bluuebunny/crossref_metadata_2025_split huggingface dataset:
302. Using Severe Acute Respiratory Syndrome Coronavirus-2 Spike Protein Antibody Serology in addition to the ISARIC 4C Risk Score to Better Discriminate Adverse Clinical Outcomes in Hospitalized Patients with Coronavirus Disease 2019.
Authors: Goh Wilson , Nicholas Ngiam Jinghao , Chhabra Srishti , Sim Meng Ying , Tambyah Paul Anantharajah , Cross Gail Brenda , Chew Nicholas W S , Sia Ching Hui 
Published: December 2022

Abstract

Background
The Coronavirus disease 2019 (COVID-19) pandemic continues to threaten many countries globally. Large-scale vaccination exercises have helped to reduce transmission and severity of disease. We sought to modify an existing clinical score (the ISARIC-4C mortality score) to include serological status to better prognosticate hospitalized patients with COVID-19.

Methods
We examined the first 1781 consecutive hospitalized patients with polymerase chain reaction (PCR) confirmed COVID-19 in a tertiary academic centre. We divided the study population into those requiring intensive care and those who did not require throughout their inpatient stay. Baseline characteristics examined include medical comorbidities, vaccination status, SARS-CoV-2 serology spike protein, duration of fever and haemodynamics were compared. Adverse outcomes were defined as patients who required intensive care or mortality. Performance of the risk scores were measured by the area under receiver operating characteristic curves (AUC) in predicting adverse outcomes.

Results
The 55 patients requiring intensive care during their inpatient stay tended to have persistent fever beyond 72 hours and had lower titres of spike protein antibodies. (58.9 (±105.3) U/mL vs 144.2 (±116.2) U/mL, p = 0.007). A high spike protein antibody titre &gt;75 U/mL was independently protective for adverse outcomes (adjusted OR 0.15, 95% CI 0.04-0.53), even after adjusting for the ISARIC-4C score and the presence of persistent fever. Adding the serological status and presence of persistent fever to the ISARIC-4C score improved its performance in predicting adverse outcomes (AUC 0.84, 95% CI 0.78-0.89).

Conclusion
Addition of the SARS-CoV-2 serology spike protein titre and prolonged fever to the ISARIC-4C mortality score helps to better prognosticate adverse clinical outcomes in hospitalized patients with COVID-19.

Disclosures
All Authors: No reported disclosures.
311. Modeling Diagnostic Testing Strategies for SARS-CoV-2 to Minimize Societal Costs and Return People to Work
Authors: Zavala Sofia , Cox Gary M , Belknap Robert W , Smith Becky A , Lewis Sarah S , Polage Christopher R , Turner Nicholas A , Stout Jason E 
Published: December 2022

Abstract

Background
The shift to more transmissible but less virulent strains of SARS-CoV-2 has altered the risk calculation for infection. Particularly among young adults, the economic burden of lost work due to isolation exceeds the economic burden of morbidity due to infection. Testing strategies must adapt to these changing circumstances.

Methods
We modeled six testing strategies to estimate total societal costs for symptomatic people 18-49 years old: isolation of all individuals with no testing, rapid antigen test (RAg), RAg followed by a second RAg 48h later if first negative, RAg followed by a polymerase chain reaction (PCR) if negative, RAg followed by a PCR if positive, and PCR alone. We calculated costs for hypothetical cohorts of 100 symptomatic healthcare workers tested with each strategy; we included testing costs, lost wages, and hospitalization costs for the index, secondary, and tertiary cases. Key assumptions were 5% prevalence of infection, sensitivity of first/second RAg 40/80% with 97% specificity, PCR sensitivity/specificity 95/99%, all individuals isolate at symptom onset, are tested the same day, and isolate for 5 days if positive. RAg results were available the same day, PCR results were available the next day (Figure 1). One-way sensitivity analyses were performed for RAg sensitivity (20-80%) and positivity rate (1-80%).

Results
The least expensive strategy was RAg alone (Figure 2). This was primarily driven by its low sensitivity, which reduced lost wages at the expense of missing cases. At a threshold for RAg sensitivity lower than 29%, PCR testing alone became the cheapest strategy. When the positivity rate was &gt; 6% confirming a negative RAg with a PCR became the cheapest strategy, closely followed by PCR alone. At a positivity rate of &gt; 29%, isolation without testing was cheapest followed by confirming a negative RAg with a PCR and by the serial RAg test strategies (Figure 3).

