bluuebunny/crossref_metadata_2025_split huggingface dataset:
1176. Quality of Life of Previously Healthy Subjects following Cryptococcal Meningoencephalitis
Authors: Dean Owen , Anjum Seher , Scott Terri , Ham Lillian , Powers John H , Snow Joseph , Williamson Peter 
Published: January 2021

Abstract

Background
Cryptococcal meningoencephalitis (CM) causes significant morbidity and mortality in HIV-negative, previously healthy populations. This group has significant disease sequalae including a fronto-subcortical syndrome, hearing loss, vision loss, and spinal arachnoiditis. However, the health-related quality of life (HRQOL) of this group of patients following microbial recovery from infection has not been reported.

Methods
We cross-sectionally defined the HRQOL of previously healthy individuals with CM seen at the NIH Clinical Center since 2013 and at least one year past diagnosis using the Quality of Life in Neurological Disorders (Neuro-QoL) project short forms. These forms assess domains such as anxiety, fatigue, depression, dexterity and mobility in patients with chronic neurological disease. Form scores were calculated for each domain and centered to a general or clinical United States population reference. Impairment was considered a subject score of least one half a standard deviation (SD) lower than the population reference average.

Results
Of 43 subjects with CM (mean age 48 years, 56% male, mean time from diagnosis 5.7 years), 91% had evidence of impairment in at least one HRQOL domain. Notable findings included self-reported impaired cognitive function in 53% and sleep disturbance in 56%. Impaired satisfaction with social roles and activities was present in 44%. Mobility and dexterity were impaired in 30% respectively. The number of impaired HRQOL domains was not significantly different in subjects with a history of neurosurgical intervention during hospitalization (mean no. impaired domains 4.4 vs. 3.3, P=0.43) or methylprednisolone treatment for post-infectious inflammatory response syndrome (4.3 vs. 3.4, P=0.63). Cerebrospinal fluid glucose levels on admission were negatively correlated with the number of impaired functional domains (rs=-0.33, P=0.05, n=38).
Patient reported quality of life domains following microbial recovery from cryptococcal meningoencephalitis. Box plots show median, 25th, and 75th percentiles.The gray dotted line represents the mean T-score (50) of the U.S. population reference for each Neuro-QoL domain. The yellow region designates mild symptoms or impairment (0.5-1.0 std below the population mean), orange, moderate (1.0-2.0), and red, severe (2.0-3.0). The asterisk* indicates measures that were centered to U.S. clinical reference population. All other domains were centered to a U.S. general population reference. Abbreviations: CNS, central nervous system, U.S., United States, ADL, activities of daily living, SRA, social roles and activities

Conclusion
This is the first report of HRQOL deficits in previously healthy individuals following microbial recovery from CM. These data reinforce and quantify the long-term morbidity of this disease and identify patient-centered outcomes for future interventional trials.

Disclosures
All Authors: No reported disclosures
1180. Seroincidence and Risk of Coccidioidomycosis Infection Among Active Duty Personnel Stationed at Naval Air Station Lemoore in the San Joaquin Valley of California
Authors: Ellis Graham C , Lanteri Charlotte , Hsieh Hsing-Chuan , Graf Paul , Sanders Terrel , Maves Ryan C , Deiss Robert 
Published: January 2021

Abstract

Background
Coccidioidomycosis ranges clinically from a self-limited respiratory illness to multi-organ dissemination. Based largely on skin testing from the 1940s, 60% of infections are thought to be asymptomatic. Limited Coccidioides seroincidence data support our understanding of the epidemiology and pathogenicity of this disease.

Methods
This retrospective cohort study tested 2000 U.S. military personnel for Coccidioides exposure after transfer to an endemic region of California between 2011 and 2017. The presence of IgG and IgM anti-Coccidioides antibodies were tested on pre- and post-transfer serum samples from the DoD Serum Repository to establish rates of seroconversion. Medical histories and participant demographics including race/ethnicity and military occupational specialty codes were collected from the electronic medical record and participants were stratified by a history of Coccidioides-specific or general respiratory illness based on ICD9/ICD10 coding.

