Organ Failure Research Articles

P-749. Prognostic Determinants in Patients with Necrotizing Fasciitis in a Referral Hospital in Nicaragua

Abstract Background Necrotizing fasciitis is a serious condition in which timely diagnosis and therapeutic approaches, both medical and surgical, play an essential role in prognosis. In Nicaragua, the prognostic determinants for this clinical condition in different hospital institutions have not been formally evaluated. The aim of this study was to establish factors that could be determinant for the prognosis of patients with necrotizing fasciitis in a national referral hospital.Table 1.Organ Failure at the Admission in Patients with Necrotizing Fasciitis Methods This is a retrospective, cross-sectional, analytical study. It was conducted with patients over 15 years of age with a diagnosis of necrotizing fasciitis hospitalized between January 201 and December 2023 in Dr. Fernando Vélez Paiz Hospital in Managua, Nicaragua. Clinical factors such as comorbidities or organ failure on admission, as well as the LRINEC score, and the times of administration of the first dose of antibiotic and surgical intervention were analyzed and correlated with the clinical outcome of the patients.Table 2.Potentials Prognosis Determinants in Necrotizing Fasciitis that were Evaluated Results A total of 45 patients were included in the study, 60% of whom were women. The mean age was 56.0 ± 14.6 years-old. 86.7% of patients had at least one comorbidity. At the time of diagnosis, 31.1% of patients had renal insufficiency, 24.4% had shock, and 15.6% had altered state of consciousness (Table 1). 25 patients died for a mortality rate of 44.4%. The mean time from suspected diagnosis and administration of the first dose of antibiotics was 2.5 ± 1.4 hours (Table 2). Only 20% of patients received the first dose of the antibiotic at the first hour. 17.8% of patients underwent surgery within 6 hours of diagnosis. There was no association between prognosis and the time of initiation of antibiotic therapy and the time of initiation of surgical treatment after diagnosis of necrotizing fasciitis, probably due to a problem of sample size. 60% of the deceased had LRINEC ≥ 8 points, while only 28% in the group of survivors, OR(95%CI): 3.85 (1.10-13.46) (Table 3).Table 3.LRINEC and Mortality in Patients with Necrotizing Fasciitis Conclusion Patients with necrotizing fasciitis mostly have comorbidity, mainly diabetes, and almost a quarter of them have shock and a third have renal failure. A LRINEC score greater than or equal to 8 points significantly increases the risk of death in this type of patient. Disclosures All Authors: No reported disclosures

Whole blood exchange ameliorates acute hemolytic anemia by reducing inflammation and oxidative stress in rats.

Hemolytic anemia (HA) is characterized by massive destruction of red blood cells (RBCs) and insufficient oxygen supply, which can lead to shock, organ failure, even death. Recent studies have preliminarily demonstrated the therapeutic effectiveness of whole blood exchange (WBE) in the management of acute hemolytic anemia and exhibited potential for reducing the duration of corticosteroid treatment, while the underlying mechanism of WBE therapy was not investigated in preclinical study. Hence, we investigate the therapeutic mechanisms of WBE in HA through established continued WBE therapy in rats creatively. This study aims to examine the mechanism of WBE on phenylhydrazine hydrochloride-induced hemolytic anemia in SD rats to aid the development of therapeutics for drug-induced hemolytic anemia (DIHA). Research results demonstrated the efficacy of WBE therapy in reducing mortality and ameliorating anemia in DIHA, as evidenced by significant improvements in representative hematological parameters such as RBCs, hemoglobin, and lactate dehydrogenase levels. Additionally, WBE indicated the ability to suppress oxidative stress and inflammation, and it mitigated organ damage and biochemical function by stabilizing hepatic ferroportin levels and decreasing organ iron content. These results highlighted the effectiveness of WBE as an innovative treatment for HA, furnishing evidence to prioritize it over traditional blood transfusion for severe anemias.

P-187. Clinical Profile of Atypical Manifestations of Dengue Fever and Severe dengue fever in children in Argentina

Abstract Background The clinical presentation of dengue fever has a wide spectrum; unussual manifestations have been reported and with the rising disease burden, atypical manifestations are also on rise, but are underreported and often missed due to the lack of awareness among health care professionals. In Argentina we are witnessing the largest historical outbreak of dengue in 2024. The objective of the study is to study the clinical profile and outcome of atypical and severe manifestations of dengue fever in children. Methods All children (0–18 y of age) confirmed as dengue fever at a tertiary care hospital at Buenos Aires, Argentina between January 2023-April 2024 were reviewed retrospectively from hospital case records. The diagnosis was confirmed by NS1 antigen/IgM based ELISA or inmunocromatography test, PCR. The data was analyzed using EpiInfo 7.2 Results Out of 213 children admitted with dengue fever, 7 % had severe dengue. Atypical manifestations were seen in 37 cases ( 17 %). Mean age of presentation was 6.5 (5.2) y. M: F ratio was 1.1:1. The common manifestations of severe dengue infection were shock (80 %), bleeding (20 %) and multi organ dysfunction (6 %). The most common atypical manifestations of dengue fever were hepatitis (19%), seizures (8 %), acalculous cholecystitis (8%), myositis (8%),pneumonia (8%), febrile infant without focus (8%), febrile diarrhea (19 %). The other atypical manifestations present were ataxia, meningitis, acute respiratory distress syndrome (ARDS), myocarditis, lymphadenitis, prolonged fever, pericardial and pleural effusion. There was one death (0.4 %). Conclusion The atypical manifestations of dengue fever are no more a rare entity. Clinicians should have a high index of suspicion and surveillance for atypical manifestations of dengue fever as lack of timely detection and management could be fatal. Disclosures All Authors: No reported disclosures