Conclusion
In relatively young, healthy populations, a single rapid test was the least expensive strategy when the positivity rate was &lt; 6%, testing that included PCR became cheapest at intermediate positivity, and empiric isolation was cheapest at positivity &gt; 29%. Calibrating SARS-CoV-2 test strategies based on epidemiology may save societal costs.

Disclosures
Nicholas A. Turner, MD, MHSc, Aperio: Advisor/Consultant.
317. Use cases for rapid antigen-detecting tests for COVID-19 screening and surveillance: a systematic review
Authors: Anand Apoorva , Bigio Jacob , MacLean Emily , Underwood Talya , Pai Nitika Pant , Carmona Sergio , Schumacher Samuel G , Toporowski Amy 
Published: December 2022

Abstract

Background
Testing remains critical to controlling the COVID-19 pandemic. Antigen-detecting rapid diagnostic tests (Ag-RDTs), which can be used at the point of care, have the potential to increase access to COVID-19 testing, particularly in settings with limited laboratory capacity. This systematic review synthesized literature on specific use cases and performance of Ag-RDTs for detecting SARS-CoV-2, for the first comprehensive assessment of Ag-RDT use in real-world settings.

Methods
We searched three databases (PubMed, EMBASE and medRxiv) up to 12 April 2021 for publications on Ag-RDT use for large-scale screening and surveillance of COVID-19, excluding studies of only presumptive COVID-19 patients. We tabulated data on the study setting, populations, type of test, diagnostic performance, and operational findings. We assessed risk of bias using QUADAS-2 and an adapted tool for prevalence studies.

Results
From 4313 citations, 39 studies conducted in asymptomatic and symptomatic individuals were included. Of 39 studies, 37 (94.9%) investigated lateral flow Ag-RDTs and 2 (5.1%) investigated multiplex sandwich chemiluminescent enzyme immunoassay Ag-RDTs. Six categories of testing initiatives were identified: mass screening (n=13), targeted screening (n=11), healthcare entry testing (n=6), at-home testing (n=4), surveillance (n=4) and prevalence survey (n=1). Sensitivity and specificity values by testing category are shown in the table. Ag-RDTs were noted as convenient, easy-to-use, and low cost, with a rapid turnaround time and high user acceptability. Risk of bias was generally low or unclear across studies.

Conclusion
During the first year of the COVID-19 pandemic, Ag-RDTs were used across a wide range of real-world settings for screening and surveillance of COVID-19 in both symptomatic and asymptomatic individuals. Ag-RDTs were fast and simple to run, but due to their often low sensitivity, careful consideration must be given to their implementation and interpretation. Ag-RDTs have subsequently been rolled out more broadly and recommended for COVID-19 self-testing.

Disclosures
Talya Underwood, MPhil, Oncotherapeutics: Medical writing.
318. A Pain in the Neck: Cervical Pyomyositis, a Rare Case of Extraintestinal Nontyphoidal Salmonellosis Further Characterized by Whole-Genome Sequencing.
Authors: Haroun Pishoy , Yang Shangxin , Adamson Paul C , Sakona Ashlyn N 
Published: December 2022

Abstract

Background
Nontyphoidal salmonellosis (NTS) is the second-most common foodborne illness in the US, but extraintestinal manifestations are rare. We describe a case of sternocleidomastoid (SCM) pyomyositis, a rare entity, caused by Salmonella enterica, further delineated by whole-genome sequencing (WGS).
A 55 year old male with liver cirrhosis and uncontrolled type-II diabetes mellitus presented with a six-day history of an enlarging left-sided neck mass. He had no fevers, chills, night sweats, nausea, vomiting or diarrhea. He had recently returned from Saudia Arabia with exposures to camels, bats and lemurs. He did not consume raw foods or dairy products.
Physical exam revealed normal vital signs and a large firm neck mass. Labs were notable for leukocytosis and hyperglycemia. Neck computed tomography revealed a 6 cm heterogeneous mass inseparable from the left SCM. He required repeated drainage procedures; histopathology revealed skeletal muscle with inflammation, but no malignancy. Blood and procedural cultures grew Salmonella group B. He was treated with ceftriaxone then trimethoprim-sulfamethoxazole. Follow-up 4 weeks after presentation revealed only residual induration.