Results
Thirty of 2000 participants tested newly positive for anti-Coccidioides antibodies after 12 months on station. Seroconversion incidence varied from 0.0-1.32 annually and overall 0.5 per 100 person years. Seroconverters were more frequently diagnosed with coccidioidomycosis or pneumonia than non-converters (p=0.027). No statistically significant association between demographic characteristics and seroconversion or disease was observed. Clinical disease was detected in only three seroconverters (10%).
Incidence Rate of Coccidioidomycosis Infection among Active Duty Stationed at NAS Lemoore, 2011-2017

Seroconversion Status by Cocci/Pneumonia Diagnosis Status

Conclusion
In this study Coccidioides seroincidence was similar to that observed by others, adding longitudinal evidence to epidemiologic assumptions about coccidioidomycosis. A trend toward increasing incidence over the course of the study is consistent with the classification of coccidioidomycosis as an emerging infectious disease. While transmission is typically related to exposure, we did not detect a difference based on military occupational specialty codes. Overall, rates of diagnosed disease in our cohort were lower than the historically-assumed 40% symptomatic rate, although this conclusion is limited by the retrospective nature of the study. Further clinical and epidemiologic coccidioidomycosis research, particularly in broader endemic regions, is warranted.

Disclosures
All Authors: No reported disclosures
1181. Spectrum and Risk Factors of Early Onset versus Late Onset Neonatal Candidemia from Pakistan
Authors: Rattani Salima , Jabeen Kauser , Farooqi Joveria , Hussain Ali Shabbir 
Published: January 2021

Abstract

Background
Candidemia leads to high morbidity and mortality especially in premature neonates from developing countries. We studied the spectrum and risk factors of candidemia in neonates with early onset disease (EOD) or late onset disease (LOD) which has not been extensively investigated in Pakistan. We also determined whether vaginal delivery is associated with candidemia in neonates with EOD.

Methods
A case control study was conducted at the Aga Khan University, Karachi, Pakistan. Cases (neonates with EOD) and controls (neonates with LOD) were identified from laboratory database for year 2014-2018, and for 2019 data was collected prospectively from laboratory during routine reporting of cultures at which time clinical information was gathered from the patient’s physician/guardian. Study was conducted after obtaining exemption from the ethical review committee.

Results
A total of 669 neonates with IC were identified, out of these 162 neonates had EOD while 507 had LOD. Chart 1 shows the year wise distribution and frequency of different C. species. Mean age of neonates with EOD and LOD was 1.7 and 12.2 days respectively. LOD in neonates was more likely to occur in male patients (COR 2.5, 95% CI 0.6-9.9) was and associated with use of carbapenems (COR 5.1, 95% CI 1.4-17.8). However, LOD had no correlation with non-C. albicans Candida sepsis (COR 0.6, 95% CI 0.1-6.3) as causative agent. EOD was more likely in patients delivered via vaginal delivery (COR 11.3, 95% CI 2.6-48.5).
Chart 1: Year wise distribution of Candida species in neonates with candidemia from 2014-2019

Conclusion
The trends for isolation of C. species in neonates showed a trend with C. tropicalis being more common C. species during the recent years. With the infrequent isolation of C. glabrata and C. krusei among other Candida species in this study, fluconazole may be considered a good empiric choice for neonates with suspected fungal sepsis.

Disclosures
All Authors: No reported disclosures
1183. A Prospective Epidemiological & Immunological Study of Cytomegalovirus infection in SLE Patients Receiving Immunosuppressant
Authors: Autto Suphanan , Pisitkun Prapaporn , Apiwattanakul Nopporn , Bruminhent Jackrapong 
Published: January 2021

Abstract

Background
Cytomegalovirus (CMV) infection has been emerging among autoimmune disease patients. CMV-specific cellular immunity has been shown to be correlated with CMV clearance in transplant recipients, however, this correlation has not been assessed in autoimmune disease patients. We aimed to investigate the epidemiology and clinical variables of CMV infection focused on CMV-specific cellular response of CMV infection in active systemic lupus erythematosus (SLE) patients receiving immunosuppressant.

Methods
A prospective cohort study of active SLE patients who received immunosuppressant and underwent preemptively monitored for CMV infection by quantitative real-time PCR (Abbott RealTime CMV assay). Clinical variables were collected. CMV-specific cellular immune responses were measured by an enzyme-linked immunosorbent assay (QuantiFERON-CMV®) and intracellular cytokine assay. Clinically significant CMV infection was defined as CMV disease or plasma CMV DNA loads &gt; 1,000 IU/mL.