P-1236. Vancomycin Population Pharmacokinetics Using Volumetric Absorptive Microsampling in Critically Ill Children with Multiple Organ Dysfunction Syndrome

Abstract Background Vancomycin (VAN) is the most frequently used antibiotic for hospitalized patients in the United States. Wide use occurs as it is a first line treatment for severe gram-positive bacterial infections in both adults and pediatrics. Most VAN dosing in children with multiple organ dysfunction syndrome (MODS) is guided via population pharmacokinetic (PK) approaches based on creatinine clearance equations and frequent samplings. Volumetric absorptive microsampling (VAMS) offers sampling procedures that require as little as 20 mcL of blood. The primary objective of this study was to develop a population PK (popPK) model for VAN in children with MODS using VAMS.Table 1.Population parameter estimation values. Methods We conducted a multi-center prospective observational study of VAN PK in pediatric MODS. Subjects (< 18 years) participating in a larger observational study of children with MODS in the ICU were eligible. Up to 15 PK samples were collected over 3 consecutive days, along with pertinent covariate data. Parametric popPK modeling was performed using Monolix 2024R1. Covariate selection was based on improvements in objective function value and physiologic relevance. Children on CRRT were excluded from the present analyses. Subjects in our interim analysis were also excluded from analysis if they were missing demographic information or were pending data queries on VAN concentrations.Figure 1.Individual weighted residuals according to time and individual predictions. Results 52 subjects from 8 sites were included with a median age of 6.5 y (range: 2 m–17 y) and a median weight of 24.5 kg (range: 3-214). A two-compartment model with clearance adjusted for allometric scaling and estimated glomerular function best described the data. Population predictions were modest (R2=0.28) whereas individualized predictions were improved (R2=0.61). Between subject variation for clearance and volume of distribution was high even after correcting for U25 creatinine clearance (92.7% and 107.9%, CV% respectively).Figure 2.Observed vs. population (A) and individual (B) predictions for the model. Conclusion Children with MODS display high between subject variability of VAN clearance and volume of distribution. Frequent sampling is needed because “stead-state” does not exist in the early period of MODS for children. VAMS can facilitate small volume sampling and future Bayesian models based on data such as these can facilitate fewer sampling events to classify the patient’s dynamic clearance. Disclosures Nathaniel J. Rhodes, PharmD MS, Apothecademy, LLC: Advisor/Consultant Kevin J. Downes, MD, Paratek, Inc.: Grant/Research Support|Veloxis Pharmaceuticals, Inc.: Grant/Research Support Marc H. Scheetz, PharmD, MSc, Abbvie: Advisor/Consultant|Basilea: Advisor/Consultant|Cidara: Advisor/Consultant|DoseMe: Advisor/Consultant|Entasis: Advisor/Consultant|F2G: Advisor/Consultant|GSK: Advisor/Consultant|Lykos: Advisor/Consultant|Roche: Advisor/Consultant|Third Pole Therapeutics: Advisor/Consultant|Xelia: Advisor/Consultant

Health Care Resource Use and Costs After Hospitalization With Multiple Organ Dysfunction in Children.

Multiple organ dysfunction (MOD) is a leading cause of in-hospital child mortality. For survivors, posthospitalization health care resource use and costs are unknown. To evaluate longitudinal health care resource use and costs after hospitalization with MOD in infants (aged <1 year) and children (aged 1-18 years). This retrospective cohort study used nationwide data from 2004 to 2019 from Optum's deidentified Clinformatics Data Mart Database, an insurance claims database. Infants and children from birth to age 18 years with an index hospitalization between January 1, 2005, and December 31, 2018, were included. Infants (age <1 year) and children (age 1-18 years) with MOD (MOD cohort) or without MOD (non-MOD cohort) were separately identified, and cohorts were propensity score weighted to balance demographics and pre-index hospitalization characteristics, including health care use and comorbidities. The data were analyzed between January 7, 2022, and September 8, 2023. Weighted generalized estimating equations were used to evaluate differences between cohorts in rehospitalizations, emergency department visits, and health care costs up to 5 years after the index hospitalization. During the study period, 9671 children in the MOD cohort were compared with 1 691 793 children in the non-MOD cohort in the weighted sample. Infants comprised 67.4% of the MOD cohort (mean [SD] age at index hospitalization, 0.1 [0.8] years; 51.2% male) and 87% of the non-MOD cohort (mean [SD] age at index hospitalization, 0.1 [0.8] years; 50.8% male), and children comprised 32.5% of the MOD cohort (mean [SD] age at index hospitalization, 11.6 [5.7] years; 50.7% female) and 13.0% of the non-MOD cohort (mean [SD] age at index hospitalization, 11.5 [5.5] years; 51.3% female). The infant MOD cohort had more emergency department visits, with an adjusted incidence rate ratio of 1.76 (95% CI, 1.56-1.97) at 30 days; this difference persisted for years 1 through 5. Children had a similar pattern except at 30 days among those who acquired new organ-supportive technology during the index hospitalization. Among infants, the MOD cohort had more rehospitalizations, with an adjusted incidence rate ratio of 12.45 (95% CI, 11.40-13.59) at 30 days; this difference persisted for years 1 through 5. A similar pattern was observed among children. Annual health care costs were higher for the MOD cohort in year 1 (infants: mean [SD], $80 133 [$6543] vs $5183 [$19] [P < .001]; children: mean [SD], $54 113 [$17 544] vs $10 935 [$95] [P < .001]) and in all years through year 5. In this cohort study of nearly 1.7 million children, survivors of MOD accrued substantial ongoing health care resource use and cost burden after the index hospitalization. These findings suggest that follow-up care of survivors of MOD should include economic well-being alongside measures of clinical health.

