bluuebunny/crossref_metadata_2025 huggingface dataset:
826. Decision to Treat Pneumocystis Jirovecii Pneumonia by Combining Molecular Diagnostics and Patient Specific Factors
Authors: Maro Anna W , Cuellar-Rodriguez Jennifer , Kline Ahnika , Das Sanchita , Hunsberger Sally
Published: November 2023

Background

Pneumocystis jirovecii pneumonia (PJP) diagnosis on immunocompromised patients with or without HIV has changed over time. Molecular methods have substituted microscopic methods that can be subjective, labor intensive, and require expertise. Additionally, they can be falsely negative in patients with lower fungal burden, such as transplant recipients and other immunocompromised hosts. Due to optimization of resources, our laboratory has now opted to offer only PCR based testing. We reviewed the clinical and laboratory data at our center, for PJP diagnosis prior to this change, given that we have concurrent results from a direct fluorescent antibody (DFA) assay and PCR test on samples for 16 years.

Methods

We utilized data from retrospective chart review of 402 patients with a positive PJP PCR and a simultaneous DFA assay. Complete medical records were available for 302 patients. We included baseline characteristics by age, sex, race/ethnicity, and comorbid condition such as hematological malignancy diagnosis of PJP, solid malignancy, HIV, primary immunodeficiencies, and other chronic illnesses. Samples were collected by BAL or induced sputum. Concordance of the two tests was recorded; proportions of underlying comorbidities, use of prophylaxis and having received treatment was also recorded in relation to the concordance of both tests. Mortality within 30 and 90 days of sample collection was compared with corresponding Ct values, and DFA factors.

Results

302 patients were included in the analysis (see table 1); 72% had a discordant result. 69% of patients with a discordant result were treated, compared to 99% of those with a concordant result. Patients with hematological malignancy were more represented and were more likely to have received treatment when discordant, than PLWH or other groups. The 30 and 90-day mortality was numerically similar among both groups.Table 1.Clinical and laboratory characteristics of patients with a positive PJP PCR and a simultaneous DFA assay. Variables are expressed as proportions, unless otherwise specified.

Conclusion

PCR is a very sensitive tool to detect PJP, and in the era of decreased availability microscopy studies, clinical data evaluation such as patient population, and net state of immunosuppression, in addition to a positive test, will need to be considered when deciding who requires treatment.

Disclosures

All Authors: No reported disclosures
835. Histoplasmosis in Western India: Shedding Light on a Potentially Underdiagnosed Disease – A Prospective Study from a Tertiary care centre
Authors: Ravindra Akshatha , Kumar Deepak , Naguthevar Santhanam , Bohra Gopal Krishana , Khatod Yash , T R Neetha , Sharma Shivang , Kaur Navneet , Meena Durga Shankar , Midha Naresh Kumar , Garg M K
Published: November 2023

Background

Histoplasmosis is a fungal infection caused by Histoplasma capsulatum, can range from pulmonary to disseminated infections. While it is endemic in certain regions of the world, including North and South America, Africa, and parts of Asia, it is considered rare in India. However, recent reports suggest an increasing incidence of histoplasmosis in India. This project aims to evaluate the prevalence of histoplasmosis in the non-endemic western part of India and to study its clinical profile.

Methods

This was a prospective cross-sectional study which was conducted between January 2022 – February 2023 in Medicine department, AIIMS Jodhpur after obtaining approval from Ethics Committee. Patients aged more than 18 years with clinically suspected disseminated histoplasmosis (PUO, pancytopenia etc.) was screened using a rapid lateral flow test – OIDx Histoplasma Capsulatum LFA Kit. Urine samples were collected from all participants. Additional samples such as Blood, cerebrospinal fluid (CSF), biopsies etc, were collected for further confirmatory tests from patients with positive urine Histoplasma test as part of routine clinical care.

Results

A total of 45 patients (29 males, 64.4%) with a mean age of 48.8 years (range, 20-78) were included. Urinary histoplasma was found to be positive in 15 patients (33.33%), 8 of whom were confirmed with histopathology. The most common risk factor among the patients was HIV (35.5%). The common symptoms observed were fever and weight loss (73.3%), followed by cough (53.3%). Disseminated histoplasmosis with hepatosplenomegaly was seen in nearly 46.6% of the cases, while adrenal involvement was seen in 33.3%. Skin lesions were observed in only one-third of the patients. All patients were treated with Inj Amphotericin B, followed by itraconazole based on their weight. Most patients responded well to the treatment, with only one mortality.

Table 1

Clinical features of Disseminated Histoplasmosis in our study

Conclusion

The prevalence of histoplasmosis was found to be significant, particularly among HIV-positive patients. These findings emphasize the importance of considering histoplasmosis in the differential diagnosis of patients with compatible symptoms, especially in HIV-positive patients, and the need for further studies to determine the true burden of this disease in India.

Disclosures

All Authors: No reported disclosures
836. Coccidioidomycosis in the Central U.S. – A Retrospective Case Series
Authors: Scott Brian M , Gordon Olivia , Sassine Joseph , Sahra Syeda , Bowman Deidra J , Higuita Nelson I Agudelo
Published: November 2023

Background

Known as Valley fever, coccidioidomycosis is a disease endemic to arid regions of the Western Hemisphere. In the Southwestern US, Coccidioides spp. may account for up to 20-25% of cases of community acquired pneumonia. Clinical manifestations vary widely, from asymptomatic infection to life-threatening disease, especially in immunocompromised hosts. Management can prove to be challenging, especially in disseminated disease; however, the overall mortality rate remains low. We describe the results of a single-center, retrospective case series over the last 20 years.