Results
We included 45 active SLE patients in our cohort. Among 39 evaluable patients, there were 36 (92%) female patients with a median age of 28 (IQR 24-44) years. A median SLEDAI score was 16 (IQR 9-20). Seventy-four % had renal involvement. Methylprednisolone was the most common immunosuppressive regimen (94.9%). Thirty-six (92.3%) patients were CMV-seropositive. Clinically significant CMV infection occurred in 6 (25.6%) patients included asymptomatic CMV infection (79.3%), CMV syndrome (17.3%), and CMV tissue invasive disease (3.4%). Among 197 blood samplings, there were 16 (8.1%) episodes of clinically significant CMV infection. The distributions of QuantiFERON-CMV® status were reactive, non-reactive and indeterminate (33% vs. 44% vs. 22%; p = 0.56), respectively. The percentage of CMV-IE1-specific NKT cells in those with clinically significant CMV infection were lower than those without infection (0.18% vs. 1.93%, p = 0.03). In multivariate analysis, neurological involvement was associated with clinically significant CMV infection (OR 7.9; 95% CI 1.5-41.9, [p = 0.015]).

Conclusion
Active SLE patients with neurological involvement who received intense immunosuppression are at risk of CMV infection. Lack of CMV-specific NKT cell response tends to be associated with CMV infection.

Disclosures
All Authors: No reported disclosures
92. Utility of Sinus CT in the Evaluation of Patients with Febrile Neutropenia
Authors: Gurram Pooja , Almeida Natalia E Castillo , Vijayvargiya Prakhar , Grimont Christopher , Garrigos Zerelda Esquer , Khalil Sarwat , Ward Ruaa Al , Mahmood Maryam , Sohail M Rizwan 
Published: January 2021

Abstract

Background
The etiology of febrile neutropenia in patients with hematological malignancy is identified in only 20–30% of cases. Sinus computed tomography (CT) is often used, regardless of symptoms, to rule out rhinocerebral source of infection. There are no clear guidelines on when to perform sinus CT in this population. In this study, we evaluated the role of sinus CT in febrile neutropenic patients.

Methods
We retrospectively reviewed medical records of all adults (age ≥18 years) with febrile neutropenia (T≥ 38.3ºC, ANC &lt; 0.5 x 109/L) and hematological malignancies who underwent sinus CT from January 2014 to May 2020. We present the preliminary analysis of the impact of sinus CT findings on the management of febrile neutropenia.

Results
47 patients with a total of 56 episodes of febrile neutropenia met the inclusion criteria. The median age at presentation was 57 years (IQR: 42 - 68 years). The most common underlying malignancy was acute myeloid leukemia (51%), followed by myelodysplastic syndrome (19%). At presentation, 47% had refractory disease, 21% were newly diagnosed, 15% had relapsed, 15% were in complete remission, and 2% were in partial remission. Of the total 56 episodes, 29 (52%) had symptoms of rhinorrhea (20%), facial pain (14%), and sinus congestion (14%). The remaining 27 of 56 episodes (48%) had no sinus symptoms. Sinus CT was abnormal in 48 of 56 episodes (86%); the most common finding was mucosal thickening (47/48; 98%), followed by air-fluid levels (7/48; 14.5%), partial opacification (6/48; 12.5%), complete opacification (2/48; 4%), and bony invasion (2/48; 4%). The source of febrile neutropenia was attributed to the CT sinus findings in 9 cases (9/48; 29%), leading to a change in therapeutic management. All 9 patients were symptomatic, with evidence of necrosis in 22% (2/9) and purulence in 22% (2/9) on nasal endoscopy.
Table 1

Conclusion
Mucosal thickening is a frequent and non-specific imaging finding, particularly in patients without sinus symptoms. Sinus CT findings in patients with febrile neutropenia without sinus symptoms had no impact on clinical management. Consequently, sinus CT may be reserved for patients presenting with sinus symptoms.

Disclosures
M. Rizwan Sohail, MD, Aziyo Biologics (Consultant)Medtronic Inc (Consultant, Research Grant or Support)
1190. Dual-Plasmid Technology for Precision Genome Editing in Staphylococcus aureus
Authors: Reish Jennifer , Dey Somrita , Penewit Kelsi , Salipante Stephen J , Berti Andrew David 
Published: January 2021

Abstract

Background
Genetic manipulation of Staphylococcus aureus (both methicillin sensitive S. aureus, MSSA, and methicillin resistant S. aureus, MRSA) poses a technical challenge due to poor transformation efficiency, limited endogenous DNA repair activity, lineage-specific methylation patterns and intrinsic resistance to common selectable markers.