P-2263. Are you PRePared After Transplant?

Abstract Background Solid organ transplantation (SOT) is a life-saving medical procedure that can improve the quality of life of individuals with end-stage organ failure. Given the scarcity of organs, it is important to safeguard those implanted and prevent infections. Transplant Infectious Disease physicians help mitigate infectious risk both before and after surgery. One important preventable infection is Human Immunodeficiency Virus (HIV). Pre-exposure prophylaxis (PrEP) is effective in reducing the risk of HIV infection. Yet no study has examined PrEP use in SOT patients. The CDC reports that 30% of patients that may benefit from PrEP are prescribed them in the US. No similar statistic exists for SOT patients. Figure 1 Demographics for SOT patients with possible exposure to HIV. Purple represents those without PrEP. Green represents those with PrEP. Methods To obtain quantitative support for further study, a large, multi-center database (Trinetx) was queried. Trinetx contains deidentified data from hundreds of international healthcare organizations (HCOs) dating back about seven years. The retrospective query included 68 HCOs with patients that met the following search inclusion criteria (based on ICD codes): SOT patient without the diagnosis of HIV, prescribed PrEP, and possible exposure risk for HIV. Results 147,145 SOT patients were identified that did not carry the diagnosis of HIV. Only 160 patients (0.11%) were prescribed PrEP, identified as the following three regimens: tenofovir alafenamide + emtricitabine, tenofovir disoproxil + emtricitabine, or cabotegravir. To risk-stratify HIV exposure, the original cohort of 147,475 SOT patients without HIV were analyzed with ICD codes for HIV exposure. This search identified 2,565 patients coded for HIV exposure. Given that only 160 patients were prescribed PrEP in the cohort, 2,405 patients may have benefited from PrEP but were not prescribed these medications. Patients on PrEP after SOT were predominantly male (78%) and White/Caucasian (58%). Identifying as Asian was a significant factor in using PrEP after SOT (p&amp;lt; 0.0001). Female gender was a significant demographic not utilizing PrEP despite possible exposure to HIV (p&amp;lt; 0.0001). (Figure 1). Conclusion This large database study shows that PrEP is underutilized in SOT patients. Further study—including surveys of sexual practices, provider knowledge, and attitudes towards PrEP, as well as single-center analysis—is needed. Disclosures All Authors: No reported disclosures

Acute Kidney Injury in Critically Ill Children: Prevalence, Progression, Recovery Mortality, and Impact of Severity

Introduction: Acute kidney injury (AKI) among the pediatric population is considered a risk factor for mortality and morbidities during pediatric intensive care unit (PICU) admission. The association between AKI and increased mortality risk and length of stay (LOS) is still inconclusive. This retrospective cohort study aimed to evaluate the impact of AKI severity upon critical management and clinical parameters with an evaluation of severity progression among AKI patients admitted to the PICU at a tertiary care hospital. Methods: AKI, defined with the Kidney Disease Improving Global Outcomes (KDIGO) classification, was determined based on serum creatinine and urine output with respect to the patient’s baseline value. The following outcomes were examined: mortality, mechanical ventilation use, use of non-invasive ventilation, recovery at discharge, and LOS in the hospital and PICU stratified by type of AKI upon admission. Medical records of the 165 included patients were reviewed for clinical data and study outcomes. Results: The median age of the patients was 7 years (IQR 1.5–10 years), and 58% were boys; 78 (47.2%) had stage 1 AKI, 49 (29.71%) had stage 2 AKI, and 38 (23%) had stage 3 AKI at admission. The mortality rate was 26%. The median LOS in the PICU was statistically significant between AKI stages, with a higher median LOS among patients with AKI stage 3 at admission. Using the maximum KDIGO stage, there was no association between AKI and mortality (adjusted OR 1.91, 95% CI 0.05), whereas for the mechanical ventilation outcome, the adjusted OR was 1.84 (95% CI 0.42–8.1). Conclusions: The severity of AKI is not associated solely with mortality and clinical outcomes as the numbers of comorbidities and organ failures contribute to mortality. However, improving awareness of AKI and understanding the disease progression course would reduce acute and long-term morbidity and mortality.

