending physicians. Burnout syndrome was measured using Maslach Inventory., Results: A total of 108 medical students attended their surgical clerkship. Sixty-nine students were under the Q3 call schedule while 39 students in the Q4 call schedule. Mean lecture attendance for students in Q3 was 82.7% (17.3%) compared to 90% (11.2%) (p = 0.020). Final exam grades were different between groups, with Q3 scoring a mean 71.55 (9.3) compared to Q4 85.07 (9.8) (p = 0.001). Clinical performance score means were similar between groups (p = 0.777). Q4 had 74% and Q3 had 49.3% of the students with >90% of attendance (p = 0.008). Q4 had 2.6% students with <70% attendance compared to Q3 with 23.2% (p = 0.008). Students with >90% attendance regardless of call schedule, scored higher in both midterms and final exams (p = 0.002; p = 0.001). Burnout prevalence was higher in students on the Q3 schedule with 28.6% compared to 4.7% of those on the Q4 schedule (p = 0.003)., Conclusions: Students with less call frequency were associated with an improvement in lecture attendance and academic performance, and a lower burnout syndrome rate, without impacting clinical performance. Students with higher attendance regardless of call schedules performed higher academically. Further studies should evaluate the impact on clinical performance and exposure more thoroughly., (Copyright © 2020 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Vasopressin has been used to augment blood pressure; however, cardiovascular effects after cardiac surgery have not been well established. The primary objective of this study was to survey the current literature and quantify the pooled effect of vasopressin on hemodynamic parameters in children after pediatric cardiac surgery. A systematic review was conducted to identify studies characterizing the hemodynamic effects of vasopressin after pediatric cardiac surgery. Studies were assessed and those of satisfactory quality with pre- and post-vasopressin hemodynamics for each patient were included in the final analyses. 6 studies with 160 patients were included for endpoints during the first 2 h of infusions. Patients who received vasopressin infusion had greater mean, systolic, and diastolic blood pressures and lower heart rates at 2 h after initiation. 8 studies with 338 patients were included for the effects at 24 h. Patients who received vasopressin infusion had lower central venous pressures and decreased lactate concentrations 24 h after initiation. A subset analysis for children with functionally univentricular hearts found significant decrease in inotrope score and central venous pressure. A subset analysis for neonates found significant decrease in inotrope score and fluid balance. Vasopressin leads to decrease in heart rate and increase in blood pressure in the first 2 h of initiation. Later effects include decrease in inotrope score, central venous pressure, fluid balance, and in lactate within the first 24 h. Findings vary in neonates and in those with functionally univentricular hearts although beneficial effects are noted in both.

Acute renal injury (AKI) is a risk factor for the development of hypertension, which involves oxidative stress, changes in Na + handling, and the intrarenal renin-angiotensin-aldosterone system (RAAS) as underlying mechanisms. We investigated in rats whether renal ischemia-reperfusion (IR) leads to changes in the proximal tubule ATP-dependent Na + transport and the intrarenal content of RAAS components, as well as the role of NADPH oxidase. Rats weighing 300-350 g were submitted to AKI by bilateral IR (n = 25). After IR injury, the animals were followed up for 4 weeks. One part (n = 7) received daily treatment with the NADPH oxidase inhibitor apocynin (100 mg/kg, drinking water), while another part (n = 9) received apocynin 24 h before and after IR. One group was submitted to sham surgery (n = 8). Four weeks after IR, the rats presented elevated systolic blood pressure, as well as increased lipid peroxidation, NADPH oxidase activity, (Na + +K + )ATPase activity, and upregulation of type 1 angiotensin II receptor in the renal cortex. On the other hand, there was a decrease in Na + -ATPase activity and downregulation of the isoforms 1 and 2 of the angiotensin-converting enzyme, type 2 angiotensin II receptor, and of the α and ε isoforms of protein kinase C. Most of these alterations was prevented by both apocynin treatment protocols. Thus, we conclude that AKI-induced by IR may induce changes in proximal tubule ATPases and RAAS components compatible with renal Na + retention and hypertension. These data also indicate that the NADPH oxidase represents a key factor in the origin of these alterations., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Coronavirus disease 2019 (COVID-19) has affected more than 6 million patients worldwide. Deep venous thrombosis (DVT) has been increasingly recognized complication in these patients and is associated with increased morbidity and mortality. However, the factors associated with development of DVT in patients with COVID-19 have not been elucidated due