Intensive plasma exchange in small and critically ill pediatric patients: Techniques and clinical outcome

1983 ◽  
Vol 1 (4) ◽  
pp. 215-224 ◽  
Author(s):  
Martin Fosburg ◽  
Mary Dolan ◽  
Richard Propper ◽  
Lawrence Wolfe ◽  
Sherwin Kevy
Keyword(s):  
Clinical Outcome ◽  
Plasma Exchange ◽  
Critically Ill ◽  
Pediatric Patients

scholarly journals Sars-Cov-2 Induced Endotheliopathy and the Impact on Clinical Outcomes in Critically Ill Pediatric Patients

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3145-3145
Author(s):  
Shreya Agarwal ◽  
Mark Zobeck ◽  
Clay T Cohen ◽  
Sarah E Sartain
Keyword(s):  
Mechanical Ventilation ◽  
Statistical Analysis ◽  
Clinical Outcome ◽  
Clinical Outcomes ◽  
Critically Ill ◽  
Pediatric Patients ◽  
Endothelial Injury ◽  
Negative Regulator ◽  
Plasma Samples ◽  
Positive Correlation

Abstract Background: Coronavirus disease-19 (COVID-19) is an acute respiratory illness caused by the SARS-COV-2 virus. Patients with COVID-19 infection can present with thrombosis in the setting of inflammation (thromboinflammation), presumably from endothelial dysfunction, or "endotheliopathy". Yu et al demonstrated in vitro that the spike protein subunit of SARS-COV2 acts as a potent activator of the alternative complement pathway (AP), one of three complement pathways within the innate immune system. Satyam et alreported the deposition of complement components on lung tissue of patients who succumbed to COVID-19, consistent with activation of classical and alternate pathways. These studies suggest complement dysregulation potentially causing endotheliopathy in COVID-19 patients. Thrombomodulin (TM) is an endothelial glycoprotein that plays two crucial roles in maintaining a healthy endothelium - as a natural anticoagulant and a negative regulator of complement. TM shed into the circulation due to endothelial injury can be measured in the plasma as soluble TM (sTM). Goshua et al showed elevated sTM in an adult cohort of patients with COVID-19. However, it is yet to be demonstrated if there is any correlation between endothelial injury and AP activation in COVID-19, or if either play a role in clinical outcome in the pediatric population. Objective: To 1) assess endothelial injury and AP activation in a cohort of critically ill pediatric patients with COVID-19 by measuring sTM and Ba (an AP activation product); 2) determine the correlation between endothelial injury and AP activation; and 3) analyze the utility of sTM and Ba in predicting pediatric clinical outcomes. Methods: We collected plasma samples of patients admitted to the Pediatric Intensive Care Unit and found to be positive for SARS-CoV-2 between Dec 2, 2020 and Jan 22, 2021 at Texas Children's Hospital. For controls, we collected plasma samples from pediatric patients undergoing preoperative clearance, all at their baseline state of health. sTM levels and Ba levels were measured in plasma samples using commercially available TM and Ba ELISA kits. sTM greater than 7.6 ng/ml (based on the assay range in adults) and Ba greater than 1080 ng/ml (based on data from adult healthy controls) were considered elevated. Data regarding demographics, length of ICU stay, clinical indicators of end organ damage- mechanical ventilation, dialysis, use of vasopressors, ECMO, mortality were obtained retrospectively via chart review. Inclusion criteria included all patients with a positive SARS-COV2 PCR admitted to the ICU. Exclusion criteria was age greater than 21 years, pregnant female, patients with known inflammatory or complement-mediated disorders. Statistical analysis: For sTM and Ba levels between control and COVID-19 patients, mean +/- standard deviation was calculated and significance determined with an unpaired t-test. Fischer exact test, Wilcoxon rank sum and Pearson product-moment correlation tests were used for statistical analysis of clinical outcomes as appropriate. A p-value <0.05 was considered statistically significant. Results: A total of 38 control patients and 33 COVID-19 patients were enrolled. Ba and sTM levels were both significantly higher in the COVID-19 pediatric patients compared to the controls (Fig. 1). Within the COVID-19 patient cohort, 61% (n=20) had elevated sTM and 42% (n=14) had elevated Ba levels. There was a moderately positive correlation between sTM and plasma Ba levels in the COVID-19 cohort (Fig. 2). Within the COVID-19 patients' cohort, though higher Ba levels were not associated with an increased rate of intubation, they were associated with an increased duration of mechanical ventilation (p=.039) for those intubated (Table 1). Elevated sTM was associated with increased vasopressor use (p=.011). Although other clinical outcome variables did not reach statistical significance likely owing to small numbers, overall trend indicated worse outcomes in patients with elevated sTM. Conclusions: Our findings are consistent with the hypothesis that SARS-COV-2 activates AP and causes endothelial injury in children. The positive correlation between sTM and Ba suggest interplay between inflammation, coagulation and endotheliopathy supporting thromboinflammation in COVID-19. Higher sTM and Ba levels indicated worse clinical outcomes in children, but larger studies are needed to confirm our findings. Figure 1 Figure 1. Disclosures Sartain: Alexon Pharamaceuticals: Membership on an entity's Board of Directors or advisory committees.

