scholarly journals 276. SARS-CoV-2 Infection in Solid Organ Transplant Candidates and Recipients at Texas Children’s Hospital: A Retrospective Review

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S243-S244
Author(s):  
Leanne Petters ◽  
Flor M Munoz ◽  
Claire Bocchini ◽  
Elizabeth A Moulton ◽  
Daniel Ruderfer
Keyword(s):  
Research Study ◽  
Organ Transplant ◽  
Scientific Research ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Material Support ◽  
Children's Hospital ◽  
Study Investigator ◽  
Children’S Hospital ◽  
Transplant Candidates

Abstract Background Texas Children’s Hospital (TCH) is the largest pediatric solid organ transplant (SOT) program in the US, performing heart, kidney, liver, and lung transplants. Limited data exists about SARS-CoV-2 infection (COVID-19) in the pediatric SOT populations. We evaluated the impact of COVID-19 in a cohort of PCR positive SOT candidates and recipients. We hypothesized that COVID-19 would more severely impact SOT recipients compared to transplant candidates. Methods Patients with SOT or transplant candidates at TCH with a positive SARS-CoV-2 RT-PCR test since March 1, 2020 to April 12, 2021 were included in the cohort. Retrospective medical record review was performed, and descriptive statistics were used. Results A total of 103 SOT patients were identified, 13 candidates and 90 recipients. Of the SOT candidates, there were 1 heart, 3 kidney, and 9 liver transplant candidates. The SOT recipient cohort included 33 heart, 6 lung, 20 kidney, 33 liver and 2 multi-visceral recipients. A significant difference in age was observed between candidates and recipients with candidates being younger with median age of 4.5 years as opposed to recipient’s median age of 12.8 years (p=0.0003). The majority of patients, 70 of 101 (69%), were symptomatic. Most common symptoms reported were fever in 34/70 (49%), cough in 31/70 (44%), and headache in 19/70 (27%). A higher percentage of candidates (31%, 4 of 13) were hospitalized for acute COVID-19 infection compared to (17%, 15 of 90) of recipients. A transplant candidate who ultimately died from underlying illness and COVID-19 was the only patient in the cohort who required mechanical ventilation. More deaths (2/13, 15%) occurred in transplant candidates with COVID-19 compared to transplant recipients with COVID-19 (1/90, 1%, p=0.04); however, 2 of the deaths occurred after recovery from acute COVID-19 illness. Conclusion Our study suggests that pediatric candidates who are actively listed for transplant with underlying conditions have more severe acute COVID-19 illness than pediatric SOT recipients despite their immunosuppression based on the higher mortality observed in the transplant candidates. Prospective studies are needed to better understand which specific patients are at increased risk for mortality from COVID-19. Disclosures Leanne Petters, MSN, APRN, CPNP-AC, Pfizer (Scientific Research Study Investigator) Flor M. Munoz, MD, Biocryst (Scientific Research Study Investigator)Gilead (Scientific Research Study Investigator)Meissa (Other Financial or Material Support, DSMB)Moderna (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Pfizer (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Virometix (Other Financial or Material Support, DSMB) Elizabeth A. Moulton, MD, PhD, Pfizer (Scientific Research Study Investigator)

scholarly journals 468. Delayed Mortality Among Solid Organ Transplant Recipients Hospitalized for Covid-19: An International Multicenter Study

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S336-S337
Author(s):  
Madeleine R Heldman ◽  
Olivia S Kates ◽  
Robert M Rakita ◽  
Erika D Lease ◽  
Ajit P Limaye ◽  
...  
Keyword(s):  
Risk Factors ◽  
Research Study ◽  
Organ Transplant ◽  
Scientific Research ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Material Support ◽  
Study Investigator ◽  
Solid Organ Transplant Recipients