Methods

A list of patients was identified from medical records, pathology, and microbiology, utilizing diagnosis codes and the key words ‘coccidioidomycosis’ and ‘valley fever’. Chart review was conducted on each of these cases. Variables included patient demographics, comorbidities, travel to an endemic area, site of infection, diagnosis, treatment, and outcomes.

Results

A total of 33 patients were identified using the methods above; however, only 26 patients were included in our study. 7 patients were excluded due to limited medical records. Most patients identified were male, middle-aged, and Caucasian (table 1). The most common comorbidity was diabetes, and the most common site of infection was pulmonary, followed by central nervous system (table 1, table 2). Nearly all patients received systemic antifungals, and about half underwent surgery for treatment (table 2).

Conclusion

To our knowledge, this is the largest single-center case series of coccidioidomycosis from a non-endemic area. Although most of our patients had visited an endemic area, several cases may be native to Oklahoma, considered a non-endemic region, based on available information in the medical record. Diabetes mellitus was the most frequent comorbidity exhibited by our patient population supporting surveillance data of its association with severe disease. Compared to other case series of coccidioidomycosis, our patient population had higher rates of immunocompromise and had both a higher overall mortality and rate of disseminated disease.

Disclosures

All Authors: No reported disclosures
845. Clinical Outcomes in Patients Treated with High vs. Standard Dose Liposomal Amphotericin B for Invasive Mucormycosis
Authors: Valiante Sarah , Elshaboury Ramy H , Wu Tiffany , Reyes Fabiola , Lahoud Chloe , Franceschi Andres E , Koo Sophia , Letourneau Alyssa R , Hammond Sarah P
Published: November 2023

Background

Mucormycosis is a life-threatening invasive fungal infection associated with high mortality. Amphotericin B is first-line therapy; however, the benefit of high doses remains uncertain. The purpose of this study is to describe outcomes in patients treated with high dose versus standard dose liposomal amphotericin B (L-AMB) for mucormycosis.

Methods

This was a retrospective cohort study of adults ≥ 18 years treated with L-AMB for proven or probable invasive mucormycosis at Massachusetts General Hospital and Brigham & Women’s Hospital from 2016-2022. L-AMB dosing was based on clinician preference. Patients were excluded if L-AMB began > 7 days prior to admission. Patients were categorized per L-AMB dose: standard dose (all doses < 6 mg/kg) and high dose (≥ 6 mg/kg for at least one dose). The primary outcome was 6- and 12-week mortality.

Results

67 patients were treated with L-AMB for proven or probable mucormycosis during the study period: 57 with standard dose and 10 with at least 1 high dose of L-AMB. Baseline characteristics are shown in Table-1. More patients in the standard dose group had underlying hematologic malignancy. About one third of patients had underlying diabetes and this was evenly distributed between groups. Table-2 shows infection- and treatment-related details. Proven invasive mucormycosis was diagnosed in 51/57 (89%) and 6/10 (60%) patients in the standard and high dose groups, respectively. The most common site of infection in both groups was skin/bone. Approximately 35/57 (61%) and 8/10 (80%) patients in the standard and high dose groups, respectively, had surgical debridement. Mortality at 6- and 12- weeks and renal toxicity outcomes are shown in Table-3. In the entire cohort at 6- and 12 weeks death occurred in 25/67 (37%) and 33/67 (49%) patients, respectively; no difference in mortality was seen between the standard and high dose groups. There appeared to be no difference in renal outcomes, though more patients in the standard dose group required renal replacement therapy within 6-weeks of diagnosis.

Conclusion

We observed no difference in 6- and 12-week mortality among patients treated with L-AMB at standard and high doses for invasive mucormycosis. Mortality at 6- and 12-weeks of mucormycosis diagnosis remains high.

Disclosures

Ramy H. Elshaboury, PharmD, DayZero Diagnostics: Advisor/Consultant|Gilead, Inc: Grant/Research Support|Thermofisher: Grant/Research Support Sophia Koo, MD, SM, Aerium Therapeutics: Advisor/Consultant|GSK: Grant/Research Support|Merck: Grant/Research Support|Scynexis: Grant/Research Support Sarah P. Hammond, MD, F2G: Advisor/Consultant|F2G: Grant/Research Support|GSK: Grant/Research Support|Pfizer: Advisor/Consultant|Scynexis: Grant/Research Support|Seres therapeutics: Advisor/Consultant
862. Machine Learning to Differentiate Group A Streptococcal (GAS) from Non-GAS Pharyngitis Using a Custom Smartphone App
Authors: Hamdy Rana F , Nguyen Trong , Ansusinha Emily , Arjoune Youness , Dome Jeffrey S , Shekhar Raj
Published: November 2023

Background

Sore throat is one of the top three reasons for ambulatory pediatric visits in the United States. Approximately one-third of children with sore throat are diagnosed with GAS pharyngitis, for which antibiotics are indicated. Because symptoms and physical exam-based clinical prediction rules are insufficient to accurately diagnose GAS pharyngitis, laboratory testing is needed for conclusive diagnosis. Antibiotics are frequently overprescribed for pharyngitis, especially in the telemedicine setting where testing is not readily at hand. We developed a custom mobile app, StrepApp, to capture throat images and apply machine learning (ML) to distinguish GAS pharyngitis from other causes of sore throat.