Urinary electrolyte parameters in sepsis-associated acute kidney injury: A prospective observational study

Background and Aims: Sepsis-associated acute kidney injury (SA-AKI) significantly contributes to morbidity and mortality. Current biomarkers have limitations, necessitating the exploration of alternative indicators. This study aims to evaluate various urinary electrolyte parameters to predict SA-AKI. Methods: A prospective observational study included 111 sepsis patients within 24 h of admission. Urinary electrolyte samples were collected, and indices were calculated. Patients were monitored for 7 days to assess for acute kidney injury (AKI) according to Kidney Disease Improving Global Outcomes (KDIGO) definition criteria, mortality rates, and the need for renal replacement therapy. Mann-Whitney U test and Chi-squared test were used to analyse continuous and categorical variables, respectively. Receiver-operating characteristic (ROC) curves were constructed to determine to discriminatory ability of various parameters in predicting AKI. Results: Of 111 patients, 42.3% developed AKI, with a mortality rate of 59.5%. When evaluating urinary parameters, the product of urine sodium and urine creatinine exhibited the maximum full form [area under the receiver operating characteristic (AUROC): 0.66; 95%CI: 0.56, 0.77)], and the parameter of fractional excretion of potassium (FeK) exhibited an AUROC of 0.62 (95%CI: 0.51, 0.72). Furthermore, 2-hour excretion of potassium revealed a statistically significant correlation with 2-hour creatinine clearance (r = 0.62, P &lt; 0.001). Logistic regression models, incorporating Sequential Organ Failure Assessment (SOFA) score, FeK, and urine sodium concentration as variables (P = 0.020, 0.044, and 0.033, respectively), achieved an AUROC of 0.751 in predicting AKI. Conclusion: Urine sodium levels and fractional potassium excretion moderately effectively predict AKI in sepsis patients. Urine potassium excretion correlates with glomerular filtration rate.

NEUROVASCULAR DYSREGULATION IN PREECLAMPSIA- PATHOPHYSIOLOGY AND CLINICAL IMPLICATIONS

After 20 weeks of pregnancy, proteinuria and new-onset hypertension are hallmarks of preeclampsia, a complex hypertensive pregnancy disease that frequently coexists with systemic organ failure. It continues to be a major cause of maternal and newborn morbidity and mortality, affecting 5–8% of pregnancies worldwide, especially in environments with low resources. Although it has historically been associated with placental malfunction, mounting data indicates a substantial neurovascular involvement, including disruption of the blood-brain barrier (BBB), neuroinflammation, and oxidative stress, which results in cerebral edema, ischemia, and bleeding. Headaches, seizures, visual abnormalities, and posterior reversible encephalopathy syndrome (PRES) are examples of neurological symptoms. The characteristics of preeclampsia, a complicated hypertensive pregnancy syndrome that often coexists with systemic organ failure, are proteinuria and new-onset hypertension after 20 weeks of pregnancy. It still accounts for 5–8% of pregnancies globally, particularly in low-resource settings, and is a leading cause of maternal and neonatal morbidity and mortality. Growing evidence suggests a significant neurovascular involvement, including disruption of the BBB, neuroinflammation, and oxidative stress, which leads to cerebral edema, ischemia, and bleeding, despite its historical association with placental dysfunction. Neurological symptoms include visual problems, headaches, seizures, and PRES. Long-term monitoring, supportive care, and neuroprotective techniques are crucial, especially for cardiovascular risks and postpartum problems. The burden of preeclampsia can be lessened by addressing health inequities and including preventive care. Its neurovascular and systemic interactions warrant more investigation in order to develop novel therapeutic strategies that will eventually enhance the results for mothers and newborns. KEYWORDS: Neurovascular dysregulation, preeclampsia, brain-blood barrier, Angiogenic dysregulation, Oxidative stress.

P-1868. Incidence of Rhabdomyolysis in Patients Receiving Daptomycin in a Community Hospital OPAT Program

Abstract Background Daptomycin is a favorable medication for outpatient parenteral antimicrobial therapy (OPAT) due to its low rate of serious adverse events, however one potential therapy complication is the development of rhabdomyolysis. The aim of this study was to determine the incidence of rhabdomyolysis within a community hospital’s OPAT program. Methods A retrospective chart review was performed of patients enrolled in the OPAT program and who received daptomycin therapy from December 2022 to August 2023. The primary outcome of the study was the percentage of patients who developed rhabdomyolysis while on daptomycin therapy. Secondary outcomes included the determination of any patient- or drug-specific risk factors that may have increased the risk of rhabdomyolysis. Patients were included if they were discharged on daptomycin and followed by the formal OPAT program during the study period. Patients who were less than 18 years of age or pregnant were excluded. Results There were 83 patients who received daptomycin during the study period and 5/83 (6%) developed rhabdomyolysis. There were 8 (9.6%) patients who had an elevated creatinine kinase (CK) but did not have further progression to rhabdomyolysis. The median daptomycin dose given to patients was 8 mg/kg. Four out of the five patients with rhabdomyolysis were female (80%). The mean BMI of those who developed rhabdomyolysis was 37.9. The mean onset of rhabdomyolysis was 10.8 days. No patients with rhabdomyolysis were on a concomitant statin. None of the five patients experienced death or permanent organ failure. Conclusion The development of rhabdomyolysis in our study was higher than anticipated based on previous phase 3 studies. This difference may be due to higher dosing used between studies. Potential factors to consider for increased risk of rhabdomyolysis based on this study include female gender and BMI greater than 35. Statin use did not appear to be associated with an increased risk of rhabdomyolysis. Daptomycin is still a safe and effective antibiotic in the OPAT setting, however CK should be closely monitored. Disclosures All Authors: No reported disclosures

P-2283. Reversing Antimicrobial Resistance (AMR) in Febrile Neutropenia. Is it Possible?