Therapeutic Plasma Exchange Application in Children Requires Individual Decision

2020 ◽  
Author(s):  
Gürkan Atay ◽  
Demet Demirkol
Keyword(s):  
Plasma Exchange ◽  
Vascular Access ◽  
Pediatric Patients ◽  
Demyelinating Disease ◽  
Pediatric Intensive Care ◽  
Therapeutic Plasma Exchange ◽  
Transplantation Rejection ◽  
Access Problems ◽  
Uremic Syndrome

AbstractTherapeutic plasma exchange (TPE) is a treatment administered with the aim of removing a pathogenic material or compound causing morbidity in a variety of neurologic, hematologic, renal, and autoimmune diseases. In this study, we aimed to assess the indications, efficacy, reliability, complications, and treatment response of pediatric patients for TPE. This retrospective study analyzed data from 39 patients aged from 0 to 18 years who underwent a total of 172 TPE sessions from January 2015 to April 2018 in a tertiary pediatric intensive care unit. Indications for TPE were, in order of frequency, macrophage activation syndrome (28.2%, n = 11), renal transplantation rejection (15.4%, n = 6), liver failure (15.4%, n = 6), Guillain–Barre's syndrome (15%, n = 6), hemolytic uremic syndrome (7.7%, n = 3), acute demyelinating disease (7.7%, n = 3), septic shock (5.1%, n = 2), and intoxication (5.1%, n = 2). No patient had any adverse event related to the TPE during the procedure. The TPE session was ended prematurely in one patient due to insufficient vascular access and lack of blood flow (2.6%). In the long term, thrombosis due to the indwelling central catheter occurred (5.1%, n = 2). TPE appears to be an effective first-stage or supplementary treatment in a variety of diseases, may be safely used in pediatric patients, and there are significant findings that its area of use will increase. In experienced hands and when assessed carefully, it appears that the rate of adverse reactions and vascular access problems may be low enough to be negligible.

Mapping efficacious deep brain stimulation for pediatric dystonia

2021 ◽  
pp. 1-11
Author(s):  
Ailish Coblentz ◽  
Gavin J. B. Elias ◽  
Alexandre Boutet ◽  
Jurgen Germann ◽  
Musleh Algarni ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Clinical Outcome ◽  
Brain Stimulation ◽  
Pediatric Patients ◽  
Rating Scale ◽  
Structural Connectivity ◽  
Response To Treatment ◽  
Internal Globus Pallidus ◽  
Probabilistic Map ◽  
Deep Brain

