bluuebunny/crossref_metadata_2025_split huggingface dataset:
781. “Rashional” Infectious Diseases Training: A “Dermatology for Infectious Diseases Fellows” Pilot Curriculum Evaluation
Authors: Rockney Danica , Melia Michael T 
Published: November 2023

Abstract

Background
Rashes are common among patients with infections. A prior survey of United States adult infectious disease (ID) fellowship program directors showed that most respondents (55/90; 61%) do not have a formal dermatology curriculum for their fellows and 76% (41/54) were interested in incorporating an externally produced dermatology curriculum if made available to them. To address this education gap, a “Dermatology for the ID Fellow” curriculum was created.

Methods
During the 2022-2023 academic year, a “Dermatology for the ID Fellow” curriculum was piloted with the 11 fellows in the Johns Hopkins adult ID fellowship program. The curriculum included two lectures, multiple asynchronous board-style questions, and three knowledge assessments (Figure 1). Curricular objectives were evaluated by pre-, mid-, and post-curriculum knowledge assessments. Descriptive data analysis was performed. This study was IRB exempt.

Results
The response rates for the pre-, mid-, and post-curriculum knowledge assessments were 91%, 64%, and 55% respectively. The response rate of asynchronous questions averaged 63% across all participating fellows (range 13%-100%). Most fellows correctly identified primary rash morphologies by verbal description (88% correct) and photographs (96% correct). At the end of the curriculum, 50% (4/8) of the fellows ranked their comfort level in approaching cutaneous manifestations of infections as higher than before the curriculum, with 38% (3/8) staying the same. More fellows used a systematic approach to unknown rashes after the curriculum (83%; 5/6) as compared to before the curriculum (30%, 3/10) (Figure 2). There was no improvement in fellows' ability to determine a differential diagnosis based on rash appearance. Overall, 100% of the fellows felt like the lectures presented new and important knowledge.

Conclusion
Incorporation of a “Dermatology for ID Fellows” curriculum was viewed favorably. The curriculum increased the use of a systematic approach to a rash and helped some fellows improve comfort level in approaching a rash. Data from this pilot curriculum will inform subsequent iterations that may help increase the ability to develop infectious differentials based on rash appearance, addressing an important knowledge gap in ID fellowship training.

Disclosures
All Authors: No reported disclosures
811. A prospective pilot multicenter study of Aspergillus colonization in the nasal cavity as a surrogate marker of invasive aspergillosis among acute myeloid leukemia patients and allogeneic stem cell transplant recipients
Authors: Charoonrochana Natnai , Jinawath Natini , Santanirand Pitak , Jiaranaikulwanich Atisak , Taweewongsounton Aruchalean , Setthaudom Chavachol , Tanpaibule Tananun , Surin Dootsadeephorn , Damronglerd Pansachee , Limvorapitak Wasithep , Rungwittayatiwat Sirapat , Pinsai Subencha , Niparuck Pimjai , Rotjanapan Porpon 
Published: November 2023

Abstract

Background
Invasive aspergillosis (IA) is a common opportunistic infection in patients with acute myeloid leukemia (AML) and allogeneic stem cell transplant (SCT) recipients. Identifying at–risk patients may improve clinical outcomes when universal prophylactic therapy is not possible in a resource-limited setting. Aspergillus spp. colonization has been listed as a potential risk for infection development among patients with hematologic diseases, but this has not been explored in real-life clinical practice.

Objectives
To evaluate the correlation of Aspergillus spp. colonization and invasive aspergillosis development and to assess nasal wash galactomannan as a potential predictor for IA among AML patients and allogeneic SCT recipients.

Methods
A prospective pilot study at four tertiary care hospitals in Thailand was conducted from April 2021 to January 2023. All AML individuals requiring induction chemotherapy and patients admitted for a conditioning regimen for allogeneic SCT were enrolled. Nasal wash fluid was obtained for galactomannan and fungal culture to assess Aspergillus spp. colonization before chemotherapy. The patient’s demographic and relevant data were retrieved. All patients were monitored for IA development and the need for antifungal use for IA treatment.

Results
25 AML patients and nine allogeneic SCT recipients were included. A nasal wash fungal culture positive for Aspergillus spp. was identified in 3/34 patients. Eighteen (52.9%) patients were diagnosed with invasive aspergillosis after a six-month follow-up, 15/25 among AML patients, and 3/9 among allogeneic SCT. 8 patients (23.5%) had nasal wash galactomannan &gt;0.46, and 5/8 patients had IA. The cut-off value of nasal wash fluid galactomannan of 0.46 provided a sensitivity of 55.56% and specificity of 78.57% in diagnosing IA in AML patients.