Methods
To address transformation efficiency we have optimized electrocompetent cell preparation and electroporation protocols for staphylococci. Further, we have improved a CRISPR counterselection platform that delivers a heterologous ssDNA recombinase and an inducible Cas9 endonuclease. When used for recombineering and counterselection, this strategy allows minimization of the number of elements necessary to transform in a single electroporation event. The Cas9 delivery platform has been modified to include a range of selectable markers including resistance to apramycin, erythromycin, kanamycin, nourseothricin, spectinomycin or trimethoprim.

Results
Overall electroporation efficiency increased by multiple orders of magnitude (&gt; 100×) using the optimized cell preparation protocol. The CRISPR delivery platform can be stably maintained in a repressed state for multiple generations and induced with anhydrotetracycline. We have introduced targeted mutations in multiple loci using this system with an average turnaround time of 12 days.

Conclusion
This improved dual-plasmid CRISPR platform is robust and allows the investigator to rapidly and specifically alter the genomes of staphylococci. These tools will facilitate the study of how specific genetic polymorphisms contribute to various phenotypes in S. aureus, including the virulence of MRSA.

Disclosures
All Authors: No reported disclosures
1193. Human Transcriptomic Analysis of Periprosthetic Joint Infection
Authors: Masters Thao , Bhagwate Aditya , Dehankar Mrunal , Greenwood-Quaintance Kerryl , Abdel Matthew P , Patel Robin , Patel Robin 
Published: January 2021

Abstract

Background
Periprosthetic joint infection (PJI), a devastating complication of total joint replacement, is of incompletely understood pathogenesis and may sometimes be challenging to clinically distinguish from other causes of arthroplasty failure.

Methods
We characterized human gene expression in 93 specimens derived from surfaces of resected arthroplasties, comparing transcriptomes of subjects with infection- versus non-infection-associated arthroplasty failure.

Results
Differential gene expression analysis confirmed the association of 28 previously investigated biomarkers with PJI- bactericidal/permeability increasing protein (BPI), cathelicidin antimicrobial peptide (CAMP), chemokines CCL3, CCL4, and CXCL2, colony stimulating factor 2 receptor (CSF2RB), colony stimulating factor 3 (CSF3), alpha-defensin (DEFA4), receptor CD64B, intercellular adhesion molecule 1 (ICAM1), IFNG, IL13RA2, IL17D, IL1A, IL1B, IL1RN, IL2RA, IL2RG, IL5RA, IL6, IL8, lipopolysaccharide binding protein (LBP), lipocalin (LCN2), lactate dehydrogenase C (LDHC), lactotransferrin (LTF), matrix metallopeptidase 3 (MMP3), peptidase inhibitor 3 (PI3), and vascular endothelial growth factor A (VEGFA), as well as identified three novel molecules with diagnostic potential for detection of PJI- chemokine CCL20, coagulation factor VII (F7), B cell receptor FCRL4. Comparative analysis of infections caused by staphylococcal versus non-staphylococcal and Staphylococcus aureus versus Staphylococcus epidermidis showed significant elevated expression of IL13, IL17D, and metalloprotease protein MMP3 in staphylocococcal infections, and increased expression of IL1B, IL8, and platelet factor PF4V1 in S. aureus infections. Pathway analysis of over-presented genes suggested activation of host immune response and cellular maintenance and repair functions in response to invasion of infectious agents.

Conclusion
Our study provides new potential targets for diagnosis of PJI and targets for differentiation of PJI-associated infectious agents.

