Assessment of the perceived burden associated with Malignant Melanoma with Pictorial Representation of Illness and Self Measure (PRISM) and Melanoma Concerns Questionnaire (MCQ-28)

Purpose The impact of malignant melanoma (MM) on patients’ psychophysical well-being has been poorly addressed. We aimed to assess the perceived burden in patients with a diagnosis of MM, using two different tools, one generic and one specific for MM, such as Pictorial Representation of Illness and Self Measure (PRISM) and Melanoma Concerns Questionnaire (MCQ-28), respectively. The correlation between PRISM and MCQ-28 subscales and the relevance of disease and patient-related variables were also investigated. Methods This single-centre, cross-sectional study included all adult consecutive MM patients who attended our Dermatology Unit from December 2020 to June 2021. Demographics and disease-related data were recorded. PRISM and MCQ-28 were administered. Results One hundred and seventy-one patients were included (mean age: 59.5 ±14.9 years.; 48.0% males). Median time from MM diagnosis to inclusion was 36 months. Nearly 80% of the patients had in situ or stage I MM. Overall, 22.2% of the patients reported a PRISM score <100mm and similar percentages provided scores indicating impaired quality of life, as assessed with MCQ-28 subscales. A weak, albeit significant, correlation was found between PRISM scores and ACP, CON and SOC2 subscales. The most relevant association found was that between lower PRISM scores and higher-stage MM. Conclusions In the study population, mostly affected with superficial MM, their perception of the burden associated with MM did not appear either particularly dramatic or disabling. PRISM seems a reliable system for capturing and quantifying the domains correlated with the emotive dimension of MM, especially MM-related concerns and willingness to face life

1140. Impact of a Rapid Molecular Bloodstream Diagnostic Test on Optimal Antibiotic Use in Infants

Background Rapid molecular bloodstream diagnostics have been shown to decrease time-to-optimal antibiotic therapy in adult and pediatric patients. The purpose of the study was to compare the time-to-optimal antimicrobial therapy both pre-and post- implementation of rapid diagnostic testing in infants. Methods This was a single-center quasi-experimental study conducted from December 2018 to December 2020 at Children’s Hospital New Orleans. A rapid, multiplex polymerase chain reaction bloodstream diagnostic was implemented in January 2019. Antimicrobial Stewardship performed a daily review of all antimicrobials during both periods and made recommendations when necessary. The primary outcome was the difference in time-to-optimal therapy. Secondary outcomes included time-to-effective therapy, 30-day all-cause mortality rate, 30-day recurrent bacteremia rate, and time-to-microbiologic clearance. Patients were excluded if they had an unrelated concomitant infection, withdrawal of care before the result, bacteria not identified by the panel, or were over 6 months of age. Results Thirty-five and forty-three patients met inclusion criteria pre-and post-implementation. The median post-natal age was 2 months and median PRISM score was 12 in both groups. Median time-to-optimal therapy was 53.1 hours in the pre-intervention and 24.4 hours in the post-intervention group (-28.7 hours, P = 0.03). Median time-to-effective therapy was 0 and 1.4 hours, respectively (+1.4 hours, P = 0.02). There was no significant difference in 30-day all-cause mortality (3 vs. 4 patients, P = 0.62), 30-day recurrent bacteremia (0 vs. 2 patients, P = 0.2), or microbiologic clearance (37.3 vs. 26.2 hours, P = 0.09). Conclusion Implementation of a rapid, multiplex bloodstream diagnostic lead to a significant decrease in time-to-optimal antibiotic therapy in infants when compared to standard microbiological techniques. Disclosures All Authors: No reported disclosures

939. Predicting Attributable Mortality in Pediatric Patients with Cancer Admitted to the Intensive Care Unit for Suspected Infection