Conclusion
The incidence of Aspergillus spp. colonization by the traditional culture-based method was low at treatment initiation and did not suggest future IA development in this study. However, nasal wash galactomannan may help predict future IA development in AML patients, but due to low sensitivity may limit its role in actual clinical practice at a larger scale. Further studies are needed to verify the best strategy to predict the risk of IA in this population.

Disclosures
All Authors: No reported disclosures
821. Positive Follow-Up Blood Culture in Candidemia and Ocular Involvement
Authors: Iqbal Hamail , Nikolic Dejan , Palacios Carlo Foppiano 
Published: November 2023

Abstract

Background
Candidemia can lead to ocular complications, including endophthalmitis and chorioretinitis. Prompt management of such ocular diseases is paramount due to the risk of blindness. Management of candidemia usually includes a dilated ophthalmic exam; however, there are concerns regarding the utility of performing ophthalmic exams in all patients due to a low rate of ocular complications and lack of changes in medical management. Thus, there is a need for prognostic factors suggestive of ocular involvement that warrant a thorough ophthalmic examination. We sought to evaluate if positive repeat blood cultures are associated with ocular involvement in candidemia.

Methods
A single-center, retrospective chart review was conducted at an academic medical center. All candidemia cases from 2017 to 2022 were analyzed for demographics, culture results, treatment, inpatient ophthalmic exam findings, and mortality at discharge, at 30 days, and at 90 days. Descriptive statistics and Chi-Square tests were performed on the collected data.

Results
104 episodes of candidemia among 84 patients were included: the mean age was 54 years, 55% were male, 74% were Black, and 13.1% were Latino. The most common Candida species isolated was C. albicans (37%) and most patients were treated with micafungin (51%). 12% had visual symptoms and 84% underwent ophthalmic exams. 15% of the exams were concerning for ocular involvement: 5% endophthalmitis, 5% chorioretinitis, and 5% other infectious findings (Roth spots and other retinal lesions). There was no significant association between repeat positive blood culture results and development of endophthalmitis (p = 1.00), chorioretinitis (p = 0.93), or any ocular involvement (p = 0.97). Furthermore, no significant associations were found between repeat blood culture and death at discharge, 30 days, or 90 days.

Conclusion
No significant associations were found between repeat positive blood culture and ocular involvement in the setting of candidemia. Other indicators of ocular involvement in candidemia are needed to assess patients who would benefit from ophthalmic exam.

Disclosures
All Authors: No reported disclosures
830. Risk factors for late Pneumocystis jirovecii pneumonia in kidney transplant recipients: A Case-Control Study of United States Renal Data System Data
Authors: Mendoza Maria Alejandra , Vergidis Paschalis , Friedman Daniel Z P 
Published: November 2023

Abstract

Background
Organ transplant recipients are at increased risk of potentially life-threatening opportunistic infections, including Pneumocystis jirovecii pneumonia (PJP). Given the use of effective prophylaxis, PJP has become less common, especially during the first-year post-transplant. Recent data has shown that the risk of infection has shifted within the first 2 years after discontinuing prophylaxis. We aimed to determine risk factors for late posttransplant PJP using a national database.

Methods
Using the United States Renal Data System database, we performed a retrospective case-control study of patients who underwent kidney transplant from 1998 through 2019. To evaluate risk factors for late PJP, we performed logistic regression analysis by comparing characteristics between infected patients and their matched uninfected controls.

Results
We identified 407 cases with PJP and matched to 1628 controls (1:4). 60 (14.7%) of the cases occurred within one year post transplant and 347 (85.3%) patients were diagnosed after one year of transplant. In the late period, the median time between transplant and PJP diagnosis was 68.7 (IQR 28 -134.2) months. Seventy cases (20.1%) occurred between 12 and 24 months.
In multivariate analysis (table 1), risk factors for late infection included a higher Elixhauser Comorbidity Index (ECI), history of cytomegalovirus disease, older donor age, use of antilymphocyte agents, history of re-transplant and a longer time of hemodialysis prior to transplant. Of note, in the early period, we found that having a living donor was protective.
Multivariate analysis of risk factors for late Pneumocystis jirovecii pneumonia

Conclusion
Our findings highlight the importance of a timely transplant to mitigate the risk of post-transplant PJP in the late post-transplant period where prophylaxis is not routinely used. These results also raise the consideration of PJP prophylaxis in the late period in patients diagnosed with CMV disease, history of re transplant and recent use of antilymphocyte agents.