Abstract Background Studies of solid organ transplant recipients (SOTr) hospitalized for Covid-19 have focused on short-term outcomes with approximately 30 days of follow-up time. Intermediate-term mortality and associated risk factors for intermediate-term death have not previously been reported. Methods Using data from a multi-center registry, we assessed mortality by 90 days among SOTr hospitalized for Covid-19 between 3/1/2020 and 12/31/2020. Multivariable Cox-proportional hazard models were used to compare risk factors for mortality by 28 and 90 days. Covariates were selected a priori based on known predictors of death in SOTr hospitalized for Covid-19. All patients were followed for 90 days or were censored at the time of death or last clinical contact, if this occurred prior to day 90 after diagnosis. Results Among SOTr hospitalized for Covid-19, 198/979 (20%) died within 90 days of diagnosis and 37/198 (19%) of deaths occurred between days 29 and 90. Risk factors for mortality by day 90 days included age >65 years (1.8, 95% CI 1.3-2.4, P< 0.001), lung transplant (compared to non-lung) (1.6, 95% CI 1.1-2.4, P=0.02), chronic lung disease (2.2, 95% CI 1.5-3.4, P=0.002) and heart failure (1.9, 95% CI 1.2-2.9), which were similar to risk factors reported for 28-day mortality (Table 1). Diagnosis during the second half of 2020 (6/20-12/31/20) was associated with lower mortality by 28 days (aHR 0.7, 95% CI 0.5-1.0, P=0.03) compared to diagnosis during the early half of 2020 (3/1-6/19/20); however, mortality by 90 days was similar in the late and early time periods (aHR 0.9, 95% CI 0.7-1.2, P=0.54). Obesity and mTOR inhibitor use were also associated with death by 28 but not 90 days. Kaplan-Meier survival curves by time period of diagnosis are shown in Figure 1. Table 1. Multivariable Cox-Proportional Hazard Model for Mortality at 28 and 90-days Among Solid Organ Transplant Recipients Hospitalized for Covid-19 (N=979) Figure 1. Survival among SOT recipients hospitalized for Covid-19 by diagnosis time period Vertical tick marks represent censored cases. Early 2020 refers to cases diagnosed between March 1 and June 19, 2020 and late 2020 refers to cases diagnosed between June 20 and December 31, 2020. Conclusion Approximately 20% of deaths among SOTr hospitalized for Covid-19 occurred between days 29 and 90. Future investigations are required to discern the mechanism(s) for the improvement in early, but not late, mortality among SOTr with Covid-19 during the course of the pandemic. Disclosures Madeleine R. Heldman, MD, Cigna Lifesource (Other Financial or Material Support, Speaking honoraria)Thermo Fisher Scientific (Other Financial or Material Support, Speaking honoraria) Olivia S. Kates, MD, Merk (Scientific Research Study Investigator) Ajit P. Limaye, MD, astellas (Scientific Research Study Investigator)CTI (Scientific Research Study Investigator)GSK (Consultant)Johnson&Johnson (Other Financial or Material Support, Adjudication Committee)merck (Consultant, Grant/Research Support, Scientific Research Study Investigator)moderna (Scientific Research Study Investigator)Novartis (Other Financial or Material Support, DMC member)Novo Nordisk (Consultant)

scholarly journals 686. Elevations in TNFα and IL-18 are Associated with Increased Risk of Probable Cytomegalovirus Tissue Invasive Disease in Solid Organ Transplant Recipients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S396-S397
Author(s):  
Andrew H Karaba ◽  
Alexis Figueroa ◽  
Stuart C Ray ◽  
Robin K Avery ◽  
Robin K Avery ◽  
...  
Keyword(s):  
Viral Load ◽  
Research Study ◽  
Organ Transplant ◽  
Scientific Research ◽  
Principal Component ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Study Investigator ◽  
Cmv Disease ◽  
Cmv Dnaemia