to the novelty of the virus. We performed a meta-analysis of published studies comparing laboratory results in COVID-19 patients with and without DVT with the aim of identifying risk factors. We searched major databases for studies evaluating DVT in COVID-positive patients and performed a meta-analysis of baseline laboratory markers associated with development of DVT. A total of six studies with 678 patients were included in the pooled analyses. Of the 678 patients, 205 of patients had a DVT. Patients diagnosed with DVT were more likely to be older [mean difference 4.59 years, 95% confidence interval (CI) 1.25-7.92], and needing admission to ICU (relative risk 1.96, 95% CI 1.09-3.51). Patients with DVT had significantly higher white cell count (mean difference 1.36 × 109/l, 95% CI 0.33-2.40) and d-dimer levels (mean difference 3229.8, 95% CI 1501.5-4958.1). Lymphocyte count was lower in patients with DVT (mean difference -0.19 × 109/l, 95% CI -0.37 to -0.02). Patients with COVID-19 who develop DVT are more likely to be older and have leukocytosis with lymphopenia. Moreover, d-dimer is statistically higher and patients that are admitted to the ICU are at great risk to develop DVT., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Lenticulostriate artery aneurysms (LSAs) are rare vascular aberrations. Despite the potentially catastrophic sequelae of aneurysmal rupture, the optimal management strategy for LSA aneurysms has not been determined. The aim of the present review is to provide an overview of the clinical presentation and treatment strategies for LSA aneurysms., Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a literature search was conducted in the PubMed, Cochrane, EBSCOhost, Scopus, Web of Science, and ProQuest search engines to identify reported studies of LSA aneurysms until July 1, 2020. A descriptive analysis was performed., Results: A total of 71 studies with 112 cases of LSA aneurysms were included. Patient age ranged from 2 months to 83 years (median, 44.5 years). Male and female patients were affected similarly (49% and 51%, respectively). The most common presentation was aneurysmal rupture (78%), and headache was the most frequently reported symptom (36%). Overall, 48% of the patients had undergone underwent surgical treatment, 30% conservative management, 21% endovascular treatment, and 1% radiosurgery. Four patients died, all of whom had presented with aneurysmal rupture., Conclusion: We have summarized the reported cases of LSA aneurysms, with their clinical presentation, management, and outcomes, for physicians who may be confronted with this diagnosis. Future studies that use available classification systems and include as much detail as possible should be encouraged to fully elucidate the optimal management strategy for these patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Intensive care has played a pivotal role during the COVID-19 pandemic as many patients developed severe pulmonary complications. The availability of information in pediatric intensive care units (PICUs) remains limited. The purpose of this study is to characterize COVID-19 positive admissions (CPAs) in the United States and to determine factors that may impact those admissions., Materials and Methods: This is a retrospective cohort study using data from the COVID-19 Virtual Pediatric System (VPS) dashboard containing information regarding respiratory support and comorbidities for all CPAs between March and April 2020. The state-level data contained 13 different factors from population density, comorbid conditions, and social distancing score. The absolute CPA count was converted to frequency using the state's population. Univariate and multivariate regression analyses were performed to assess the association between CPA frequency and admission endpoints., Results: A total of 205 CPAs were reported by 167 PICUs across 48 states. The estimated CPA frequency was 2.8 per million children in a one-month period. A total of 3,235 tests were conducted of which 6.3% were positive. Children above 11 years of age comprised 69.7% of the total cohort and 35.1% had moderated or severe comorbidities. The median duration of a CPA was 4.9 days (1.25-12.00 days). Out of the 1,132 total CPA days, 592 (52.2%) involved mechanical ventilation. The inpatient mortalities were 3 (1.4%). Multivariate analyses demonstrated an association between CPAs with greater population density (beta coefficient 0.01, p < 0.01). Multivariate analyses also demonstrated an association between pediatric type 1 diabetes mellitus with increased CPA duration requiring advanced respiratory support (beta coefficient 5.1, p < 0.01) and intubation (beta coefficient 4.6, p < 0.01)., Conclusions: Inpatient mortality during PICU CPAs is relatively low at 1.4%. CPA frequency seems to be impacted by population density. Type 1 DM appears to be associated with increased duration of HFNC and intubation. These factors should be included in future studies using patient-level data., Competing Interests: The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2020 Rohit S. Loomba et al.)