Methods

We enrolled patients >3 years old presenting with sore throat in the Children’s National Emergency Department. Using StrepApp, we collected throat images and presenting clinical symptoms. We defined GAS pharyngitis as a positive microbiologic GAS test and absence of upper respiratory infection (URI) symptoms; non-GAS pharyngitis was defined as those with negative microbiologic tests. We excluded patients who had received an antibiotic active against GAS in the previous 48 hours, those whose captured images were of poor quality or those with incomplete data, missing labs, or a positive GAS test in a patient presenting with URI symptoms. For ML classification, Scale Invariant Feature Transform (SIFT) was applied to throat images. Visual features were combined with clinical symptoms as input into a support vector machine (SVM) classifier to make a GAS versus non-GAS determination (Figure 1). We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the trained classifier.

Results

Of 262 patients enrolled, 148 images were analyzed. Curated images were split into 77 training images and 33 test images (Figure 2). The overall accuracy of the SVM classifier was 93.9%. The sensitivity, specificity, PPV, and NPV were 50.0%, 96.8%, 50.0%, and 96.8%, respectively.

Conclusion

StepApp shows promise to distinguish GAS from non-GAS pharyngitis with high specificity. The small sample size of the database allowed only conventional machine learning. As the database expands, deep learning with superior results may be possible.

Disclosures

All Authors: No reported disclosures
864. Can Population Risk Factors be Directly Applied to Guide Individual Patient’s Diagnosis and Treatment in Clinical Practice? – the Need to Re-Direct Epidemiology Research for Clinical Application in the Future
Authors: Huang Chaorui C , Xu Hong
Published: November 2023

Background

The implementation of population risk factor-guided diagnostic approach and treatment regimen has been widely considered in clinical practice to treat individual patient. However, the meaning of these risk factors, which are primarily developed from population-based epidemiology studies and thus presented probability and risk/odds ratio, are hard to interpret in clinical settings for individual patient. In this study, we provided an example of risk analysis for COVID-19 early intervention, in which the diagnostic accuracy of a population risk factor-based treatment regimen and an individual risk factor-based treatment regimen were compared, and the associated benefits and costs were evaluated.

Methods

The treatment regimen guided by the population risk factors was defined as such, that every COVID-19 patient aged ≥65 years old, and/or with at least one of the pre-selected chronic co-morbid conditions will be given a 500 mg/8 mL dose of the monoclonal antibody therapy, Sotrovimab intravenous, to prevent fatal outcome. The individual risk factor-based treatment regimen was determined using logistic regression model. We set the cost of Sotrovimab as $315.00 per patient, and the total cost including medication, hospital and infusion center administration charges, and charges for medical staffs as $2,000.00 per patient.

Results

Our study showed that the treatment regimen guided by population risk factors had resulted in a large amount of patient misclassification, with only 51.9% overall diagnostic accuracy, which is close to a random chance. However, by using the precision approach we developed for individual patient, the diagnostic accuracy was improved to 75%. Population risk factor-based treatment regimen prevented 1,570 more patients from a fatal outcome, however, it added 8 million dollars of cost for Sotrovimab and overall additional 54 million dollars of total cost.

Conclusion

Population level risk analysis provided inadequate information for individual patient’s diagnosis and treatment in clinical practice. Future research needs to focus on developing personalized diagnostic and treatment approach. We anticipate the improved clinical prediction by adding additional laboratory biomarkers to the individual precision diagnostic approach we developed.

Disclosures

All Authors: No reported disclosures
865. Same Shift Susceptibility Testing of Cefepime-Taniborbactam and Cefiderocol Using The Selux Next-Generation Phenotyping System
Authors: Jimenez David , Baker Kristin , Spears Benjamin , Flentie Kelly , Roberts Kristen , Michaels Gabriel , Stern Eric
Published: November 2023

Background

Robust, efficient, and reliable antimicrobial susceptibility testing (AST) systems are an integral component of effective antibiotic treatment. Multi-drug resistant (MDR) bacteria continue to emerge at alarming rates, requiring continuous innovation and development of new antibiotics. Among the new promising treatments for severe bacterial infections caused by carbapenem-resistant gram-negative bacteria, Cefiderocol (FDC) and Cefepime-Taniborbactam (FTB) have emerged as two frontrunners. FDC is the only FDA-approved siderophore cephalosporin, and FTB pairs the fourth-generation cephalosporin Cefepime, with Taniborbactam, a novel beta-lactamase inhibitor. AST results are paramount when directing therapy for patients with MDR infections, yet there is an average 3-year delay between the approval of new antibiotics and 510k submissions for new agents on automated AST systems. This is typified by FDC, for which there are currently no FDA-cleared automated AST systems. Here we assess the accuracy of FDC and FTB AST results using the Selux Next-Generation Phenotyping System.

Methods

For both FTB and FDC susceptibility, AST was performed using the Selux AST system and compared to CLSI broth microdilution (BMD) reference method in either cation-adjusted Muller Hinton broth (CAMHB) or its Iron depleted counterpart (ID-CAMHB). FDC, was tested in ID-CAMHB across 44 total CDC AR-Bank carbapenem-resistant K. pneumoniae, A. baumannii, and P. aeruginosa species. 34 CDC AR-Bank Strains predominantly resistant (30/34) to Cefepime were used to assess FTB. For FDC Essential Agreement (EA) and Categorical Agreement (CA) relative to ID-CAMHB were determined according to FDA breakpoints. FTB breakpoints were based on FDA breakpoints for Cefepime. For both agents, a comparison of BMD and the Selux system was accessed by EA and CA.