Disclosures
Paschalis Vergidis, MD, MSc, AbbVie: Advisor/Consultant|Ansun: Grant/Research Support|Cidara: Grant/Research Support|Scynexis: Grant/Research Support
841. An Evaluation of Outcomes and Hospital Readmissions Among Individuals with Candidemia in Connecticut (2019-2020)
Authors: Suschana Elizabeth , Banach David , Meek James , Clogher Paula , Correa Maria 
Published: November 2023

Abstract

Background
In addition to significant morbidity and mortality, sepsis is a leading cause of hospital readmission. Candidemia, a leading cause of sepsis, has a particularly high morbidity and mortality rate. Previous studies defined risk factors for poor outcomes and readmission after general sepsis. However, specific risk factors for readmission after candidemia are unknown.

Methods
The study is retrospective cohort study of adults in Connecticut with an episode of candidemia between 2019-2022 using statewide surveillance data. Individuals were classified based on primary outcome (died versus survived) at incident admission. Candidemia survivors were further classified by readmission status. A descriptive analysis of demographics, healthcare related factors, and readmission characteristics was performed in univariate and multivariate analyses to identify factors associated with mortality and readmission after an episode of candidemia.

Results
Among 347 candidemia cases, 226 (65.1%) survived the incident episode. Those who survived were more likely to be younger (age &gt; 65 = 70% vs age &lt; 65 = 59.2%; p = 0.036), have community-onset infections (84.4% community-onset vs 47.2% hospital-onset; p &lt; 0.001), and have an infection from a non-Candida albicans species (56.5% with C. albicans vs 70.8% with non-C. albicans; p = 0.006). In multivariate analysis, mortality was associated with hospital-onset infection [OR = 6.866, CI = 4.009 – 11.760]. Among survivors of the incident episode (n = 128), 56% were readmitted within 180 days post- incident episode. Of those readmitted, 13 (10.1%) were readmitted for a new incident candidemia episode. Readmission was associated with hospital-onset infection (OR=1.791, CI = 1.008 – 3.184).Table 1.Demographic and clinical factors of incident case outcome and readmissions, 2019-2020 (Abbreviated).* Indicates a significant p-value (p &lt; 0.05)Table 2.Multivariate analysis for age and class of infection by incident case outcome and readmission status

Conclusions
Individuals with candidemia have a high risk of mortality and readmission. Individuals with hospital-onset infection are at particularly high risk of mortality and subsequent readmission. Efforts to prevent hospital-onset candidemia are critical. Additional measures focused on individuals with risk factors for readmission are needed to reduce overall morbidity and mortality associated with candidemia.

Disclosures
All Authors: No reported disclosures
842. Histoplasmosis : An observational study from northern India in non-HIV population.
Authors: Swain Satish , Sekhar Paul Saurav , Aayilliath Adarsh , Maharatna Sayan , Mohan Lal Bhavesh , Punjadath Sryla , Shareef Imtiyaz , Singh Gagandeep , Xess Immaculata , Soneja Manish , Wig Naveet 
Published: November 2023

Abstract

Background
Globally around 40% of histoplasmosis has been reported in HIV population, with other risk factors being transplant recipients, immunosuppressive agents (steroids, TNF-alpha inhibitors) and extreme of ages. Histoplasmosis in India has mostly been reported from the Gangetic plains (Figure 1).

Methods
This current study was conducted in a tertiary care hospital of northern India between January 1, 2021 and December 31, 2022 to look at the epidemiology, clinical profile and treatment outcome of Histoplasmosis patients in a non-HIV cohort. This was a single centered, observational study. All patients with proven Histoplasmosis (according to EORTC/MSGERC 2019 criteria) were included.

Results
Baseline Characteristics: This study involved 20 patients with a mean age of 52.05 ± 10.87 years with 70% being male. All the patients were from endemic areas of Gangetic belt in India. Majority of the patients (80%) were immunocompetent (Table 1). All cases (100%) were diagnosed on histopathology.