Abstract Background Multi-drug resistance in gram-negative bacilli is major cause of concern in managing patients with febrile neutropenia particularly among hematology-oncology patients. Reversing AMR has never been demonstrated previously in this setting. Table of various parameters comparing Cohort A and B Methods This retrospective study compares clinical and microbiological outcomes of patients admitted to hematology-oncology unit of a tertiary care center in India with febrile neutropenia and gram-negative bacteremia. Patients admitted from April 2019- April 2020 were included in Cohort A and April 2023-April 2024 were included in Cohort B. Bar diagram showing change in resistance pattern in two cohorts Results A total of 212 patients (Cohort A: 114, Cohort B 98) were included in this study (Table 1). Mean age (53 ± 21.2 years vs 46.5 ± 17.5; p = 0.417) and gender distribution (females: 40.3% vs 36.7%; p = 0.58) were comparable and so was distribution of malignancies. Mean Sequential Organ Failure Assessment Score (6 ± 2.29 vs 5 ±3.50; p = 0.245), mean Charlson co-morbidity Index (3 ± 2.4 vs 3 ± 2.1; p = 0.65), mean Pitts Bacteremia score (1 ± 1.46 vs 1 ± 1.58; p = 0.334) and 30 day crude mortality (28.7% vs 28.6%; p = 0.935) were not statistically significant between the two cohorts. Incidence (Figure 1)of carbapenem resistance (CR) Klebsiella pneumoniae (56 (90.3%) vs 16 (47.1%); p &amp;lt; 0.01), CR E. coli (14 (43.7%) vs 6 (23.1%); p = 0.099) and DTR (difficult-to-treat) Pseudomonas aeruginosa (10 (83.3%) vs 2 (10.0%); p &amp;lt; 0.01) significantly reduced in Cohort B as compared to Cohort A. Involvement of Infectious Disease (ID) service, following antibiotic stewardship (AMS) team advice, improved diagnostic facility and infection control were major interventions during the study period. Conclusion This study highlights that incorporating ID service and following AMS activities along with other infrastructure development can reverse AMR in high risk setting like febrile neutropenia among hematology-oncology patients. Disclosures All Authors: No reported disclosures

P-913. Etiologies, Clinical Characteristics and Prognostic impact of Increased Intracranial Pressure in Adults with Encephalitis

Abstract Background Encephalitis involves symptoms like reduced consciousness and seizures, diagnosed via lumbar puncture and brain imaging. Increased intracranial pressure (ICP) and its effect is well described in meningitis/ventriculitis and serve as poor prognostic factors. Data on ICP in encephalitis is limited, highlighting the need for further research.Table 1.Demographic, Clinical Characteristics, and Initial Presentations of 647 Adults with Encephalitis by Opening Pressure Measurement Status and DegreeAbbreviations: APACHE, Acute Physiology and Chronic Health Evaluation; GCS, Glasgow Coma Scale; MAP, Mean Arterial Pressure; qSOFA, Quick Sequential Organ Failure Assessment. Methods Retrospective study at University of Texas and Johns Hopkins, 2002-2023, on 647 patients over 17 years old with encephalitis. Data analyzed via SPSS software.Table 2.Laboratory Findings, Etiology, and Imaging Results in Encephalitis Patients by Opening Pressure Measurement Status and DegreeAbbreviations: CSF, cerebral spinal fluid; CT, computed tomography; EEG, electroencephalogram; HSV, herpes simplex virus; MRI, magnetic resonance imaging; PMN, polymorphonuclear leukocyte; RBC, red blood cell; VZV, varicella zoster virus; WBC, white blood cell. Results Our study had 647 patients, with ICP measured in 298 (46%). Patients were categorized by ICP levels: &amp;lt; 30mmHg (242) and ≥30mmHg (56). Demographics such as gender, race, and age showed no variance across ICP. Comorbidity profiles were similar, though immunocompromised patients more frequently had ICP measurement (p=0.010). Symptoms like photophobia were uniformly distributed, but seizures and fever were more common in those measured for ICP (p=0.007 &amp; p=0.013). Nuchal rigidity was higher in those with ICP ≥30mmHg (31% vs. 15%, p=0.031). Blood and cerebrospinal fluid analyses did not differ across groups. The leading etiologies identified were viral (32.9%) and autoimmune (18.1%), with no cause specifically linked to elevated ICP. Neuroimaging was more likely to be abnormal in patients with ICP measured (65% vs. 53%, p=0.004). Those with abnormal EEGs were more likely to have ICP measured (82% vs. 74%, p=0.050), but abnormal EEGs were less common in patients with ICP &amp;gt;30mmHg (p=0.008). No differences were found in given treatments like vancomycin, acyclovir, or steroids between ICP groups. ICU admission, vasopressor support, and ventilation needs were comparable, though patients with higher ICP had longer median hospital stays (12 days vs. 10 days, p=0.012) and mechanical ventilation (1.5 days vs. 0 days, p=0.005). Mortality and readmission rates showed no differences, but patients with higher ICP had worse Glasgow Outcome Scale (GOS) scores (61% vs. 46%, p=0.045).Table 3.Management Approaches and Outcomes in Encephalitis Patients Categorized by Opening Pressure LevelsAbbreviations: ICU, intensive care unit; GOS, Glasgow outcome scale. Conclusion This retrospective study on ICP in encephalitis across two centers emphasizes presentation variability and the need for standardized diagnostic and management protocols. Noted differences include ventilation duration, hospital stays, and GOS in patients with higher ICP.Figure 1.Breakdown of 647 cases of encephalitis, categorized by their determined etiologies and ICP measurements. The chart illustrates the distribution across three groups: OP not measured, OP &amp;lt;30mmHg, and OP ≥30mmHg, detailing the total number of cases alongside the percentages for each etiological category, including viral, bacterial, autoimmune, and unknown origins.CMV; Cytomegalovirus, EBV; Epstein-Barr Virus, HSV; Herpes Simplex Virus, JCV; JC Virus, MTB; Mycobacterium tuberculosis NMDA; N-Methyl-D-Aspartate, T. pallidum; Treponema pallidum, VGKC; Voltage-Gated Potassium Channel, WNV; West Nile Virus. Disclosures John Probasco, MD, Genentech: Study site investigator for multicenter study Rodrigo Hasbun, MD MPH FIDSA, Biomeriaux: Grant/Research Support|Biomeriaux: Honoraria