Methods
WGS was performed using Illumina MiSeq. Genotype and antimicrobial resistance markers were identified using MLST, KmerFinder and ResFinder on Center of Genomic Epidemiology. Virulence factors were identified using VFanalyzer.

Results
The bacteria was identified as Salmonella enterica subspecies enterica serovar Typhimurium and typed as ST19, the major phylogroup of Typhimurium globally. Characteristics associated with invasive NTS (iNTS) identified by WGS included genes encoding Type III secretion system and Invasin A. Other virulence factors included fimbrial adherence determinants, macrophage inducible genes, and an intracellular toxin SpvB. Resistance genes included aac(6')-Iaa, which confers resistance to tobramycin and amikacin, and qnrB19, which predicts resistance to ciprofloxacin. However, no quinolone resistance-related mutations were detected in gyrA, gyrB, parC and parE genes.
AMR Genes
Antimicrobial resistance genes identified by whole-genome sequencing of the Salmonella isolate.

Conclusion
Patients with uncontrolled diabetes are at increased risk of iNTS with or without associated diarrhea. WGS can identify additional factors that may influence morbidity and resistance.

Disclosures
All Authors: No reported disclosures.
319. Clinical accuracy and utility of plasma microbial cell free DNA NGS for the diagnosis of invasive aspergillosis in patients with hematologic malignancy and COVID-19
Authors: Lee Ki Hyun , Yeom Joon-sup , Choi Jun Yong , Ku Nam Su , Jeong Su Jin , Kim Jung Ho , Ju Lee Se , Kim Jinnam , Kim Chang Hyup , Lee Jung Ah , Jang Ji Eun , Won Dongju , Shin Saeam , Lee Seung-Tae , Ahn Jin Young 
Published: December 2022

Abstract

Background
Invasive aspergillosis (IA) is a great threat to the severely immunocompromised and patients with coronavirus disease (COVID-19). However, diagnosis of IA is often difficult due to need for invasive biopsy and low sensitivity of other diagnostic tests. Next-generation sequencing (NGS) of plasma cell free DNA (cfDNA) can be a novel non-invasive diagnostic modality. We evaluated the clinical accuracy and utility of microbial cfDNA NGS for the diagnosis of IA in patients with hematologic malignancy (HM) and COVID-19.

Methods
A single-center prospective study of plasma microbial cfDNA NGS was conducted in a tertiary-care hospital in South Korea. We enrolled adult patients with HM and COVID-19, who suspected IA and performed conventional diagnostic tests for IA. The results of NGS were compared with the diagnosis of IA through conventional methods. IA cases were diagnosed according to EORTC/MSG definitions in patients with HM, and modified AspICU criteria in patients with COVID-19. (Figure 1). Figure 1.Flow chart for the participant selection method used in this study

Results
Between March 2021 and January 2022, a total of 33 participants (22 [64.7%] male, median age 66.0 [50.5, 72.0]) were enrolled;19 participants with HM and 15 with COVID-19 were analyzed (Figure1 and Table1). In participants with HM, aspergillus cfDNA was detected in 100% of both proven (1/1) and probable (12/12) IA cases, and 33.3% of both possible (1/3) and no IA (1/3) cases. In participants with COVID-19, 46.2% of probable IA (6/13) showed positive aspergillus cfDNA. Detection rate of aspergillus cfDNA was significantly higher in proven/probable IA cases in participants with HM compared to participants with COVID-19. (100% vs 46.2%, p=0.005) (Figure 2). As shown in Table 2, among proven/probable IA cases, participants with positive aspergillus cfDNA showed significantly higher rate of having uncontrolled hematologic disease, receiving stem cell transplantation and recent chemotherapy. In three participants with HM, non-aspergillus strains confirmed by cfDNA NGS were in accordance with pathogens identified through conventional culture methods. Table 1.Baseline characteristics of participants suspected of invaisve aspergillosis performing microbial cell free DNA NGSFigure 2.cfDNA detection rate in participants with suspected fungal infection according to the EORTC/MSG or modified AspICU diagnostic criteria

Conclusion
Detection of aspergillus cfDNA showed high concordance in the results of conventional diagnostic methods in proven/probable IA of patients with HM and could be a helpful non-invasive approach to IA diagnosis in those populations.