Background Infection and sepsis are important contributors to mortality in children with cancer. Although pediatric risk prediction scores have improved identification of children at high risk of death in the PICU, the value of these tests in immunocompromised children is unknown. Methods In this IRB-approved retrospective study performed at St. Jude Children’s Research Hospital, we evaluated the performance of 4 pediatric risk scores, the Pediatric Risk of Mortality (PRISM), Pediatric Sequential Organ Failure Assessment (pSOFA), Quick Sequential Organ Failure Assessment (qSOFA) scores (using data available at 1, 6, 12 and 24 hours) and the Paediatric Index of Mortality 3 (PIM-3) score (at 1 hour), to predict attributable mortality (death ≤ 60 days without organ dysfunction recovery). Inclusion criteria: Age &lt; 24 years, active cancer therapy (other than bone marrow transplantation), and admission to PICU between 2013 and 2019 with suspected infection (collection of a blood culture and initiation of antibiotic therapy). Scores were calculated using the worst value obtained for each variable. Score distributions were compared by the Mann-Whitney U test, and optimal cutoffs selected by maximizing Youden’s index. An unadjusted p-value &lt; 0.05 was considered statistically significant. Results Of 202 episodes of PICU admission for suspected infection in 168 participants, there were 12 attributable (6%) and 4 unrelated (2%) deaths. Demographic and cancer-related characteristics were not associated with mortality (Table 1). Of the 4 prediction scores, only the PRISM score at 24 hours was associated with mortality (P = 0.012; Table 2). For PRISM score ≥ 18, sensitivity was 58.3%, specificity was 81.6%, positive predictive value was 16.7%, and negative predictive value was 96.9% for attributable mortality. Table 1. Risk factors for attributable mortality in pediatric patients with cancer admitted to the intensive care unit with suspected infection. Table 2. Association between risk prediction scores and attributable mortality in pediatric patients with cancer admitted to the intensive care unit with suspected infection. Conclusion In children with cancer admitted to PICU with suspected infection, early pediatric risk prediction scores did not predict mortality. The PRISM score calculated at 24 hours did predict mortality but was relatively insensitive. Further research is needed to develop a risk score for immunocompromised children and to validate the 24 hour PRISM score in this population. Disclosures Joshua Wolf, MBBS, PhD, FRACP, Karius Inc. (Research Grant or Support) Joshua Wolf, MBBS, PhD, FRACP, Nothing to disclose

Comparison of PICU Cost and Severity-Adjusted Cost Between Patients With SIRS-Defined Sepsis and Those With Age-Adapted SOFA-Defined Sepsis

Background: The 2005 International Pediatric Sepsis Consensus definition is considered to lack specificity and may lead to the admission of low-risk patients to the pediatric intensive care unit (PICU). The aim of this study was to compare the PICU cost and the severity-adjusted cost between patients with sepsis defined by the 2005 International Pediatric Sepsis Consensus and those diagnosed using the age-adapted Sepsis-3 criteria.Methods: Septic children identified by the 2005 Consensus were screened for enrollment. The enrolled children were stratified into two subgroups using the age-adapted Sepsis 3.0 definition. A comparison was made between the subgroups of sepsis 3.0-defined children and non-sepsis 3.0-defined septic children. The Severity Adjusted ICU Cost (SAIC) was used to evaluate the case-mixed severity-adjusted costs of the study population. Coefficients in linear regression analyses in subgroups were calculated for presenting variation of PICU costs for every unit change of PRISM score.Results: A total of 397 children were enrolled. The PICU length of stay was longer in the sepsis 3.0 group than in the non-sepsis 3.0 group [median (IQR), 9.0 (5.0, 15.0) vs. 6.0 (3.0, 9.0); P &lt; 0.001]. Pediatric risk of mortality (PRISM) scores and mortality were significantly higher in sepsis 3.0-defined septic patients. The total costs and daily costs in the PICU were both significantly lower in the non-sepsis 3.0 group (P &lt; 0.001). The severity-adjusted ICU cost in the non-sepsis 3.0 group was lower than that in the sepsis 3.0 group [median (IQR), 7,125 (3,588, 11,134) vs. 9,364 (5,680, 15,876); P = 0.001]. There was no significant difference among the regression coefficients.Conclusions: The 2005 International Pediatric Sepsis Consensus definition does not lead to more PICU costs after considering illness severity.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03598127.