Results

The Selux AST system produced MICs to FDC with an average accuracy of 98% EA and 98% CA in ID-CAMHB (Table 1). In FTB, the Selux AST system produced MICs with an average accuracy of 94% EA and 100% CA in CAMHB (Table 2).

Conclusion

These data demonstrate the ability of the Selux NGP system to provide accurate results for FDC and FTB. This is the first known demonstration of an automated AST system for these important new drugs.

Disclosures

David Jimenez, B.S., Selux Diagnostics: Employee Kristin Baker, PhD, Selux Diagnostics: Employee Kelly Flentie, PhD, Selux Diagnostics: Employee Kristen Roberts, BS, Selux Diagnostics: Stocks/Bonds Gabriel Michaels, n/a, Selux Diagnostics: Employee Eric Stern, PhD, Selux Diagnostics: Board Member|Selux Diagnostics: Ownership Interest
875. Development of a Cheap, Portable Assay to Rapidly Profile Resistant Bacterial Infections
Authors: Roach David , Bhattacharyya Roby P
Published: November 2023

Background

Antimicrobial resistant (AMR) bacterial infections pose a significant and growing health threat worldwide. The burden of these resistant infections is often most severe in lower income areas, where the medical infrastructure necessary for their diagnosis is lacking. The development of cost-effective and accessible diagnostic tools for the rapid identification of resistant infections in low-resource settings is crucial. Specific High-sensitivity Enzymatic Reporter Unlocking, or SHERLOCK, is a promising CRISPR-based system that can aid in the diagnosis of infections and support clinical decision making. Here, we present an assay termed BADLOCK (Bacteria and AMR Detection by SHERLOCK) that uses SHERLOCK technology to rapidly identify bacterial species and AMR genes on blood cultures.

SHERLOCK Schematic

Enzymatic activity of the Cas protein is turned on when the target gene is bound, which then activates reporter probes.

Methods

We combine isothermal amplification of gene targets with SHERLOCK-based detection into a single step, allowing for a streamlined workflow and a total time-to-detection of less than two hours. The assay targets the topA gene for species identification, which is highly conserved within species but has sufficient variability between them to allow for discrimination between even closely related pathogens. A panel of clinically important AMR genes, including CTX-M-15, mecA, and five canonical carbapenemases, is also targeted to provide information on resistance profiles.

BADLOCK Targets

Gene targets included in the BADLOCK assay.

Results

BADLOCK has high sensitivity and specificity for both AMR genes and species identification and leverages a lateral-flow platform to provide a simple visual readout. We are currently validating BADLOCK on a library of several hundred clinical isolates with known genetic backgrounds, including a large collection of carbapenem-resistant Enterobacterales, which are major contributors to the global burden of resistant infections.

Lateral Flow Assay Results

Lateral flow results. Strip 1 is the topA gene specific to K. pneumoniae. Strips 2-4 are AMR genes KPC, CTX-M-15, and MecA. Lane 5 is a positive control; lane 6 is a NTC with bottom banding. “+” and “-” symbols mark representative readouts.

Conclusion

We have developed an assay for the cheap, rapid detection of bacterial infections of the bloodstream capable of detecting common pathogens as well as a panel of AMR genes. Our work has the potential to improve the diagnostic landscape for resistant infections in low-and-middle-income countries, which would represent a major step forward in infectious disease treatment in these underserved areas.

Disclosures

All Authors: No reported disclosures
877. Diagnostic Values of Viral Target Enriched and Metagenomic NGS among Patients with Acute Undifferentiated Fever in Thailand
Authors: Yamaguchi Julie , Berg Michael G , Weiss Sonja , Phoompoung Pakpoom , Cloherty Gavin , Suputtamongkol Yupin
Published: November 2023

Background

Despite extensive lab testing, infectious agents were not detected in ∼50% of patients hospitalized for acute undifferentiated febrile illness (AUFI) at Siriraj Hospital, Bangkok, Thailand. Unbiased metagenomic Next Generation Sequencing (mNGS) enables detection of many microbes present in patient samples. Target enrichment for viruses in these libraries represents a highly sensitive and cost-effective approach for overcoming host background present in clinical specimens. Plasma collected from 440 patients with AUFI between 2014-2021 were analyzed by both viral target enrichment and mNGS to determine their diagnostic values for the identification of human pathogens.

Methods

Benzonase-treated plasma was extracted on an Abbott m2000 instrument. mNGS libraries were prepared from ds-cDNA and hybridized to CVRP probes (Twist Biosciences) covering > 15,000 strains of vertebrate viruses. Target enriched libraries were run on a MiSeq; mNGS libraries were sequenced on a NextSeq. Reads were processed by the SURPI or DiVir pipelines and viral reads were mapped in the CLC Bio Genomics Workbench.

Results

We identified viruses in 23% of our AUFI population using CVRP. mNGS increased viral detection to 26.8% and overall pathogen detection to 41.8%. Both methods identified relatively prevalent viruses such as Dengue, HIV-1, HBV, HAV and CHIKV, less common viruses such as Measles, HHV-6B, CMV, and PARV and emerging viruses such as SFTS virus with a high degree of correlation between NGS and clinical data. Bacterial pathogens identified by mNGS included Rickettsia typhi, R. felis and Capnocytophaga canimorsus. Identification of parasites P. falciparum and P. vivax was consistent with clinical presentations. mNGS failed to detect blood-culture positive patients with Klebsiella pneumoniae, Pseudomonas aeruginosa, and Streptococcus gallolyticus septicemia.