Disclosures
All Authors: No reported disclosures.
327. Understanding Current Clinical Scenarios for Plasma Microbial Cell-free DNA Diagnostic Testing toward Informing Diagnostic Stewardship
Authors: Lau Constance , Matthew Hill T , Messacar Kevin , Nolte Frederick S , Park Sarah Y 
Published: December 2022

Abstract

Background
Plasma microbial cell-free (mcfDNA) testing has emerged as a promising tool for unbiased detection of pathogens in patients with suspected infections. A systematic evaluation of the patient populations in which this test is used may provide insight into applications for clinical use. We describe demographic and clinical characteristics of patients tested with plasma mcfDNA linked to the Premier Healthcare Database (PHD).

Methods
A retrospective cross-sectional analysis was conducted using the PHD: a US hospital-based, service-level, all-payer database containing information primarily from geographically diverse communities, teaching hospitals, and health systems. Patients with plasma mcfDNA testing 4/1/2018-12/31/2020 were deterministically linked to the PHD. Patient characteristics were collected via chargemaster data, ICD-10 diagnosis, and procedure codes. Immunocompromised (IC) status was identified using 2021 Agency for Healthcare Research (AHRQ) ICD-based definitions. The AHRQ Elixhauser Comorbidity Index score was derived using ICD-10 codes to indicate comorbidity burden.

Results
A total of 778 patients in the PHD underwent plasma mcfDNA testing during the study period, 88% of whom were tested in the inpatient setting (Table 1). Thirteen percent had a discharge diagnosis of sepsis with an unspecified organism. Median inpatient length of stay was 10 days with a median of 4 days from time of admission to plasma mcfDNA testing. Forty-seven percent of patients were IC with a majority (62%) having an Elixhauser score ≥ 7, suggestive of a high comorbidity burden (Table 2). Two hundred forty-nine (32%) inpatients required intensive care unit (ICU) level care for a median 15 days.

Conclusion
Plasma mcfDNA testing is primarily being used in the inpatient setting in a wide variety of clinical scenarios, particularly among seriously ill and immunocompromised patients, who tend to have broad infectious disease differentials and high morbidity and mortality risks. Understanding the current populations, indications, and timing of mcfDNA testing may contribute to developing diagnostic stewardship research and guidelines to optimize impact on clinical outcomes.

Disclosures
Constance Lau, MPH, Karius, Inc.: Current employee|Karius, Inc.: Stocks/Bonds T. Matthew Hill, PharmD, PhD, Karius, Inc: Paid employee|Karius, Inc: Stocks/Bonds Frederick S. Nolte, PhD, D(ABMM), F(AAM), Karius: Employee.
329. Bedside Inoculation of Blood Culture Bottles Does Not Improve Ascites Culture Positivity Rate in Spontaneous Bacterial Peritonitis
Authors: Brehm Tyler , Al Mohajer Mayar , Lasco Todd M 
Published: December 2022

Abstract

Background
Prior research demonstrates increased positivity rate for ascites cultures in spontaneous bacterial peritonitis (SBP) when directly inoculated into blood culture bottles at bedside, versus the “conventional method” - transportation of ascitic fluid in a sealed syringe to the laboratory, centrifuging, and plating on Chocolate, Blood, and MacConkey’s agars and in a Schaedler broth. We hypothesized that collection of ascites via direct inoculation into blood culture bottles would improve ascites culture positivity rate in SBP when compared to prior methods.

Methods
In November of 2021, our institution implemented a policy in which all ascites cultures were directly inoculated into blood culture bottles at bedside. We retrospectively reviewed all ascites cultures collected from May of 2021 through April of 2022, including all cultures with an absolute neutrophil count of greater than 250 cells/mm3. We excluded all samples from patients with secondary bacterial peritonitis and all samples collected in November. If a patient had multiple samples that met inclusion criteria, only the first was included for analysis. Our primary outcome was positivity rate of cultures pre- and post-implementation of this new policy.

Results
1375 ascites cultures were collected. Of these, 52 met our inclusion criteria. These patients were on average 58 years old (range 33-74), 50% female, with a median MELD of 25.5 (range 8-40). The conventional method was positive in 7/37 (18.9%) cultures, and direct inoculation of blood cultures in 1/15 (6.67%), p = .27.

Conclusion
As opposed to the previous literature, we detected no difference in positivity rate between the conventional method of ascites culture compared to direct inoculation of blood cultures at the bedside. This difference from prior literature may be due to differences in time to inoculation, our smaller sample size, or overfilling of the bottles during inoculation.