Maternal endotoxemia has been shown to increase renal collagen deposition in the offspring. Renal fibrosis is a hallmark of progressive chronic kidney disease. It was investigated whether maternal reactive oxygen species (ROS) leads to renal fibrosis or exacerbates unilateral ureteral obstruction (UUO)-induced renal fibrosis in the offspring of dams treated with lipopolysaccharide (LPS). Furthermore, it was studied the role of matrix metalloproteinases (MMPs) in these changes. Adults Wistar rats were obtained from dams submitted to LPS administration through the third part of gestation. To evaluate the role of maternal ROS, part of the dams received α-tocopherol simultaneously with LPS. Part of the offspring in each group was submitted to UUO at adulthood when sub-groups were treated with NADPH oxidase inhibitor, apocynin. Maternal LPS administration increased proteinuria, systolic arterial pressure and renal collagen deposition in adult offspring. LPS offspring rats also presented higher MMP-2 activity in parallel to a decreased renal cortical TIMP-2 content. These changes were correlated to increased amounts of TGF-β1 and NOX2. Maternal α-tocopherol treatment prevented collagen deposition and reduced arterial pressure in adult offspring. α-Tocopherol also inhibited maternal endotoxemia-induced changes in TGF-β1/NOX2/MMP-2 signaling. UUO led to increased collagen deposition in the contralateral kidneys of LPS offspring, which was correlated to increased NADPH oxidase activity and prevented by NADPH oxidase inhibition. In summary, maternal endotoxemia led to alterations in the TGF-β1/NOX2/MMP-2 signaling pathway in renal tissue concomitant with collagen deposition, therefore contributing to hypertension in adult offspring., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

NPCdc is a synthetic natriuretic peptide that was originally derived from another peptide, the NP2&#95;Casca, isolated from Crotalus durissus cascavella venom. These molecules share 70% structural homology with natriuretic peptides obtained from different species, including humans. NP2&#95;Casca induces vasorelaxation and increases nitric oxide levels independently of natriuretic peptide receptors A and B. This study aimed to investigate whether NPCdc-induced hypotension in control rats and rats with a reduced kidney mass is associated with effects on the glomerular filtration rate, NADPH oxidase activity and components downstream of natriuretic peptide receptor C (NPR-C). Anaesthetized Wistar rats that were subjected to a sham operation and 5/6 nephrectomy (5/6Nx) were infused with saline (vehicle) or NPCdc (7.5 μg/kg/min) for 70 min. The NPCdc treatment decreased the mean arterial pressure and NADPH oxidase activity while simultaneously increasing the glomerular filtration rate, fractional Na + excretion and nitric oxide level. After 70 min, the levels of p-AKT Ser-473 , p-eNOS Ser-1177 , p-nNOS Ser-1417 and p-iNOS Tyr-151 were not affected. However, p-ERK1/2 Thr-202/Tyr-204 levels were altered. Thus, nitric oxide and components of NPR-C signalling mediate the effects of NPCdc. The results suggest a potential therapeutic application of this peptide for cardiorenal syndrome., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Maternal salt overload programs cardiovascular and renal alterations in the offspring. However, beneficial and harmful effects of high dose vitamin E supplementation have been described in humans and animals. We investigated the hypothesis as to whether cardiac and renal alterations can be programmed by gestational salt overload, and can become further modified during lactation and after weaning. Male Wistar rats were used, being the offspring of mothers that drank either tap water or 0.3 mol/L NaCl for 20 days before and during pregnancy. α-Tocopherol (0.35 g/kg) was administered to mothers daily during lactation or to their offspring for 3 weeks post-weaning. Systolic blood pressure (tcSBP) was measured in juvenile rats aged 210 days. The response of mean arterial pressure (MAP) and heart rate (HR) to intravenous infusion of angiotensin II (Ang II) was also examined. Left ventricle plasma membrane (PMCA) and sarcoplasmic reticulum Ca 2+ -ATPase (SERCA) activities, and certain parameters of renal function, were measured. Maternal saline programmed for increased body mass and kidney mass/body mass ratio, increased tcSBP, increased mean arterial pressure and heart rate with anomalous response to infused Ang II. In the heart, saline increased PMCA and α-Tocopherol per se increased PMCA/SERCA. In the kidney, the most remarkable result was the silent saline programming of Cr Cl , which was sensitized for a sharp decrease after α-Tocopherol. In conclusion, the combination of maternal saline overload and high α-Tocopherol immediately after birth leads to simultaneous cardiovascular and renal alterations in the young offspring, like those encountered in type V cardiorenal syndrome., (© 2019 John Wiley & Sons Australia, Ltd.)

Ethnomedicinal studies in the Amazon community and in the Northeast region of Brazil highlight the use of Libidibia ferrea fruits for the treatment of gastric problems. However, there are no data in the literature of this pharmacological activity. Thus, the aim of this paper is to provide a scientific basis for the use of the dry extract of L. ferrea pods (DELfp) for the treatment of peptic ulcers. Phytochemical characterization was performed by HPLC/MS. In vitro antioxidant activity was assessed using DPPH, ABTS, phosphomolybdenum, and superoxide radical scavenging activity. The gastroprotective activity, the ability to stimulate mucus production, the antisecretory activity, and the influence of -SH and NO compounds on the antiulcerogenic activity of DELfp were evaluated. The healing activity was determined by the acetic acid-induced chronic ulcer model. Anti- Helicobacter pylori activity was investigated. HPLC/MS results identified the presence of phenolic compounds, gallic acid and ellagic acid, in DELfp. The extract showed antioxidant activity in vitro . In ulcers induced by absolute ethanol and acidified ethanol, the ED 50 values of DELfp were 113 and 185.7 mg/kg, respectively. DELfp (100, 200, and 400 mg/kg) inhibited indomethacin-induced lesions by 66.7, 69.6, and 65.8%, respectively. DELfp (200 mg/kg) reduced gastric secretion and H + concentration in the gastric contents and showed to be independent of nitric oxide (NO) and dependent on sulfhydryl (-SH) compounds in the protection of the gastric mucosa. In the chronic ulcer model, DELfp reduced the area of the gastric lesion. DELfp also showed anti- H. pylori activity. In conclusion, DELfp showed antioxidant, gastroprotective, healing, and antiulcerogenic activities. The mechanism of these actions seems to be mediated by different pathways and involves the reduction of gastric secretion and H + concentration, dependence on sulfhydryl compounds, and anti- H. pylori activity. All these actions support the medicinal use of this species in the management of peptic ulcers., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2019 Lady D. K. T. Prazeres et al.)