OBJECTIVEThe objective of this study was to report the authors’ experience with deep brain stimulation (DBS) of the internal globus pallidus (GPi) as a treatment for pediatric dystonia, and to elucidate substrates underlying clinical outcome using state-of-the-art neuroimaging techniques.METHODSA retrospective analysis was conducted in 11 pediatric patients (6 girls and 5 boys, mean age 12 ± 4 years) with medically refractory dystonia who underwent GPi-DBS implantation between June 2009 and September 2017. Using pre- and postoperative MRI, volumes of tissue activated were modeled and weighted by clinical outcome to identify brain regions associated with clinical outcome. Functional and structural networks associated with clinical benefits were also determined using large-scale normative data sets.RESULTSA total of 21 implanted leads were analyzed in 11 patients. The average follow-up duration was 19 ± 20 months (median 5 months). Using a 7-point clinical rating scale, 10 patients showed response to treatment, as defined by scores < 3. The mean improvement in the Burke-Fahn-Marsden Dystonia Rating Scale motor score was 40% ± 23%. The probabilistic map of efficacy showed that the voxel cluster most associated with clinical improvement was located at the posterior aspect of the GPi, comparatively posterior and superior to the coordinates of the classic GPi target. Strong functional and structural connectivity was evident between the probabilistic map and areas such as the precentral and postcentral gyri, parietooccipital cortex, and brainstem.CONCLUSIONSThis study reported on a series of pediatric patients with dystonia in whom GPi-DBS resulted in variable clinical benefit and described a clinically favorable stimulation site for this cohort, as well as its structural and functional connectivity. This information could be valuable for improving surgical planning, simplifying programming, and further informing disease pathophysiology.

Removal of elevated circulating angiopoietin-2 by plasma exchange – A pilot study in critically ill patients with thrombotic microangiopathy and anti-glomerular basement membrane disease

2010 ◽  
Vol 104 (11) ◽  
pp. 1038-1043 ◽  
Author(s):  
Carsten Hafer ◽  
Jan Kielstein ◽  
Marion Haubitz ◽  
Hermann Haller ◽  
Svjetlana Lovric ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Plasma Exchange ◽  
Critically Ill ◽  
Glomerular Basement Membrane ◽  
Critically Ill Patients ◽  
Plasma Levels ◽  
Vascular Inflammation ◽  
Endothelial Damage ◽  
Healthy Controls ◽  
Angiopoietin 2

SummaryIn critically ill patients, the massive release of angiopoietin-2 (Ang-2) from Weibel-Palade bodies interferes with protective angiopoietin-1 (Ang-1)/Tie2 signalling in endothelial cells, thus leading to vascular inflammation and subsequent organ-dysfunction. We hypothesised that plasma exchange (PE) is efficient for lowering excess Ang-2 levels in critically ill patients with thrombocytic microangiopathy (TMA) or anti-glomerular basement membrane (anti-GBM) disease. Plasma Ang-1 and Ang-2 were measured by immuno-luminometric assays in patients with TMA (n=9) or anti-GBM disease (n=4) before and after up to four PE sessions. Twenty apparently healthy volunteers served as controls. Median (IQR) plasma levels of Ang-2 were markedly increased in patients with TMA (7.3 (2.4–21.1) ng/ml) and anti-GBM disease (5.8 (3.4–7.0) ng/ml) compared to healthy controls (1.0 (0.9–1.4) ng/ml, p <0.001). Moreover, Ang-1 plasma levels were decreased in both, TMA (1.02 (0.62–1.62) ng/ml) and anti-GBM disease patients (0.74 (0.59–3.62) ng/ml) compared to healthy controls (2.5 (1.93–3.47) ng/ ml, p <0.005). During a total of 32 treatments, PE effectively lowered elevated mean (SD) Ang-2 plasma levels by 36.7 ± 19.6 % per treatment (p <0.0001), whereas low Ang-1 plasma levels remained unchanged (0.3 ± 58.5 %; p =0.147). Ang-2 levels declined to almost normal values during ≤4 PE treatments (Friedman´s test p <0.0001). PE is an effective method to remove excess circulating Ang-2. It remains to be elucidated if the removal of Ang-2 is crucial to ameliorate endothelial damage in critically ill patients with severely altered endothelial integrity.