Conclusion

CVRP and mNGS demonstrated that viral and rickettsial infections were important etiologies for AUFI in Thailand. This data supports the current recommendation of empirical therapy with ceftriaxone and doxycycline or azithromycin in severe or hospitalized AUFI. Implications for proper management of AUFI include lower rates of unnecessary testing and antimicrobial use.

Disclosures

Julie Yamaguchi, BS, Abbott Labs: Patents|Abbott Labs: Employee|Abbott Labs: Stocks/Bonds Michael G. Berg, PhD, Abbott Laboratories: employee|Abbott Laboratories: Stocks/Bonds Sonja Weiss, BS, Abbott Laboratories: Employee|Abbott Laboratories: Stocks/Bonds Pakpoom Phoompoung, MD, Abbott Labs: Grant/Research Support|Abbott Labs: Mahidol University is a partner in the Abbott Pandemic Defense Coalition Gavin Cloherty, PhD, Abbott Labs: Patents|Abbott Labs: Employee|Abbott Labs: Stocks/Bonds Yupin Suputtamongkol, MD, Abbott Labs: Grant/Research Support|Abbott Labs: Mahidol University is partner in the Abbott Pandemic Defense Coalition
879. Host Response Classifiers Identify Infection and Illness Severity and Improve Antibiotic Decision-Making in Patients with Suspected Infections Presenting to the Emergency Department
Authors: Beltran Arianna , Chen Uan-I , Michelson Edward A , Steingrub Jay S , Humphries Roger L , Gill Jasreen K , Weissman Alexandra , Giamarellos-Bourboulis Evangelos J , Wright David W , Liesenfeld Oliver , Whitfield Natalie N
Published: November 2023

Background

Nonspecific presentation and limited diagnostic solutions of acute infections and sepsis in emergency departments (EDs) result in early antimicrobial administration at a cost to antimicrobial stewardship. We validated the host response classifiers, IMX-BVN-3b and SEV-3b, to determine bacterial and viral infection status and illness severity. We also assessed antibiotic over- and underuse.

Methods

We prospectively enrolled adult ED patients with suspected acute infections or sepsis with ≥1 vital sign abnormal across 7 sites. At enrollment, we surveyed treating physicians on infection probability and antibiotic prescribing. BVN/SEV-3b were calculated using NanoString nCounter® on PAXgene® blood samples. We compared BVN-3b likelihood of bacterial and viral infection to post-hoc clinical adjudication infection status and SEV-3b likelihood of severe outcomes to 7-day need for ICU care and 30-day mortality.

Results

Of 568 enrolled patients, 346 had consensus adjudications (131 bacterial, 52 viral, 1 coinfection, 162 noninfected). The BVN-3b area under the receiver operating curve (AUROC) for bacterial infections was 0.82 (95%CI 0.77-0.87), compared to 0.76 (95%CI 0.71-0.81) for procalcitonin (p = 0.011). BVN-3b AUROC for viral infections was 0.89 (95%CI 0.84-0.95). SEV-3b AUROC was 0.78 (95%CI 0.69-0.86) and 0.88 (95%CI 0.73-1) for 7-day ICU care and 30-day mortality, respectively. Of the 346, 226 patients had a pre-lab result physician questionnaire; of these, 110 patients received antibiotics. Of these, BVN-3b would have corrected 71% of antibiotic prescribing errors (34/48 overprescriptions and 13/18 underprescriptions).

Conclusion

BVN-3b and SEV-3b accurately identified bacterial and viral infections and risk status. If implemented in a rapid workflow, these tests may improve patient management and antibiotic prescribing, reducing healthcare costs in the ED.

Disclosures

Arianna Beltran, BS, Inflammatix: Internship Uan-I Chen, MS, Inflammatix: Stocks/Bonds Edward A. Michelson, MD, Inflamatix: Research expense reimbursement for sponsored clinical trial Alexandra Weissman, MD, Inflammatix Inc: Advisor/Consultant Evangelos J. Giamarellos-Bourboulis, PhD, D(ABMM), Abbot Product Operations AG: Grant/Research Support|Abbot Product Operations AG: Honoraria|bioMerieux: Grant/Research Support|bioMerieux: Honoraria|Horizon 2020 European Program: Grant/Research Support|Horizon Health European Program: Grant/Research Support|Sobi AB: Advisor/Consultant|Sobi AB: Grant/Research Support|Sobi AB: Honoraria Oliver Liesenfeld, MD, Inflammatix Inc.: Ownership Interest Natalie N. Whitfield, PhD, D(ABMM), GenMark Dx/Roche: Employee|GenMark Dx/Roche: Stocks/Bonds|Inflammatix: Employee|Inflammatix: Stocks/Bonds
880. Diagnostic Testing Sample-Type Preferences: Results From An International Survey On SARS-CoV-2
Authors: Akbarzada Sumaira , Narayanan Nithya , Salzano Leah , Tobik Emily R , Megiel Sarah , Duni Craig , Choate Brittany , Harper Samantha S , Wyllie Anne L
Published: November 2023

Background

Diagnostic strategies rapidly evolved during the COVID-19 pandemic in response to the unprecedented worldwide testing demand. The public’s perception in regards to testing has also evolved. Testing remains essential for understanding the current state of the pandemic and directing efforts and resources. The purpose of this study was to better understand the public view regarding clinical sample types to inform future diagnostics development and surveillance planning.

Methods

To assess SARS-CoV-2 testing preferences, we distributed a Qualtrics survey via social media and email to connections in > 100 countries. The questionnaire covered testing preferences and key demographic information. Python was used to analyze the raw data.

