bluuebunny/crossref_metadata_2025_split huggingface dataset:
1317. Porphyromonas gingivalis and Treponema denticola Induce Alzheimer's Disease Biomarkers in Mice
Authors: Butler Catherine A , Mohammed Ali , Paolini Rita , Gomez Stephanie , Toulson Su , Reynolds Eric C , Dashper Stuart G 
Published: November 2023

Abstract

Background
Periodontitis, a chronic disease that progresses over years, is a modifiable risk factor for Alzheimer’s disease (AD). Periodontitis is caused by endogenous oral pathobionts, including Porphyromonas gingivalis (Pg) and Treponema denticola (Td), that have a synergistic relationship resulting in increased virulence. Pg and Td proteins and DNA have been detected in post-mortem brains of AD patients. However it is unclear if these bacteria infect the brain or if the detected bacterial products are on membrane vesicles (MVs); spherical nanostructures released from bacteria. The aims of this work were to determine whether intact bacterial cells were in brains of mice after chronic oral inoculation with these organisms; whether Td enhanced the ability of Pg products to penetrate the brain and whether Td alone induced AD biomarkers

Methods
C57BL/6 mice were orally inoculated 3 times/week for 12 weeks with either Pg, Td, or Pg + Td cells in a 2:1 ratio, or sham inoculated as a negative control. Mice were culled and their brains dissected, with one hemisphere prepared for immunohistochemistry (IHC) as FFPE tissue and probed with antibodies to amyloid beta (Aβ), phospho-Tau (p-Tau) and the Pg surface protein RgpA. The other hemisphere had the hippocampus removed for transmission electron microscopy (TEM) analysis.

Results
Pg alone and Pg + Td inoculated mice showed significant increases in alveolar bone loss compared with the uninoculated control. No whole bacterial cells were detected in any of the brains of inoculated mice including those that were IHC positive for RgpA. RgpA immunoactivity was not significantly different in brains of mice that received Pg alone or the Pg+Td combination. Aβ and p-Tau were detected in all mice with an increasing magnitude in uninoculated &lt; Td inoculated ≤ Pg inoculated ≤ Pg+Td inoculated.

Conclusion
Conclusions: Repeated oral inoculation of mice with Pg alone and Pg + Td resulted in periodontitis, as determined by alveolar bone loss. The lack of whole bacterial cells in the brain argues against a direct infection mechanism of AD initiation by the oral bacteria Pg and Td. Our data are consistent with the observed AD-like pathology in the brain resulting from a focal infection of Pg and/or Td in the mouth mediated by MV penetration of the brain.

Disclosures
All Authors: No reported disclosures
1322. Outcomes Associated with Primary Antibiotic Therapy in Spinal Epidural Abscess due to Staphylococcus aureus: Comparison of First-line vs Alternative Agents
Authors: Fowler Madeline , Phan Jessica , Jaffa Rupal K , Carlson Travis J , Medaris Leigh Ann , Williamson Julie E 
Published: November 2023

Abstract

Background
Spinal epidural abscess (SEA) is an uncommon but serious infection with potentially devastating sequelae. For SEA due to methicillin- susceptible S. aureus (MSSA), anti-Staphylococcal penicillins have been considered first line, however retrospective data have failed to show a difference in outcomes compared to cefazolin. Comparative data in methicillin-resistant S. aureus (MRSA) SEA are sparse.

Methods
This was a multisite, retrospective cohort of adults admitted to an acute care or acute rehabilitation hospital from 1/1/2017 – 9/10/2021 with confirmed S. aureus SEA by radiology and microbiology (blood and/or surgical cultures). Recurrent or polymicrobial SEA, endocarditis, meningitis, or prosthetic joint infection cases were excluded. Therapy was grouped as lower (LCNS) or higher (HCNS) CNS penetration (Fig. 1) and was assessed as overall principal therapy (OPT) (definitive therapy for &gt; 50% of the total course) and early principal therapy (EPT) (definitive therapy for &gt; 50% of the first 2 weeks). Patients were also analyzed by MSSA vs MRSA. The primary outcome was composite 90-day clinical failure, (≥ 1 of the following: extension of original antibiotic course, unplanned surgical intervention related to SEA, recurrence of S. aureus bacteremia, and all-cause mortality) by OPT. Secondary outcomes included components of the primary outcome and composite 90-day clinical failure by methicillin susceptibility and EPT.Figure 1.Lower (LCNS) vs Higher (HCNS) CNS Penetration Agents for Definitive Therapy