“LACTATE CLEARANCE IS PREDICTOR OF MORTALITY IN CRITICALLY ILL CHILDREN”

Background and Objectives: High lactate level in blood (hyperlactatemia) is a frequent phenomenon in critically ill children which carries signicant prognostic value. However, a single lactate value is a static variable and can only serve as a risk-stratication biomarker and such a “high” level is not well dened. Studies have conrmed that serial measurements of lactate or lactate clearance (LC) over time serve as better prognosticators of organ failure and mortality. In the present study, we studied the role of lactate clearance in early period of resuscitation (rst 8 hours of hospitalization) in mortality prediction. This prospective observational st Methodology: udy was conducted over 1 years from April 2019- March 2020 including Children aged >1 month and <15 years admitted to PICU of our hospital. Lactate level estimation was done on admission and after 8 hours of treatment for calculation of lactate clearance. Over the Results: study period, we enrolled 52 children in our study. Mean age was 4.3 years (SD 1.9 years), male: female ratio was 1.26: 1 (29 males, 23 females). Mortality was 14 (26.9%) in the study population. There was no statistically signicant difference in the initial lactate level in those who survived vs those who died (p=0.19). However, there was a statistically signicantly lower lactate in survivors at 8 hours as compared to non survivors (p <0.0001). Lactate clearance at 8 hours was also signicantly lower in those who died (5.85%) than those who survived (51.2%) (P=0.001). Lactate clearance <30% at 8 hours had a sensitivity of 71.4% and specicity of 94.7% in mortality prediction. Mean PRISM score was also signicantly higher in non survivors as compared to those who survived (P<0.0001). We also found an inverse relationship between lactate clearance and PRISM score Lactate clearance <30% at 8 hours and Conclusion: PRISM III score more than 30 are predictive of mortality in critically ill children

Abstract 14066: O -GlcNAc Levels Stimulation is a New Potential Therapeutic Strategy at the Early Phase of Septic Shock in the Young

Background: We have shown that increase in O -GlcNAc levels, a post-translational modification involved in the stress response, at the early phase of septic shock in adult (84 days old rats) is a potential new therapeutic strategy. Most studies focus in adults while the population most affected by septic shock, young children, is rarely studied. Considering that O- GlcNAc levels are higher in the young, the impact of O- GlcNAc on septic shock in the young should be tested. Purpose: Evaluate if O- GlcNAc stimulation could improve sepsis outcomes in young. Methods: Endotoxemic shock was induced in 28 days old rats with an i.v. injection of saline (CTRL, n=10) or LPS (O111:B4, 20mg.kg -1 - LPS, n=9). 1 hour after LPS rats were randomly assigned to no therapy (LPS), fluidotherapy (saline, 10ml.kg -1 - LPS+R, n=10) ± NButGT (10 mg.kg -1 - NButGT, n=11) to increase O- GlcNAc levels. 2 hours later, physiological functions and markers of severity were measured and used in adapted Pediatric RISk of Mortality score (PRISM score). The impact of treatment on survival was evaluated on n=16 per group. Mass spectrometry (MS) study was performed to identify O -GlcNAcylated proteins. Results: LPS induce a shock (mean arterial pressure (MAP): CTRL: 67.2 ± 1.9; LPS: 50.7 ± 2.1; mmHg; p<0.05), alter biological parameters (lactates: CTRL: 3.92 ± 0.26; LPS: 6.42 ± 0.45; mmol.l -1 ; pH: CTRL: 7.27 ± 0.02; LPS: 7.15 ± 0.02; p<0.05), PRISM score (p<0.05) and is associated with multi organs dysfunction (troponin T: CTRL: 19.7 ± 4.0; LPS: 45.4 ± 11.4; ng.l -1 ; creatinine: CTRL: 15.9 ± 1.5; LPS: 25.3 ± 2.6; μmol.l -1 ; p<0.05). LPS+R has no beneficial effect while NButGT improves MAP (p<0.05), PRISM score (p<0.05) and the median survival (NButGT: 36.0; LPS+R: 13.65; hours; p<0.001) compared to LPS+R treatment. MS highlight important variations of O- GlcNAcylation particularly that of mitochondrial proteins. Conclusions: Despite higher O- GlcNAc levels, we demonstrate that O- GlcNAc stimulation is also a potential new therapeutic strategy for septic shock in young. Our results show that it is the difference between the basal levels and the post-stimulation levels which induces a protection against sepsis. Proteins identify by MS will need to be specifically studied to decipher their impact in septic shock.