Results

From 03/30-11/30/2022, a total of 2,094 responses were received from Africa (22%), Asia (8%), Europe (22%), North America (27%), Latin America and the Caribbean (9%), the Middle East (7%), and Oceania (6%). Participants were 55% female, 44% male, and 1% non-binary and ranged in ages (18-24, 13%; 25-34, 27%; 35-44, 23%; 45-54, 16%; 55-64, 14%; 65+, 8%). Education level and employment was skewed with 52% holding a graduate degree and 26% holding a bachelor’s degree; 27% were scientists/researchers and 29% were healthcare workers. Assuming equal accuracy between COVID-19 test types, respondents most preferred oral sample collection and least preferred methods involving coughing. The most preferred sample collection method varied by region (nasal swab = Europe; oral swab = Africa, North America, Oceania; saliva = Asia, Latin America and the Caribbean). In the majority of regions, saliva based testing was the most preferred method by parents and guardians for their children.

Conclusion

This study identified a preference for oral sample types for the detection of SARS-CoV-2, with saliva collection from children preferred by parents. Large-scale, easily accessible diagnostic testing is vital for detecting, monitoring, and containing outbreaks of respiratory pathogens; utilization of oral sample types supports the feasibility of this, if individuals are then more likely to test. Results from this study should be considered when new testing practices are designed to encourage maximum participation from individuals and improve community health.

Disclosures

Anne L. Wyllie, PhD, Co-Diagnostics: Board Member|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support
881. Saliva-Based, Extraction-Free PCR Testing For The Detection Of Key Respiratory Pathogens
Authors: Allicock Orchid M , Lin Tzu-Yi , Fajardo Katherine , Yolda-Carr Devyn , Hislop Maikel , Wang Jianhui , Zuniga Denora , Platt William D , Tuohy Beth , Peno Chikondi , Wyllie Anne L
Published: November 2023

Background

Efforts to control and monitor transmissible infectious diseases rely on large-scale screening often impaired by logistically difficult or invasive sample collection. The use of saliva as a non-invasive sample type could alleviate bottlenecks encountered in mass testing strategies. Having extensively demonstrated saliva as a sensitive sample type for SARS-CoV-2 detection, we sought to validate the approach for other common upper respiratory tract pathogens.

Methods

We modified our RNA-extraction-free SARS-CoV-2 PCR test for multiplexed detection of four additional respiratory viruses (“SalivaDirect+”): influenza A/B, RSV, and hMPV, and singleplex detection of pneumococcus. Stability of detection was tested after storage of saliva from pathogen-positive patients at +4°C, room temperature (∼19°C) and 30°C for 72 hours. De-identified saliva samples were collected from consenting adults ≥ 18 years of age with respiratory symptoms, requiring nasopharyngeal-swab based SARS-CoV-2 testing at Yale Health, New Haven, CT, USA. Saliva samples from individuals testing nasopharyngeal-swab negative for SARS-CoV-2 at the clinical laboratory were stored at -80°C until further processing in the research laboratory.

Results

We confirmed the limit of assay detection at 4 copies/µl for each target. We confirmed pathogen detection remained stable at +4°C, room temperature and 30°C for up to 72 hours. From the symptomatic testing site, 804 nasopharyngeal swabs tested negative for SARS-CoV-2; their paired saliva samples were tested with the SalivaDirect+ assay. Of those, 17 (2.1%) tested positive for one of the viruses targeted (influenza A, n=7; RSV, n=4; hMPV, n=6). No samples tested positive for influenza B. For influenza A and RSV, detection by SalivaDirect+ was comparable to testing following RNA extraction but detection of hMPV was less sensitive, even following assay modifications. In singleplex testing, 87 (10.8%) samples tested positive for pneumococcus.

Conclusion

We expanded a low-cost, open-source saliva-based PCR test for detection of other common respiratory pathogens. By testing saliva samples from symptomatic, SARS-CoV-2-negative adults, we detected common respiratory viruses which were otherwise missed in testing focused solely on SARS-CoV-2.

Disclosures

Anne L. Wyllie, PhD, Co-Diagnostics: Board Member|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support
928. Concordance with Institutional Guidelines for Letermovir Cytomegalovirus Infection Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplant Recipients
Authors: Peterson-Weber Alex , Palisano Nicholas , Alonso Carolyn D
Published: November 2023

Background

Cytomegalovirus (CMV) is an opportunistic infection in immunocompromised patients associated with significant morbidity and mortality. Letermovir (LET) is used for prophylaxis for CMV-seropositive allogeneic hematopoietic stem cell transplant (HSCT) recipients. An institutional guideline was developed to provide guidance on the appropriate use of letermovir. The purpose of this study was to determine overall concordance with letermovir institutional guidelines and to identify areas for quality improvement.

Methods

Our evaluation included adult hospitalized patients admitted from November 2019 to July 2022 for allogeneic HSCT who received LET, identified via medication administration records. The primary outcome was concordance with the institutional guideline criteria for use, as outlined in Figure 1. Secondary outcomes included incidence of breakthrough CMV viremia, use of concomitant HSV prophylaxis, and appropriate management of drug interactions (Figure 1).

Results

We identified 41 patients who received LET during the study period. After excluding patients who received a solid organ transplant, 32 patients were included in the study. The median time to LET initiation post-transplant was 7 days and the median time to discontinuation was 105 days post-transplant. Overall, 9 patients (28%) were fully concordant with our guidelines. Of the remaining patients, reasons for discordance are summarized in Table 1, mainly driven by continuation of LET >110 days post-transplant (n=12, 37%). Three (9%) patients received LET despite CMV recipient negative serostatus (CMV R-). Breakthrough CMV viremia occurred in 3 patients (9%). All patients received concomitant HSV prophylaxis and had drug interactions managed appropriately.