P-104. Impact of Sepsis-Induced Cardiomyopathy on Clinical Outcomes in Sepsis Patients

Abstract Background Despite the known impact of cardiac function on sepsis outcomes, there is limited understanding of how ejection fraction (EF) influences hospital mortality in patients with sepsis-induced cardiomyopathy. This study assesses the severity of cardiac dysfunction determined by echocardiography within the first 24 hours of sepsis diagnosis on hospital mortality. Methods In this retrospective cohort study, 2,504 patients diagnosed with sepsis and who underwent echocardiography within 24 hours were analyzed. Based on EF, patients were classified into normal (EF ≥ 50%), moderate dysfunction (30% ≤ EF &amp;lt; 50%), and severe dysfunction (EF &amp;lt; 30%). The primary outcome was hospital mortality. Multivariable logistic regression was employed to identify factors associated with increased mortality, adjusting for clinically and statistically significant variables. Results Among the study patients, 1,803 (72%) had a normal EF, 356 (14.2%) had moderate dysfunction, and 115 (4.6%) had severe dysfunction. The hospital mortality was significantly higher in the severe dysfunction group at 40.0%, compared to 29.5% in moderate and 25.7% in normal EF groups (P=0.023). In multivariable analysis, severe cardiac dysfunction, inappropriate initial antibiotic therapy, and certain sites of infection were significantly associated with increased hospital mortality. Conclusion The decreased EF among sepsis patients is correlated with increased organ failure and higher mortality rates compared to patients with normal cardiac function. Disclosures All Authors: No reported disclosures

Using a clinical decision support system to reduce excess driving pressure: the ALARM trial

BackgroundPatients at need for ventilation often are at risk of acute respiratory distress syndrome (ARDS). Although lung-protective ventilation strategies, including low driving pressure settings, are well known to improve outcomes, clinical practice often diverges from these strategies. A clinical decision support (CDS) system can improve adherence to current guidelines; moreover, the potential of a CDS to enhance adherence can possibly be further increased by combination with a nudge type intervention.MethodsA prospective cohort trial was conducted in patients at risk of ARDS admitted to an intensive care unit (ICU). Patients were assigned to control or intervention by their date of admission: First, the control group was included without changing anything in clinical practice. Next, the CDS was activated showing an alert in the patient data management system if driving pressure exceeded recommended values; additionally, data on the performance of the wards were sent to the healthcare professionals as the nudge intervention. The main hypothesis was that this combined intervention would lead to a significant decrease in excess driving pressure.ResultsThe 472 included patients (230 in the control group and 242 in the intervention group) consisted of 33% females. The median age was 64 years; median Sequential Organ Failure Assessment score was 8. There was a significant reduction in excess driving pressure in the augmented ventilation modes (0.28 ± 0.67 mbar vs. 0.14 ± 0.45 mbar, p = 0.012) but not the controlled mode (0.37 ± 0.83 mbar vs. 0.32 ± 0.8 mbar, p = 0.53). However, there was no significant difference between groups in mechanical power, the number of ventilator-free days, or the percentage of patients showing progression to ARDS. Although there was no difference in progression to ARDS, 28-day mortality was higher in the intervention group. Notably, the mean overall driving pressure across both groups was low (12.02 mbar ± 2.77).ConclusionsIn a population at risk of ARDS, a combined intervention of a clinical decision support system and a nudge intervention was shown to reduce the excessive driving pressure above 15 mbar in augmented but not in controlled modes of ventilation.