Abnormal Metaphase Cytogenetics Adds to Currently Known Risk-Factors for Venous Thromboembolism in Multiple Myeloma: Derivation of the PRISM score

Background: Prevention and management of venous thromboembolic events [VTE] is an important component of supportive care in newly diagnosed multiple myeloma [MM], especially in the era of immunomodulatory drugs [IMiDs]. Recently, two validated risk assessment models [RAMs], SAVED and IMPEDE-VTE, were developed to identify patients at high risk of VTE. However, these models have following limitations: (1) Patients were not uniformly treated in the era of contemporary MM therapy (2) Disease-specific variables were not available in the databases from which these scores were derived. Our primary aim was to develop a simple predictive model for VTE in MM using patient-specific, disease-specific, and treatment-specific variables. Our secondary aim was to assess the impact of VTE on overall survival [OS]. Methods: All consecutive patients with newly diagnosed MM treated at Cleveland Clinic from 1/1/2008 to 12/31/2018 were included in our analysis. The primary objective was to identify baseline variables associated with VTE within 12 months of treatment initiation. Candidate variables included those in IMWG, SAVED, and IMPEDE-VTE models as well as additional risk-factors from literature review in MM and cancer-associated VTE. Stepwise selection with variable entry criterion of p&lt;0.20 and a variable retention criterion of p&lt;0.05 was used to identify significant factors on multivariable analysis [MVA]. RAM was developed by subtracting 1 from the hazard ratio of a potential variable, rounding to the nearest 0.5, and multiplying by 2 to obtain a whole number. The impact of VTE on OS was assessed with landmark analysis. Results: A total of 934 patients with newly diagnosed MM and available data on VTE occurrence were considered for inclusion. We excluded patients with VTE within 6 months before starting therapy [n=5] and patients on therapeutic anticoagulation or receiving &gt;1 prophylactic regimen [n=146], resulting in a total of 783 patients for model development. The most common induction regimen was bortezomib [V]-lenalidomide [R]-dexamethasone [VRD; 41%], followed by VD [22%], RD [20%], V-cyclophosphamide-dexamethasone [VCD; 11%], and others [7%]. Median age at treatment initiation was 63 years [range, 22-91], 55% were males, and 20% were Blacks. ISS stage III disease was present in 32%, high-risk FISH in 23%, abnormal metaphase cytogenetics in 18%, and serum creatinine &gt;2 mg/dl in 19% of patients. Notably, 76% had received a dexamethasone dose of 120-160 mg/cycle, with only 5.9% started on a higher dose [&gt;160 mg/cycle]. The most common thromboprophylaxis agent was aspirin [60%], followed by low molecular weight heparin [LMWH; 3.8%]; 37% of patients received no thromboprophylaxis. Erythropoietin and intravenous immunoglobulin were used in 2.9% and 1.2% of patients respectively. Median time to VTE from treatment initiation was 3.2 months. Cumulative incidence of VTE at 6 and 12 months was 8.2% [95% CI, 6.6-10.1] and 11.5% [95% CI, 9.5-13.6] respectively. Factors significantly associated with development of VTE on MVA were combined to develop the PRISM score [Table 1]: Prior VTE history [HR 5.06; 8 points], Black Race [HR 1.71; 1 point], IMiD use [HR 2.17; 2 points], Surgery within 3 months [HR 3.44; 5 points], and abnormal Metaphase cytogenetics [HR 2.10; 2 points]. The theoretical score range is 0-18, with a HR of 1.28 per 1-point increase in score [c-statistic 0.62]. Internal bootstrap validation including 1,000 samples showed a c-statistic of 0.62 [IQR, 0.60-0.64]. Using three risk groups by recursive partitioning analysis, 17.8%, 74%, and 8.1% belonged to low [0], intermediate [1-6], and high-risk [&gt;6] groups respectively. The 12-month cumulative incidence of VTE in the 3 respective groups were 2.7%, 10.8%, and 36.5% [Figure 1]. Occurrence of VTE in the first 12 months was not associated with worse OS on landmark analysis at 3, 6, 9, and 12 months. Conclusion: We have developed and internally validated a RAM for VTE in MM in the context of contemporary MM therapy including disease-specific variables. Studies of external validation and comparison with existing RAMs are warranted. The PRISM Score could be used to identify high-risk patients for thromboprophylaxis. Figure Disclosures Valent: Amgen Inc.: Other: Teaching, Speakers Bureau; Takeda Pharmaceuticals: Other: Teaching, Speakers Bureau; Celgene: Other: Teaching, Speakers Bureau. Khouri:Sanofi Genzyme: Other: Advisory Board. Anwer:Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau. Khorana:Pharmacyclics: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; Medscape: Honoraria; Leo Pharma: Honoraria; Seattle Genetics: Honoraria; Pharmacyte: Honoraria; Leap: Research Funding; Bayer: Honoraria; Janssen: Honoraria; Merck: Research Funding; Array: Other: Research funding (to institution); BMS: Honoraria, Research Funding.