Conclusion

Our evaluation identified a lower than expected rate of letermovir guideline concordance, primarily related to the recommended duration of drug therapy. We found that our guideline has supported providers to ensure that concomitant HSV prophylaxis is given and drug interactions are managed appropriately. A further investigation into the use of letermovir in CMV R- subjects and a cost analysis is planned to guide future institutional guideline updates.

Disclosures

Carolyn D. Alonso, MD, Academy for Continued Healthcare Learning: Honoraria|AiCuris: Advisor/Consultant|American Society of Healthcare Pharmacists: Honoraria|Cidara Therapeutics: Advisor/Consultant|Clinical Care Options: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support
931. Host PFKFB3-dependent glycolytic reprogramming as a broad-spectrum antiviral strategy
Authors: Yuan Shuofeng , Ye Zi-Wei , Chu Hin
Published: November 2023

Background

The current therapeutic arsenal against viral infections remains poor, with limited spectrum of coverage and appears inadequate to face the emergence of pandemic and antiviral resistance. This study aims to develop a broad-spectrum antiviral strategy for rapid epidemic control and early treatment with better clinical outcome.

Methods

To investigate the in vivo change of glucose homeostasis under infectious circumstances, we carried out a time-course monitoring of blood glucose concentration in pdmH1N1-infected BALB/c mice and revealed that impairment of glucose tolerance and insulin sensitivity were caused when compared with the mock-infection control. To explore the change of gene expression file upon virus infection, we first plotted the pdmH1N1 virus replication kinetics in human primary bronchial/tracheal epithelial cells (hBTECs), followed by mRNA gene expression profiling of the key glycolytic enzymes at 0hpi, 6hpi and 24hpi, respectively. To discover potential enzymatic inhibitors/modulators of host glycolysis for antiviral treatment, we screened a small molecular compound library with 344 glycolysis compounds on pdmH1N1 infected hTBECs, followed by secondary validation to confirm the dose-dependent virus inhibition at non-toxic concentrations.

Results

Significant higher blood glucose level was detected in infected-mice with either glucose or insulin supplement, which suggested that host glucose metabolism, in particular the glycolysis homeostasis, were disrupted upon influenza virus infection. We also identified Glucose transporter 4 (GLUT4), enolase 2 (ENO2), monocarboxylate transporter 2 (MCT2), MCT4 and 6-phosphofructo-2-kinase (PFK2, also named PFKFB3) the most perturbed genes at 24hpi. KAN0438757, a potent and selective inhibitor of the metabolic kinase PFKFB3, was shown to be antiviral effective against both H1N1 and EV-A71 viruses in human primary cells. Moreover, Kan exhibited broad-spectrum antiviral activity in ZIKV-infected Huh7 cells and SARS-CoV-2 infected Caco-2 cells.

Metabolic profiling reveals significant perturbations of host glucose homeostasis after influenza A virus infection.

Conclusion

Host PFKFB3-dependent glycolysis pathway with broad-relevance to multiple virus replications, which might be a vulnerable host target for antiviral intervention.

Disclosures

All Authors: No reported disclosures
Long-lasting developmental effects in rat offspring after maternal exposure to acetamiprid in the drinking water during gestation
Authors: Longoni Victoria , Kandel Gambarte Paula Cristina , Rueda Lis , Fuchs Julio Silvio , Rovedatti María Gabriela , Wolansky Marcelo Javier
Published: November 2023

Neonicotinoids (NNTs) are a class of insecticides proposed to be safe for pest control in urban, suburban, and agricultural applications. However, little is known about their developmental effects after repeated low-dose exposures during gestation. Here, we tested a dose considered subthreshold for maternal toxicity in rats (6 mg/kg/day) by assessing several morphological, biochemical, and neurobehavioral features in preterm fetuses and developing pups after maternal administration of the NTT acetamiprid (ACP) dissolved in the drinking water during gestational days (GD) 2–19. The exploratory evaluation included monitoring maternal body weight gain, fetal viability, body weight and sex ratio, cephalic length, neonatal body weight and sex ratio, metabolic enzymes in the placenta, maternal blood and fetal liver, and anogenital distance and surface righting response during infancy. We also used the circling training test to study the integrity of the associative-spatial-motor response in adolescence. Results showed no consistent findings indicating maternal, reproductive or developmental toxicity. However, we found ACP effects on maternal body weight gain, placental butyrylcholinesterase activity, and neurobehavioral responses, suggestive of a mild toxic action. Thus, our study showed a trend for developmental susceptibility at a dose so far considered subtoxic. Although the ACP concentration in environmental samples of surface water and groundwater has been mostly reported to be much lower than that used in our study, our results suggest that the ACP point of departure used in current guidelines aimed to prevent developmental effects may need to be verified by complementary sensitive multiple-endpoint testing in the offspring.
Impact of Pretreatment Weight Loss on Radiotherapy Utilization and Clinical Outcomes in Non–Small Cell Lung Cancer
Authors: Alvarez Christian M. , Aliru Maureen , Gannavarapu Bhavani S. , Song Tidie , Gilmore Linda Anne , Olaechea Santiago , Gomez Daniel R. , Ahn Chul , Infante Rodney E. , Iyengar Puneeth
Published: November 2023

Background:

Cancer cachexia is a syndrome of unintentional weight loss resulting in progressive functional impairment. Knowledge of radiation therapy utilization in patients with cancer cachexia is limited. We evaluated the use of curative and palliative-intent radiation for the management of patients with non–small cell lung cancer (NSCLC) with cachexia to determine whether tumor-directed therapy affected cachexia-associated outcomes.