P-1854. Children with Congenital Heart Disease and PICS (Persistent Inflammation, Immunosuppression, and Catabolism Syndrome) Demonstrate Both Pro- and Anti-Inflammatory Cytokine Profiles

Abstract Background Patients with chronic critical illness have variable recovery from acute events, such as surgery or sepsis, and experience dysregulated inflammation, blunted immune responses, and recurrent infections. The development of persistent inflammation, immunosuppression, and catabolism syndrome (PICS) increases the risk of healthcare associated infections, poor wound healing, and indolent organ failure. The pathophysiology of PICS has not been characterized in critically ill pediatric populations, particularly those with congenital heart disease (CHD). Methods The PICASSO study is an ongoing, observational cohort study of immunologic dysregulation in children with CHD who undergo cardiopulmonary bypass for surgical repair. Three groups were defined in this preliminary analysis. Children with uncomplicated post-operative courses served as control participants. Group 1 includes children who underwent CHD repair and were anticipated to have prolonged recovery (n=6), and Group 2 includes children with culture-confirmed, post-operative infection (n=2). PICS was defined as having at least 2 of the following criteria: lymphocyte count &amp;lt; 1500 cells/mL, CRP &amp;gt; 10 mg/dL, and albumin &amp;lt; 3 mg/dL. Blood samples were collected weekly for up to one month in Groups 1 and 2; controls had one sample collected at discharge. Plasma cytokines were measured using a 25-plex panel (Human Immunotherapy Fixed Panel, Luminex®). Results Thirty-four samples from 15 patients were analyzed. Plasma cytokines analysis across groups is shown in Figure 1. While come cytokines were more abundant in Group 1 compared to Group 2 and controls (e.g., IL-9 and IP-10), no significant differences were observed. Next, we compared cytokine levels in participants with (n=4) and without PICS (n=11). Both IL-1Ra and IP-10 were increased among children with PICS (p=0.007 and p=0.012, respectively). Conclusion In a preliminary analysis of the first 15 patients in the cohort, children with CHD and PICS demonstrate increased plasma levels of both pro-inflammatory (IP-10) and anti-inflammatory (IL-1Ra) cytokines that mirror the clinical phenotype of PICS. Ongoing analysis includes immunophenotyping and immunometabolic profiling of peripheral blood mononuclear cells. Disclosures C. Buddy Creech, MD, MPH, CommenseBio: Advisor/Consultant|GSK: Advisor/Consultant|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant

P-95. Predictors of bloodstream infection and its impact on mortality in septic arthritis: A 15-year review

Abstract Background Septic arthritis is often complicated by bloodstream infection (BSI), which can lead to metastatin infections and sepsis. In this study, we aimed to identify risk factors for septic arthritis-related BSI and assess its impact on clinical outcomes.Table 1.Comparison of clinical characteristics of septic arthritis patients with and without bloodstream infection. Methods A retrospective review spanning 15 years (January 2009 to May 2023) was conducted on patients diagnosed with septic arthritis. Data from patients with positive synovial fluid cultures were analyzed.Table 2.Laboratory and microbiologic findings of patients with septic arthritis according to bloodstream infections. Results Among 456 patients with septic arthritis, 16.8% (n=77) developed BSI. The 90-day mortality rate was significantly higher in patients with BSI compared with those without BSI (14.3% vs. 5.3%, P=0.004). Staphylococcus aureus was the most commonly identified organism in synovial fluid cultures and was associated with an increased risk of BSI (adjusted odds ratio [aOR], 2.20; 95% confidence interval [CI], 1.15-4.34; P=0.019). Independent risk factors for BSI included higher Sequential Organ Failure Assessment (SOFA) score (aOR, 1.23; 95% CI, 1.06–1.44; P=0.009), lymphopenia (aOR, 2.84; 95% CI, 1.38–6.15; P=0.006), and elevated C-reactive protein (CRP, mg/dL) levels (aOR, 1.07; 95% CI, 1.05–1.10; P&amp;lt; 0.001). Age ≥70 years (aOR, 3.96; 95% CI, 1.49–11.85; P=0.009) and higher SOFA score (aOR, 1.36; 95% CI, 1.12–1.67; P=0.002) were significant predictors of 90-day mortality, although BSI itself was not.Table 3.Multivariable analysis of risk factors for bloodstream infection and 90-day mortality in patients with septic arthritis.Variables with a P-value &amp;lt;0.05 in the univariable analysis were included in the multivariable analysis. Conclusion Mortality in patients with septic arthritis was primarily associated with systemic sepsis resulting from BSI rather than the BSI itself. Understanding the relationship between septic arthritis-related BSI and clinical outcomes can aid physicians in managing systemic infections and improving patient care.Figure 1.Distribution of causative organisms of septic arthritis. Disclosures All Authors: No reported disclosures

Association between enteral carboxymethyllysine intake and daily glycemic variability in critically ill adults: A retrospective cohort study.