Clinical and Laboratory Characteristics
The common reported complains were fever (75%), weight loss (70%), loss of appetite (75%), skin lesions (25%) and pain abdomen (15%). Mean duration of various symptoms was 3±1.29 months. Hepato-splenomegaly was seen in 45% of cases followed by adrenal involvement (40%), enlarged lymph nodes (35%), skin and oral mucosa involvement (25%) (Figure 2). Out eight patients had who adrenal involvement, five patients (25%) had isolated involvement based on imaging (CT/PET-CT). Cytopenias was seen in upto 75% cases with around 40% had deranged liver functions (Table 2). The most common syndromic diagnosis was progressive disseminated histoplasmosis (PDH) seen in 13 patients with a median age of 49 (30-76) years.

Treatment
13 patients (65%) received induction with Amphotericin B (liposomal) followed by switching to oral itraconazole and 7 patients (35%) got up front itraconazole. At a media follow up of 8 months, 40% of patients had completed treatment and one had patient died.

Conclusion
In a high tuberculosis endemic county like India, Histoplasmosis pose a diagnostic challenge. Although the median time to diagnosis is longer (delay in diagnosis), the overall outcome is good. Majority of our patients were younger immunocompetent individual.

Disclosures
All Authors: No reported disclosures
851. Metabolic Changes Contributing to Age-Associated Antifungal Tolerance in Cryptococcus neoformans
Authors: Yoo Kyungyoon , de Oliveira Natalia Kronbauer , Bhattacharya Somanon , Fries Bettina F 
Published: November 2023

Abstract

Background
Cryptococcus neoformans (CN) is a facultative intracellular pathogen that divides asymmetrically, resulting in different phenotypes of the mother and daughter cells. After 8-10 divisions, mother cells become more resistant to phagocytic killing by macrophages and resistant to antifungals. These resilient traits allow older CN cells to accumulate in the host during chronic infection. Across different pathogenic fungal species, age-associated mitochondrial changes help the cell adapt to various physiological stresses by altering metabolic regulation and ultimately promoting antifungal resistance.
Cryptococcus neoformans is the leading cause of fungal meningitis among immunocompromised populations

Methods
Ten GEN “old” CN cells were obtained by magnetic bead-based isolation and compared to 1-3 GEN “young” cells. Mitochondrial membrane potential, mass, reactive oxygen species (ROS), calcium, and morphology were evaluated by measuring the fluorescence of appropriate cellular dyes and fluorescent microscopy. ATP level was measured by using a kit measuring fluorescence. Lipid droplets and membrane sterols were quantified and visualized by using appropriate cellular dyes. Ergosterol and sphingolipid levels were quantified by a targeted lipidomic approach using LC-MS-MS.
Old mother cells can be separated and isolated by biotinylation and magnetic sorting

Results
Our data demonstrate old CN cells exhibit increased mitochondrial mass, calcium and ROS levels and decreased mitochondrial membrane potential. Additionally, while the mitochondria from young cells show the formation of tubular networks, the mitochondria of old cells exhibit fragmentation. Furthermore, old CN cells have &gt;5-fold higher ATP levels, which can fuel drug efflux pumps. Old cells show more lipid droplets that localize to the vacuole compared to young cells, which can serve as a cellular source of ATP. RT-qPCR analysis and lipidomic studies indicated changes in the synthesis of various ergosterols and sphingolipids, key lipids that are directly linked to pathogenesis and virulence mechanisms in CN.
Metabolic changes in old Cn cells contribute to antifungal tolerance

Conclusion
Our findings suggest that mitochondrial dysfunction of older cells is initially beneficial for CN as it promotes a metabolic switch to fatty acid oxidation and altered regulation of various classes of lipids. Increases in ATP production fuel efflux pumps and the export of azoles. This work furthers our understanding of the “old” CN cell phenotype that emerges during aging.

Disclosures
All Authors: No reported disclosures
856. CT-proET-1 and sFlt-1 as Predictors of Clinical Outcomes in a COVID-19 US Cohort
Authors: Atallah Johnny , Atallah Natalie , Panossian Vahe , Warren Hailey , Inlall Damian , Schwabe Andrej , Johannes Sascha , Wiemer Jan , Mansour Michael 
Published: November 2023

Abstract

Background
Several novel biomarkers have been studied in predicting clinical outcomes in patients with COVID-19. Our study aimed to study C-terminal proendothelin-1 (CT-proET-1) and Soluble fms-like tyrosine kinase-1 (sFlt-1) as predictors of clinical outcomes in a COVID-19 patient cohort from a US-based multicenter trial.

Methods
Data from the Boston Area COVID-19 Consortium (BACC) Bay Tocilizumab Trial was used in this study. Patients with biomarker determinations, and not admitted to the intensive care unit (ICU) on admission, were included. Median concentrations of CT-proET-1 (83.6 pmol/L) and sFlt-1 (81.3 pg/mL) were used as cutoffs in predicting clinical outcomes.