Methods:

Using an Institutional Tumor Registry, we evaluated all patients with stages of NSCLC treated at a tertiary care system from 2006 to 2013. We adopted the international consensus definition for cachexia, with staging designated by the registry and positron emission tomography. Radiotherapy delivery and intent were retrospectively assessed.

Results:

In total, 1330 patients with NSCLC were analyzed. Curative-intent radiotherapy was utilized equally between patients with cachexia and non-cachexia with stages I to III NSCLC. Conversely, significantly more patients with stage IV disease and cachexia received palliative radiotherapy versus those without (74% vs 63%, P = 0.006). Cachexia-associated survival was unchanged irrespective of tumor-directed radiation therapy with curative or palliative intent. In fact, pretreatment cachexia was associated with reduced survival for patients with stage III NSCLC receiving curative-intent radiotherapy (median survival = 23.9 vs 15.0 mo, P = 0.009). Finally, multivariate analysis identified pretreatment cachexia as an independent variable associated with worsened survival (hazard ratio = 1.31, CI: 1.14,1.52).

Conclusion:

Patients with advanced NSCLC with cachexia received more palliative-intent radiation than those without weight loss. Tumor-directed therapy in either a curative or palliative approach failed to alter cachexia patient survival across all stages of the disease. These findings offer critical information on the appropriate utilization of radiation in the management of patients with NSCLC with cachexia.
Impact of intestinal microenvironments in obesity and bariatric surgery on shaping macrophages
Authors: Leyderman Michael , Wilmore Joel R. , Shope Timothy , Cooney Robert N. , Urao Norifumi
Published: November 2023

Obesity is associated with alterations in tissue composition, systemic cellular metabolism, and low-grade chronic inflammation. Macrophages are heterogenous innate immune cells ubiquitously localized throughout the body and are key components of tissue homeostasis, inflammation, wound healing, and various disease states. Macrophages are highly plastic and can switch their phenotypic polarization and change function in response to their local environments. Here, we discuss how obesity alters the intestinal microenvironment and potential key factors that can influence intestinal macrophages as well as macrophages in other organs, including adipose tissue and hematopoietic organs. As bariatric surgery can induce metabolic adaptation systemically, we discuss the potential mechanisms through which bariatric surgery reshapes macrophages in obesity.
Quality Improvement Practices and Resources Targeting Firearm Injuries: A Survey of U.S. Pediatric Trauma Centers
Authors: Wurster Lee Ann , Herndon Michele , Seastrom David , Fritzeen Jennifer , Mitchell Kara , Schmid Moe , Rumsey Kelley
Published: November 2023

BACKGROUND:

The increase in firearm injuries at U.S. pediatric trauma centers is a national public health crisis. This spike in penetrating trauma has challenged even the most mature pediatric trauma centers.

OBJECTIVE:

This project aims to identify U.S. pediatric trauma center best practices for the evaluation and resources dedicated to pediatric firearm injuries.

METHODS:

This study used an exploratory cross-sectional survey design using a study-specific questionnaire. An electronic survey was distributed to 159 verified U.S. pediatric trauma centers targeting patients younger than 15 years with firearm injuries from 2017 to 2021. Trauma approaches to injury prevention, advocacy, and common performance improvement events were surveyed. A follow-up survey provided a drill-down on the top three performance improvement events.

RESULTS:

A total 159 surveys were distributed, of which 63 (40%) submitted partial responses and 32 (20%) completed the initial survey in full. A 49% increase in pediatric firearm injuries occurred between 2019 and 2020. Eighty-six percent of the trauma centers identified at least one to two opportunities for improvement events related to firearm injuries, with most of these events requiring a tertiary level of review. The top three performance improvement events included the massive transfusion protocol/fluid resuscitation, emergency department procedures, and operating room resource availability.

CONCLUSIONS:

This study provides the first known examination of U.S. pediatric trauma center quality improvement efforts to address the crisis of pediatric firearm injuries. Our results indicate that most pediatric trauma centers are engaged in quality improvement and resource enhancement to combat firearm injuries.
Reexamining “psychosocial clearance”: A procedural framework for psychosocial evaluation in liver transplantation
Authors: Winder Gerald Scott , Fernandez Anne C. , Perumalswami Ponni V. , Mellinger Jessica L. , Clifton Erin G.
Published: November 2023

Psychosocial and “nonmedical” phenomena are commonly encountered in liver transplantation (LT) evaluations. They are simultaneously crucial decision-making factors and some of the most difficult and controversial clinical matters clinicians confront. Epidemiology, societal trends, and the preponderance of psychological and behavioral factors underpinning common end-stage liver diseases ensure that LT teams will continue to encounter highly complex psychosocial patient presentations. Psychosocial policies, practices, and opinions vary widely among clinicians and LT centers. Liver clinicians already report insufficient psychosocial expertise, which creates a large gap between the stark need for psychosocial expansion, improvement, and innovation in LT and the lack of accompanying guidance on how to achieve it. While the clinical domains of an LT psychosocial evaluation have been well-described, few articles analyze the procedures by which teams determine candidates’ “psychosocial clearance” and no conceptual frameworks exist. This article proposes a framework of core domains of psychosocial evaluation procedures, common pitfalls, and practical improvement strategies.