Advanced glycation end-products (AGEs) can enter patients' circulation through exogenous sources, such as enteral nutrition formulae. Circulating AGEs, specifically carboxymethyllysine, can promote insulin resistance and activation of pro-inflammatory pathways leading to oxidative stress, cell death, and organ failure. Suboptimal kidney function increases the risk of elevated circulating AGEs because levels are controlled through urinary excretion. Our aim was to determine associations between carboxymethyllysine intake and glycemic control as well as clinical outcomes in critically ill patients and explore these in the subset of patients with an acute kidney injury (AKI). This was a retrospective cohort study. Data were extracted from electronic medical records. Patients were eligible if they were ≥18 years and received enteral nutrition, with known carboxymethyllysine content, for ≥3 days. AKI was defined using the Kidney Disease: Improving Global Outcomes guidelines. Linear and logistic regression models were used to determine adjusted associations. Between 2015 and 2021, 2636 patients met the eligibility criteria, with 848 (32%) patients having an AKI. Most were male (n = 1752, 67%) with a median (interquartile range) Acute Physiology And Chronic Health Evaluation III score of 59 (45-77). For every 10-μmol increase in carboxymethyllysine provision, mean blood glucose increased by 0.05 mmol (95% CI, 0.03-0.07), and the odds of dying increased by 16% (odds ratio = 1.16; 95% CI, 1.06-1.27). A subgroup analysis indicated these associations persisted in patients with AKI but not in those without. Carboxymethyllysine intake was associated with increased mean blood glucose and odds of dying in our study cohort.

Gut microbiota and its impact on critical illness.

This narrative review discusses the mechanisms connecting gut dysbiosis to adverse clinical outcomes in critically ill patients and explores potential therapeutic strategies. In recent years, the study of microbiota in ICUs has gained attention because of its potential effects on patient outcomes. Critically ill patients often face severe conditions, which can compromise their immune systems and lead to opportunistic infections from bacteria typically harmless to healthy individuals. The relationship between aggressive medical treatments and microbiota composition remains unclear. Dysbiosis, characterized by reduced microbial diversity and the loss of beneficial bacteria, can lead to prolonged immunosuppression and increased pathogenic risks, contributing to infections and organ failure. Recent advancements in multiomics technologies have enhanced the understanding of host-microbe interactions and their implications in critical care. The microbiota plays an important role in shaping outcomes for critically ill patients. According to evidence, alterations in the gut and lung microbiota are associated with disease severity, mortality, and overall patient recovery. Evolving research opens possibilities for personalized medicine by tailoring treatments based on individual microbiota profiles, though clinical applications are still developing.

Evaluation of the Effect of Virgin Rice Bran Oil (VRBO) on DoxorubicinInduced Cardiotoxicity in Wistar Rats.

The usage of doxorubicin (DOX), an antineoplastic drug that is frequently used for the cure of cancer, is restricted to maximal doses due to its cardiac toxicity. Reactive oxygen species produced by DOX result in lipid peroxidation and organ failure, ultimately resulting in cardiomyopathy. Due to its high polyphenol content, virgin rice bran oil (VRBO) is a diet nutritional supplement with a strong antioxidant. This study aimed to assess the potential defense of VRBO against DOX-induced cardiotoxicity. VRBO and DOX injections were administered to thirty male Wistar rats for 42 days after being randomly assigned to five groups. The study demonstrated the cardioprotective effects of VRBO against doxorubicin (DOX)-induced cardiotoxicity. VRBO (0.71 and 1.42 ml/kg) significantly improved the heart-tobody weight ratio, reduced elevated serum CK-MB and LDH levels by 18.4% and 52.7%, respectively, and increased HDL by 43.1%. ECG parameters also improved, with reductions in QT interval (19%), ST interval (28%), and QRS complex (15%). VRBO enhanced systolic blood pressure (up to 21%) and heart rate (7.1%). Antioxidant markers showed notable recovery, with MDA levels reduced by 66.1%, while GSH, SOD, and catalase levels increased by 129.4%, 158.2%, and 84.8%, respectively. A cardioprotective benefit was found at middle and higher VRBO dosages. In order to demonstrate the effectiveness of VRBO as a cardioprotective medication, further research on dosage response and bioavailability is required.

Advances in allogeneic hematopoietic stem cell transplantation for Langerhans cell histiocytosis in children

Langerhans cell histiocytosis (LCH) is a disease caused by clonal expansion of CD1a+/CD207+ cells and is characterized by organ involvement and dysfunction. Treatment of LCH in children is risk-adapted, and multisystem LCH requires systemic therapy. Although systemic treatments such as chemotherapy and BRAF/MEK inhibitors have improved the cure rate of LCH, disease reactivation rates remain 30%, and eventually some patients progress to relapse-refractory LCH. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a promising salvage treatment strategy for children with relapse-refractory LCH. However, many questions such as the efficacy and indications of allo-HSCT, as well as suitable conditioning regimen are still undetermined for children with LCH. This review aimed to provide an update on advances in allo-HSCT for LCH in children, including indications, stem cell sources, conditioning regimens, chimerism, transplant-related complications, outcomes, and treatment of relapse.