Disclosures
Matthew P. Abdel, MD, Dr. Abdel receives royalties from Stryker on certain hip and knee products, and is a paid consultant for Stryker. (Consultant) Robin Patel, MD, Accelerate Diagnostics (Grant/Research Support)CD Diagnostics (Grant/Research Support)Contrafect (Grant/Research Support)Curetis (Consultant)GenMark Diagnostics (Consultant)Heraeus Medical (Consultant)Hutchison Biofilm Medical Solutions (Grant/Research Support)Merck (Grant/Research Support)Next Gen Diagnostics (Consultant)PathoQuest (Consultant)Qvella (Consultant)Samsung (Other Financial or Material Support, Dr. Patel has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued.)Selux Dx (Consultant)Shionogi (Grant/Research Support)Specific Technologies (Consultant)
1196. Influence of antibiotic use on the effectiveness and safety of immune checkpoint inhibitors in Japan
Authors: Minamishima Takuya , Hida Hirotake , Yamada Kiyofumi 
Published: January 2021

Abstract

Background
It has been reported that antibiotic use changes the gut microbiome and alters the outcome of treatment with immune checkpoint inhibitors (ICIs). However, in Asia, this has not been well studied, and there is insufficient evidence to support these reports.

Methods
In this study, we investigated the concurrent use of antibiotics and the administration of PD-1 inhibitors in Japanese patients, and examined the relationship between antibiotics and the clinical benefit or safety of PD-1 inhibitors.

Results
In total, 152 patients were analyzed: 62 patients received systemic antibiotics within 2 months before or 1 month after the first dose of PD-1 inhibitors (the antibiotic group); the remaining patients comprised the non-antibiotic group. There was a significantly higher proportion of patients under 65 years of age in the antibiotic group. Overall survival (OS) was not reached in the antibiotic and non-antibiotic groups, and there was no statistically significant difference between the two groups (HR = 1.48) (Figure 1). Progression-free survival (PFS) was 3.29 months in the antibiotic group and was significantly shorter than that in the non-antibiotic group (5.99 months, HR = 1.75) (Figure 2). Multivariate analysis by Cox regression analysis also showed that PFS was shorter in the antibiotic group (HR=1.63). As age may be a confounding factor, we performed a stratified analysis, a common method used to adjust for bias. The results of the stratified log-rank test after adjustment for age showed that the PFS was significantly shorter in the antibiotic group. There were no statistically significant differences between the two groups in the response rate, incidence of adverse events of Grade 3 or above, and laboratory data (Table 1).
Figure 1

Figure 2

Table 1

Conclusion
Our results suggest that the use of antibiotics may affect the anticancer treatment outcomes of Japanese patients who are administered PD-1.

Disclosures
All Authors: No reported disclosures
1197. Inhibitory Effect of Ursodeoxycholic Acid on Clostridioides difficile Growth
Authors: Alnezary Faris , Alam M Jahangir , Almutairi Masaad , Fallatah Saad , Begum Khurshida , Gonzales-Luna Anne J , Garey Kevin W 
Published: January 2021

Abstract

Background
Ursodeoxycholic acid (UDCA), a secondary bile acid, inhibits germination and growth of Clostridioides difficile in vitro, but the results from in vivo experiments have been conflicting. We evaluated the effects of UDCA on C. difficile in vitro and in a wax moth, Galleria mellonella model.

Methods
The in vitro growth and germination effects of UDCA on C. difficile were assessed with increased concentration of UDCA (0.001, 0.01, 0.05, and 0.1%). To assess treatment effects of UDCA, C. difficile spores (approximately 1x10^6-8 colony forming units (CFU)) were force fed to G. mellonella larvae treated with UDCA (50 mg/kg/day) 24 hours prior to C. difficile inoculation. Forty G. mellonella larvae were used for each experiment, which was repeated with two distinct strains (R20291 and CD196). Larvae were housed at 37°C and monitored for the next five days for mortality.

Results
In vitro experiment demonstrated inhibition of C. difficile growth at 0.1% concentration (P &lt; 0.001 vs control). Larvae treated with UDCA had a numerically higher survival rate (60% / 24/40) compared to controls (40% / 16/40) but the results were not statistically significant (p=0.14). Identical rates of survival were observed in the control arms for both strains (40%) and similar in the treatment arms (R20291: 70%; CD 196: 50%).

Conclusion
Overall, UDCA shows inhibitory effect of growth and germination of C. difficile in vitro. However, in our G. mellonella model, a single dose of UDCA given prior to infection did not prevent CDI. Further dose dependent, and multiday studies investigating the role of UDCA in CDI is needed to better understand this in vitro / in vivo paradox.

Disclosures
Kevin W. Garey, PharMD, MS, FASHP, Merck & Co. (Grant/Research Support, Scientific Research Study Investigator)