Abstract Background Human cytomegalovirus (CMV) continues to cause significant morbidity and mortality in solid organ transplant (SOT) recipients despite prophylaxis. Tissue invasive CMV disease (TI-CMV) can lead to end-organ damage and graft loss. Diagnosing TI-CMV can be challenging as CMV viral load in the blood does not always correlate with episodes of TI-CMV and therefore definitive diagnosis often requires an invasive procedure such as bronchoscopy or colonoscopy. The purpose of this study was to determine if proinflammatory cytokines, including IL-18, are elevated in SOT recipients with probably TI-CMV as a way to identify patients at risk for this severe form of CMV disease. Methods The electronic medical record was searched for adult SOT recipients who were tested for CMV via blood qPCR during an 11-month period.Twenty-nine SOT recipients were identified that had episodes of CMV DNAemia without other concomitant infections during this time period. Patients were divided into those that had probable TI-CMV and those with CMV DNAemia alone, by chart review. Inflammatory cytokines (IFNγ, TNFα, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-18, and IL-1RA) were measured in residual plasma from these patients using a commercially available multiplex assay for at least two time points during the study period. Wilcoxon-Rank-Sum, logistic regression, and principal component analysis was performed comparing patients with and without probable TI-CMV. Results Patients with probable TI-CMV had significantly higher IL-18, TNFα, and IL-1β than patients with CMV DNAemia alone (p < 0.001, < 0.001, and < 0.05 respectively). When adjusting for transplant type and CMV recipient serostatus, elevations in TNFα (OR 1.43, 95% CI 1.07-1.92) and IL-18 (OR 2.00, 95% CI 1.06-3.75) were associated with increased odds of having probable TI-CMV. In principal component analysis the combination of CMV viral load, IL-18, TNFa, and IL-1β accounted for 80% of the variance in the data. Conclusion TNFα and IL-18 in combination with CMV viral load may be useful in predicting likelihood of TI-CMV. This is important in situations where tissue biopsies are not feasible, and adds to our diagnostic capability for TI-CMV in SOT recipients. Disclosures Stuart C. Ray, MD, miDiagnostics, Inc. (Board Member, Research Grant or Support) Robin K. Avery, MD, Aicuris (Scientific Research Study Investigator)Astellas (Scientific Research Study Investigator)Chimerix (Scientific Research Study Investigator)Merck (Grant/Research Support, Scientific Research Study Investigator)Oxford Immunotec (Scientific Research Study Investigator)Qiagen (Scientific Research Study Investigator)Takeda/Shire (Scientific Research Study Investigator)

scholarly journals 673. Updated CLSI Ciprofloxacin Breakpoints from a Multicenter Assessment for Enterobacterales, Salmonella spp. and Pseudomonas aeruginosa Using MicroScan Dried Gram Negative MIC Panels

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S391-S391
Author(s):  
Maria M Traczewski ◽  
Denise Beasley ◽  
Amanda Harrington ◽  
Sharon DesJarlais ◽  
Omai Garner ◽  
...  
Keyword(s):  
Research Study ◽  
Scientific Research ◽  
Reference Panel ◽  
Broth Microdilution ◽  
Salmonella Spp ◽  
Research Personnel ◽  
Gram Negative ◽  
Material Support ◽  
Study Investigator ◽  
Support Research