scholarly journals 688 Pediatric Obstructive Sleep Apnea (OSA) and COVID-19-Related Adverse Clinical Outcomes

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A269-A269
Author(s):  
Vaishal Shah ◽  
Nancy Foldvary-Schaefer ◽  
Lu Wang ◽  
Lara Jehi ◽  
Cynthia Pena Obrea ◽  
...  
Keyword(s):  
High Risk ◽  
Clinical Outcome ◽  
Clinical Outcomes ◽  
Pediatric Patients ◽  
Control Design ◽  
Supplemental Oxygen ◽  
Case Control ◽  
World Health ◽  
Invasive Ventilation ◽  
High Flow Oxygen

Abstract Introduction The relationship of OSA and human coronavirus (COVID-19) in the pediatric population is unknown. We postulate that OSA is associated with SARS-CoV-2 positivity and with adverse COVID-19 outcomes in children. Methods A retrospective review of 120 consecutive patients (&lt;18 years) with prior polysomnogram (PSG) and COVID-19 testing from the Cleveland Clinic COVID-19 registry was conducted. Using a case control design of SARS-CoV-2 positive and negative pediatric patients, we examined COVID-19 and pre-existing OSA (dichotomized AHI≥1) using logistic (OR,95%CI) regression and as continuous measures: AHI, oxygen(SpO2) nadir, %time SpO2&lt;90%) using linear regression(beta+/-SE). In those positive for SARS-CoV-2(cases only), we assessed the association of OSA and World Health Organization(WHO) COVID-19 clinical outcome composite score (hospitalization, requiring supplemental oxygen, non-invasive ventilation/high-flow oxygen, invasive ventilation/ECMO or death) using Wilcoxon rank sum test for ordinal data. Results Cases (n=36) were 11.8±4.4 years, 61% male, 27.8% black and 88.9% with OSA, while 85.7% of controls (n=84) had OSA. OSA was not associated with increased SARS-CoV-2 positivity: OR=1.33(0.40, 4.45,p=0.64). No significant difference between cases and controls for mean AHI 3.7(1.5,6.0) vs 3.5(1.5,7.1),p=0.91,SpO2 nadir 88.6±5.4 vs 89.1±4.4,p=0.58,%time SpO2&lt;90% 0.05[0.00,1.00) vs 0.10 (0.00,1.00, p=0.65) respectively was noted. WHO-7 COVID-19 clinical outcome did not meet statistical significance in relation to OSA due to the low event frequency (p=0.49). Of note, those with OSA vs without OSA had a higher WHO-7 outcome score of 2 vs 0 and prevalence of hospitalization: 12.5 vs 0% respectively. Of hospitalized patients, the following was observed: 23% had moderate/severe OSA vs 4.3% mild OSA, 50% required supplemental oxygen and 25% required intubation/invasive ventilation. No deaths or readmissions were reported. High risk conditions included: 75% obesity, 50% asthma, 25% sickle cell disease and 25% hypoplastic left heart. Conclusion In this first report of which we are aware focused on COVID-19 in pediatric OSA, we use a case control design leveraging COVID-19 and sleep laboratory registries. Albeit not statistically significant, pediatric patients with OSA had a higher percentage of worse clinical outcomes. Larger network studies are needed to clarify whether poorer COVID-19 outcomes may be attributable to OSA or modulated via high risk health conditions. Support (if any):

Correlation between oncological family history and clinical outcome in a large monocentric cohort of pediatric patients with rhabdomyosarcoma

2021 ◽  
Author(s):  
Valentina Sottili ◽  
Stefano Signoroni ◽  
Francesco Barretta ◽  
Jacopo Azzollini ◽  
Siranoush Manoukian ◽  
...  
Keyword(s):  
Family History ◽  
Clinical Outcome ◽  
Pediatric Patients
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