Disclosures
All Authors: No reported disclosures.
332. Broad range PCR of pleural fluid improves diagnosis of bacterial pneumonia complicated by parapneumonic effusion
Authors: Upadhyayula Shankar 
Published: December 2022

Abstract

Background
Bacterial pneumonia complicated by a para pneumonic effusion is frequently encountered in hospitalized patients. However, identifying the etiology of pneumonia remains elusive. Published data report rates of bacteremia ranging from 13-26% among patients with pneumonia complicated by parapneumonic effusion. Good quality sputum samples are difficult to obtain in children. Culture of pleural fluid is helpful, but most patients are already pretreated before a specimen is obtained limiting utility. Nucleic acid assays of pleural fluid have reported sensitivities from 40-80%. We wanted to review our experience with pleural fluid nucleic acid assay at Akron childrens hospital

Methods
Using help from our laboratory data support team, we retrospectively reviewed the records of all pleural fluid isolates that were sent out to Washington University Medical Center for 16 S rRNA sequencing (broad range polymerase chain reaction assay). The review covered a 8-year time period ranging from January 2014 to March 2022. Negative blood and pleural fluid cultures were a prerequisite before the send out for nucleic acid assay.

Results
A total of 29 pleural fluid samples were sent out for 16S rRNA sequencing. 22 of these had a detectable target. This translated into a yield of about 75%. The following table summarizes our findings.

Conclusion
In our experience, nucleic acid assay of the pleural fluid is valuable in making a bacteriological diagnosis of pneumonia with para pneumonic effusion. Its benefit remains in patients pretreated with antibiotics. For the individual patient it may help narrow antibiotic therapy. At an institutional level it would allow for developing guidelines for empiric antibiotic management. However, in most institutions’ nucleic acid assay of pleural fluid remains a send out test and optimizing workflows to reduce turnaround time remains a challenge.

Disclosures
All Authors: No reported disclosures.
333. Clinical Impact of a Multiplex Rapid Diagnostic Panel in Critically Ill Patients
Authors: Esplund Jayda , Taylor Alex D , Stone Tyler , Palavecino Elizabeth , Kilic Abdullah , Luther Vera , Beardsley James 
Published: December 2022

Abstract

Background
The BioFire FilmArray® Pneumonia Panel® (PP) is a rapid diagnostic test that detects select bacterial and viral respiratory pathogens and the presence of certain antimicrobial resistance genes within 75 min of testing. Starting Nov 2021 respiratory specimens from all adult ICU patients (pts) with quantitative cultures (cx) obtained by bronchoalveolar lavage (BAL) or tracheal aspirate (TA) were automatically tested with PP. The purpose of this study was to evaluate the clinical impact of the PP.

Methods
This single-center, retrospective cohort study compared patients prior to (PRE) (Jan - Mar 2021) and after (POST) (Jan - Mar 2022) implementation of the PP. Adult ICU pts with a quantitative cx obtained by BAL or TA during the study periods were reviewed in random order until 25 pts from each study month meeting study criteria were identified (75 pts in each cohort). Pts with another infection other than bacteremia with the same causative pathogen requiring antibiotics (ABX) in the previous 14 days through 5 days after specimen collection or pts who died within 5 days after specimen collection were excluded. ABX therapy for the 5 days after cx collection was evaluated. The primary outcome was time to first ABX change based on microbiologic test results. Secondary outcomes included ABX days of therapy (DOTs), time to adequate therapy, and potential vs actual ABX changes made based on the PP in POST cohort.

Results
PRE pts were a median of 54 yrs old and 56% female compared to 59 yrs and 32% female in POST cohort. Median time to first ABX change based on microbiologic data was 50.3 hrs PRE vs 21.2 hrs POST (p=0.0006). 56 (75%) of POST ABX regimens were eligible for change based on PP results; actual change occurred in 30 (54%) of these regimens (ABX de-escalation in 23 and escalation in 7). Median ABX DOTs were 8 PRE vs 6 POST (p = 0.07). For the pts with ABX changes made based on PP results, median time to first ABX change was 10 hrs. For pts who were initially on inadequate therapy, time to adequate therapy was 67 hrs PRE vs 37 hrs POST.

Conclusion
The PP was associated with decreased time to first ABX change and fewer ABX DOTs. The PP may have had a larger impact if a higher percentage of potential ABX changes were implemented. The PP may be a useful ABX stewardship tool.

Disclosures
All Authors: No reported disclosures.