Abstract Background Updated US FDA/CLSI ciprofloxacin breakpoints were evaluated against data from a multicenter clinical study with Enterobacterales, Salmonella spp. and P. aeruginosa on a MicroScan Dried Gram-negative MIC (MSDGN) Panel. MIC results were compared to results obtained with frozen broth microdilution panels prepared according to CLSI methodology. Methods MSDGN panels were evaluated at three clinical sites by comparing MIC values obtained using the MSDGN panels to MICs utilizing a CLSI broth microdilution reference panel. Data from the combined phases of efficacy and challenge included 803 Enterobacterales, Salmonella spp. and P. aeruginosa clinical isolates tested using the turbidity and Prompt® methods of inoculation. To demonstrate reproducibility, a subset of 12 organisms were tested on MSDGN panels at each site during reproducibility. MSDGN panels were incubated at 35 ± 1ºC and read on the WalkAway System, the autoSCAN-4 instrument, and visually. Read times for the MSDGN panels were at 16-20 hours. Frozen reference panels were prepared and read according to CLSI methodology. FDA and CLSI breakpoints (µg/mL) used for interpretation of MIC results were: Enterobacterales ≤ 0.25 S, 0.5 I, ≥ 1 R; Salmonella spp. ≤ 0.06 S, 0.12-0.5 I, ≥ 1 R; P. aeruginosa ≤ 0.5 S, 1 I, ≥ 2 R. Results Essential and categorical agreement was calculated compared to frozen reference panel results. Results for isolates tested during efficacy and challenge with Prompt inoculation and manual read are as follows: Conclusion Ciprofloxacin MIC results for Enterobacterales, Salmonella spp., and P. aeruginosa obtained with the MSDGN panel correlate well with MICs obtained using frozen reference panels using updated FDA/CLSI interpretive criteria in this multicenter study. * PROMPT® is a registered trademark of 3M Company, St. Paul, MN USA. BEC, the stylized logo and the BEC product and service marks mentioned herein are trademarks or registered trademarks of Beckman Coulter, Inc. in the US and other countries. Disclosures Maria M. Traczewski, BS MT (ASCP), Beckman Coulter (Scientific Research Study Investigator) Denise Beasley, BS, Beckman Coulter (Other Financial or Material Support, Research personnel) Amanda Harrington, PhD, Beckman Coulter (Scientific Research Study Investigator) Sharon DesJarlais, BS, Beckman Coulter (Other Financial or Material Support, Research personnel) Omai Garner, PhD, D(ABMM), Beckman Coulter (Scientific Research Study Investigator) Christine Hastey, PhD, Beckman Coulter (Employee) Regina Brookman, BS, Beckman Coulter (Employee) Zabrina Lockett, MS, Beckman Coulter (Employee) Jennifer Chau, PhD, Beckman Coulter (Employee)

Immunization of Solid Organ Transplant Candidates and Recipients

2018 ◽  
Vol 32 (3) ◽  
pp. 517-533 ◽  
Author(s):  
Christian Donato-Santana ◽  
Nicole M. Theodoropoulos
Keyword(s):  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Candidates

scholarly journals Exercise for Solid Organ Transplant Candidates and Recipients

2019 ◽  
Vol 103 (9) ◽  
pp. e220-e238 ◽  
Author(s):  
Tania Janaudis-Ferreira ◽  
Sunita Mathur ◽  
Robin Deliva ◽  
Nancy Howes ◽  
Catherine Patterson ◽  
...  
Keyword(s):  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Candidates

scholarly journals 568. Comparison of Humoral Immune Response to the SARS-CoV-2 BNT162b2 Vaccine Between Solid Organ Transplant Recipients and Healthy Controls

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S386-S386
Author(s):  
Ahmad Yanis ◽  
Zaid Haddadin ◽  
Andrew Speaker ◽  
Danya Waqfi ◽  
Rana Talj ◽  
...  
Keyword(s):  
Organ Transplant ◽  
Vaccine Dose ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Healthy Controls ◽  
Transplant Recipients ◽  
Research Support ◽  
Material Support ◽  
Organ Transplant Recipients ◽  
Solid Organ Transplant Recipients