Arterial Blood Lactate in Children Primarily Submitted to Noninvasive Ventilation: A Time-Dependent ROC Analysis

The purpose of this study was to evaluate blood lactate measurements and failure to noninvasive ventilation (NIV) in children admitted to a pediatric intensive care unit. This was a retrospective observational single-center study performed between June 2016 and June 2017. Dynamic lactate indices and failure to NIV in 63 children < 18 years and > 1 month old were examined; we considered blood lactate analyses at time 0, 6, 24, and 48 hours. NIV failure group had a higher pediatric risk of mortality (PRISM) score. Lactate indices decreased over time in the success group (p < 0.001). The best area under the curve observed was 69%, at 48 hours. Considering all measurements, the area under the curve for time-dependent receiver-operating characteristic curve was 58.6%. This study demonstrated blood lactate indices evolution over time in children submitted to NIV.

Prediction of the risk of mortality in paediatric intensive care unit using PRISM III score

Background: is the Pediatric risk of mortality (PRISM) score which has been devised by Pollock et al, to predict the mortality in hospitalized children. PRISM score is a revised form of physiologic stability index of mortality score.Methods: A observational prospective study was conducted at tertiary care hospital, Udaipur Rajasthan over period of March 2017 to September 2018. Total 207 patient were enrolled in study as per inclusion and exclusion criteria.Results: Total 29.92% had PRISM III score of 0 to 5, 25.45% had score of 6-10, 16.53% had score of 11-15, 13.12% had score of 16-20, 7.61% between 21 to 25, 4.72% between 26-30 and 2.62% had score of greater than 30. There was no mortality when the PRISM score of the child was between 0 to 5. The percentage of deaths increased progressively with increasing PRISM score.Conclusions: There was no significance difference in predicted from PRISM score and the actual death. The expected mortality was comparable to actual death, except in children who required mechanical ventilation and vasopressor drugs.