Results
Out of 169 patients, 10.7% mechanically ventilated or dead within 28 days of admission. CT-proET1 concentrations in patients who were mechanically ventilated or dead within 28 days were significantly higher than those who were not (median 119.6 vs 79.1 pmol/L, p=0.001), and higher in patients who were admitted to the ICU during hospitalization compared to those who were not (median 114.5 vs 80.6 pmol/L, p=0.005). Significantly higher sFlt-1 concentrations were seen in patients who were admitted to the ICU compared to those who were not (median 96.0 vs 80.7 pg/mL, p=0.041).
The sensitivity, specificity, PPV and NPV of CT-proET-1 with cutoff 83.6 pmol/L in predicting mechanical ventilation or death were 83%, 54%, 18%, and 96%, respectively, with an AUC of 0.75.
As for the sFlt-1 cutoff of 81.3 pg/mL in predicting mechanical ventilation or death, the sensitivity, specificity, PPV and NPV were 61%, 54%, 14%, and 92%, with an AUC of 0.59.

Conclusion
CT-proET-1 and sFlt-1 function as valuable novel biomarkers in predicting clinical outcomes in COVID-19, with lower levels predicting better outcomes. Further studies are needed to better understand their role in other upper respiratory viral illnesses.

Disclosures
Michael Mansour, MD, PhD, Thermofisher: Grant/Research Support
891. Cytomegalovirus Testing Rates Among Immunocompromised Adults, Adolescents, And Children In The United States
Authors: Jain Purva , Basnet Sandeep , Syed Sahar , Arakaki Brent , Mues Katherine E , Marcum Zachary , Diaz-Decaro John D 
Published: November 2023

Abstract

Background
Cytomegalovirus (CMV) is a latent virus that can cause morbidity and mortality among immunocompromised (IC) individuals. No studies have examined how CMV testing changed throughout the COVID-19 pandemic among IC individuals in the United States (US). This study aimed to estimate CMV testing rates among IC adults (18-94 years), adolescents (12-17 years), and children (0-11 years) during the COVID-19 pandemic.

Methods
This observational cohort study included insured individuals from the US and was conducted using administrative medical and pharmacy claims from HealthVerity from December 2017-May 2022. IC adults, adolescents, and children entered the cohort after 6 months of continuous enrollment and were followed until disenrollment or end of study period. CMV testing was captured using CPT codes (serology and PCR) and was limited to no more than 1 test per day with ≥6 days required between tests. The rate of CMV testing (per 100,000 person-months) was estimated over three time periods defined by key points in the COVID-19 pandemic: pre-COVID-19-era, 06/01/2018-03/31/2020; pre-vaccine-COVID-19-era, 04/01/2020-12/31/2020; and vaccine-COVID-19-era, 01/01/2021-05/31/2022.

Results
The sample included 735,251 IC adults, of whom 4.8% (N=35,391) had ≥1 CMV test over follow-up (median follow-up, 566 days); 12,203 IC adolescents, of whom 15.5% (N=1,896) had ≥1 CMV test over follow-up (median follow-up, 582 days); and 15,854 IC children, of whom 14.7% (N=2,324) had ≥1 CMV test over follow-up (median follow-up, 702 days). The mean rate of CMV tests per 100,000 person-months for IC adults was 1,660 in the pre-COVID-19-era, 1,040 in the pre-vaccine-COVID-19-era, and 983 in the vaccine-COVID-19-era. Similarly, rates of CMV testing declined among IC adolescents and children (adolescents: 7,391 in pre-COVID-19-era, 4,717 in pre-vaccine-COVID-19-era, and 4,219 in vaccine-COVID-19-era; children: 7,556 in pre-COVID-19-era, 4,467 in pre-vaccine-COVID-19-era, and 4,026 in vaccine-COVID-19-era). The highest testing rates were among those with a history of stem cell transplantation in all age cohorts.

Conclusion
CMV test utilization decreased during the COVID-19 pandemic era in the US and remained low through the early COVID-19 vaccine era.

Disclosures
Sandeep Basnet, MD, Moderna Therapeutics: Stocks/Bonds Brent Arakaki, BS, Aetion, Inc.: Employee Katherine E. Mues, PhD, Aetion, Inc.: Employee John D. Diaz-Decaro, PhD, MS, Moderna Therapeutics: Stocks/Bonds