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased morbidity and mortality in immunocompromised individuals, including solid organ transplant recipients (SOTR). Despite being excluded from phase 1-3 SARS-CoV-2 vaccine clinical trials, SOTR were identified as high-risk populations and prioritized for vaccination in public health guidelines. We aimed to evaluate the antibody response to two doses of the BNT162b2 (Pfizer-BioNTech) vaccine in SOTR as compared to healthy controls (HC). Methods SOTR and HC scheduled to receive two doses of BNT162b2 vaccine and able to complete required follow-up visits were enrolled. Blood specimens were collected from participants before receiving the first and second doses and 21-42 days after the second dose. Enzyme-linked immunosorbent assay (ELISA) was used to detect immunoglobulin G (IgG) to the SARS-CoV-2 spike receptor-binding domain (RBD). Generalized estimating equations with a working independence correlation structure were used to compare anti-RBD IgG levels between SOTR and HC at each study visit and within each group over time. All models were adjusted for age, sex, and pre-vaccination seroreactivity in the ELISA. Results A total of 54 SOTR and 26 HC were enrolled, with mean (SD) ages of 72 (3.6) and 62 (6.7) years, 61% and 35% were male, and 91% and 88% were white, respectively. The most common organ transplant types were kidney (41%) and liver (37%). All SOTR were receiving calcineurin inhibitors. The median time post-transplantation was 7 years. SOTR had markedly lower mean anti-RBD IgG levels when compared to HC with adjusted mean differences of -0.76 (95%CI: [-1.04, -0.47]; p < 0.001) ELISA units (EU) and -1.35 (95%CI [-1.68, -1.01]; p < 0.001) EU after the first and second doses, respectively (Figure 1). Both groups had a significant increase in anti-SARS-CoV-2 IgG levels after the second dose. However, the magnitude was lower in SOTR, 0.49 (95%CI [0.31, 0.69]; p < 0.001) EU than in HCs, 1.08 (95% CI [0.91, 1.24]; p < 0.001) EU. Figure 1. Anti-SARS-CoV-2 RBD IgG levels in solid organ transplant recipients and healthy controls before receiving the BNT162b2 vaccine (baseline), post-vaccine dose 1, and post-vaccine dose 2. Conclusion Our study showed SOTR mounted weaker humoral immune responses than HC to SARS-CoV-2 vaccines. Given a lower response, SOTR should continue to practice social distancing and masking until data on vaccine efficacy are available in this vulnerable population. Disclosures Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it's a education grant, supported by genetech)Quidel (Grant/Research Support, Other Financial or Material Support, Donation of supplies/kits)Sanofi (Grant/Research Support, Other Financial or Material Support, HAI/NAI testing) Natasha B. Halasa, MD, MPH, Genentech (Individual(s) Involved: Self): I receive an honorarium for lectures - it's a education grant, supported by genetech, Other Financial or Material Support, Other Financial or Material Support; Sanofi (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support

scholarly journals LB1. Remdesivir for the Treatment of High-Risk Non-Hospitalized Individuals With COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S806-S807
Author(s):  
Joshua A Hill ◽  
Roger Paredes ◽  
Carlos Vaca ◽  
Jorge Mera ◽  
Brandon J Webb ◽  
...  
Keyword(s):  
High Risk ◽  
Research Study ◽  
Scientific Research ◽  
Panel Member ◽  
Research Support ◽  
Review Panel ◽  
Double Blind ◽  
Material Support ◽  
Double Blind Placebo ◽  
Study Investigator

Abstract Background Remdesivir (RDV) is a potent nucleotide prodrug inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase that has demonstrated efficacy in the treatment of patients hospitalized with moderate to severe COVID-19. This Phase 3 (GS-US-540–9012) double-blind, placebo-controlled study compared the efficacy and safety of 3 days of RDV to standard of care in non-hospitalized, high-risk participants with confirmed COVID-19. Table 1. COVID-19 related hospitalization or death, COVID-19 related medically attended visits or death, and Treatment Emergent Adverse Events Methods Participants were randomly assigned 1:1 to receive intravenous (IV) RDV (200 mg on day 1, 100 mg on days 2 to 3) or placebo. The primary efficacy endpoint was composite COVID-19 hospitalization or all-cause death by day 28 and compared using Cox proportional hazards model with baseline stratification factors as covariates. The primary safety endpoint was proportion of participants with treatment-emergent adverse events. Study enrollment was terminated early for administrative reasons in light of the evolving pandemic. Results 562 patients underwent randomization and started their assigned treatment (279, RDV; 283, placebo). Baseline demographics and characteristics were balanced across arms. Overall, 52% were male, 44% were Hispanic/Latino ethnicity and 30% were ≥ 60 years old. The most common comorbidities were diabetes mellitus (62%), obesity (56%; median BMI, 30.7), and hypertension (48%). Median baseline SARS-CoV-2 RNA nasopharyngeal viral load was 6.2 log10 copies/mL. Treatment with RDV significantly reduced COVID-19 hospitalization or all-cause death by day 28 (HR, 0.13; 95% CI, 0.03 – 0.59; p = 0.008; Table 1) compared to placebo. Participants receiving RDV also had significantly lower risk for COVID-19-related medically attended visits or all-cause death by day 28 compared to placebo (HR, 0.19; 95% CI, 0.07 – 0.56; p = 0.002; Table 1). No deaths occurred in either arm by day 28. There was no difference between arms in time-weighted average change in nasopharyngeal viral loads from baseline up to day 7. The proportion of patients with AEs was similar between arms (Table 1); the most common AEs in the RDV arm were nausea (11%), headache (6%), and diarrhea (4%). Conclusion A 3-day course of IV RDV was safe, well tolerated and highly effective at preventing COVID-19 related hospitalization or death in high-risk non-hospitalized COVID-19 patients. Disclosures Joshua A. Hill, MD, Allogene (Individual(s) Involved: Self): Consultant; Allovir (Individual(s) Involved: Self): Consultant, Grant/Research Support; Amplyx (Individual(s) Involved: Self): Consultant; Covance/CSL (Individual(s) Involved: Self): Consultant; CRISPR (Individual(s) Involved: Self): Consultant; Gilead (Individual(s) Involved: Self): Consultant, Grant/Research Support; Karius: Grant/Research Support, Scientific Research Study Investigator; Medscape (Individual(s) Involved: Self): Consultant; Octapharma (Individual(s) Involved: Self): Consultant; OptumHealth (Individual(s) Involved: Self): Consultant; Takeda (Individual(s) Involved: Self): Consultant, Grant/Research Support, Scientific Research Study Investigator Roger Paredes, MD, PhD, Gilead Sciences, Inc (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member) Carlos Vaca, MD, Gilead Sciences, Inc (Scientific Research Study Investigator) Jorge Mera, MD, Gilead Sciences, Inc (Consultant, Study Investigator (payment to employer not self)) Gilberto Perez, MD, Gilead Sciences, Inc (Scientific Research Study Investigator) Godson Oguchi, MD, Gilead Sciences, Inc (Scientific Research Study Investigator) Pablo Ryan, MD PhD, Gilead Sciences, Inc (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member) Jan Gerstoft, MD, Gilead Sciences, Inc (Other Financial or Material Support, Study Investigator (payment to employer)) Michael Brown, FRCP PhD, Gilead Sciences, Inc (Scientific Research Study Investigator, Investigator for numerous remdesivir trials (employer received compensation)) Morgan Katz, MD, MHS, Roche (Individual(s) Involved: Self): Advisor or Review Panel member; Skinclique (Individual(s) Involved: Self): Consultant Gregory Camus, PhD, Gilead Sciences (Employee, Shareholder) Danielle P. Porter, PhD, Gilead Sciences (Employee, Shareholder) Robert H. Hyland, DPhil, Gilead Sciences, Inc (Shareholder, Other Financial or Material Support, Employee during the conduct of this trial) Shuguang Chen, PhD, Gilead Sciences, Inc (Employee, Shareholder) Kavita Juneja, MD, Gilead Sciences, Inc (Employee) Anu Osinusi, MD, Gilead Sciences, Inc (Employee, Shareholder) Frank Duff, MD, Gilead Sciences, Inc (Employee, Shareholder) Robert L. Gottlieb, MD, Eli Lilly (Scientific Research Study Investigator, Advisor or Review Panel member)Gilead Sciences (Scientific Research Study Investigator, Advisor or Review Panel member, Other Financial or Material Support, Gift in kind to Baylor Scott and White Research Institute for NCT03383419)GSK (Advisor or Review Panel member)Johnson and Johnson (Scientific Research Study Investigator)Kinevant (Scientific Research Study Investigator)Roche/Genentech (Scientific Research Study Investigator)

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