Results
174 patients met inclusion: 94 (54%) in the LCNS group and 80 (46%) in the HCNS group. There was no significant difference in 90-day clinical failure of OPT between groups (Fig. 2). The composite 90-day clinical failure of OPT also did not differ between LCNS and HCNS based on methicillin susceptibility (MSSA 25.9% vs. 19.2%, p = 0.49; MRSA 30.8% vs. 31.5%, p = 0.96). Similarly, there was no difference in 90-day clinical failure based on EPT (31% vs. 24%, p = 0.28), regardless of methicillin susceptibility, (MSSA 29% vs. 17.8%, p = 0.18; MRSA 50% vs. 28.8%, p = 0.23) between the LCNS and HCNS groups, respectively (Fig. 3).Table 1.Selected Baseline Characteristics
Figure 2
Figure 3

Conclusion
There was no significant difference in the rate of 90-day composite clinical failure between OPT with LCNS and HCNS. Given the limited sample size, further study, particularly in an MSSA SEA cohort, is warranted.

Disclosures
All Authors: No reported disclosures
1340. Towards better understanding of the epidemiology of SARS-CoV-2 PCR conversion in hospitalized patients: a case-control study
Authors: Manian Farrin A , Karlapalem Chaitanya A 
Published: November 2023

Abstract

Background
The epidemiology of hospitalized patients who "convert" from a negative nasopharyngeal SARS-CoV-2 by PCR to a positive test during the same hospitalization has not been adequately studied.

Methods
This was a retrospective case-control study at 2 large suburban community hospitals. Eligible adult inpatients 18 years or older who underwent 2 or more nasopharyngeal SARS-CoV-2 PCR testing during the same hospital stay from January 1, 2020-March 31, 2021 were included. Controls were randomly selected from a data base of patients with negative repeat test(s) during the same hospitalization at respective hospitals (case-control ratio 1:1)

Results
Of 40 SARS-CoV-2 PCR converters (18 cases from hospital A, 22 cases from hospital B), 23 (57.5%) were 65 years or older, 21 (52%) were female, and 36 (90%) were Caucasian; mean BMI was 28.4. Thirteen (32.5%) patients had 1 or more common Covid-19 symptoms (eg, cough, fever, shortness of breath, weakness, GI symptoms, loss of appetite, confusion) on initial testing (98% within 24 hours of admission). Mean interval between paired tests was 8.4 days; 52.5% were repeated on hospital day 7 or later. Compared to non-converters, converters were less likely to be 65 y or older (58% vs 80%), more likely to be retested due to new Covid-19 symptoms (35% vs 7.5%), had longer hospital stay (17.8 days vs 9.6 days) and had higher in-hospital mortality (32.5% vs zero) (P&lt; 0.001 for all). There was no significant difference between converter and non-converters in the prevalence of Covid-19 symptoms on initial testing, sex, race, BMI, time spent in the ED or other hospital wards, prevalence of selected high-risk Covid-19 comorbidities (eg, hypertension, diabetes, immunocompromised state, COPD, chronic kidney disease or cancer) or interval between paired tests.

Conclusion
Hospitalized patients who convert from a negative to a positive nasopharyngeal SARS-CoV-2 PCR test during the same hospitalization are more likely to be less than 65 y old, be retested because of new-onset Covid-19 symptoms often a week or more days into hospitalization and have significantly longer hospital stay and higher inpatient mortality compared to those of non-converters. More studies are needed to determine factors associated with SARS-Cov-2 PCR conversion in this vulnerable patient population.

Disclosures
All Authors: No reported disclosures
1344. Stakeholders’ Perspectives of the Establishment of SARS-CoV-2 Monoclonal Antibody Infusion Centers in Rural Southwestern Virginia: A Qualitative Analysis with Realist Interview Approach
Authors: Kim Hyun Sue , Baffoe-Bonnie Anthony 
Published: November 2023

Abstract

Background
The COVID-19 pandemic prompted healthcare organizations around the country to rapidly set up infusion centers that were solely dedicated to delivering outpatient COVID-19 monoclonal (mAb) and antiviral infusions. We capture the process of setting up these mAb infusion centers from the perspectives of key stakeholders. These lessons learnt may inform or refine actions in future pandemics.

Methods
A realist interview approach was undertaken to evaluate the effectiveness of the program development with ten key stakeholders and healthcare workers who were involved. In contrast to traditional interviewing methods where a straight question leads to a straight answer, realist interviewing involves capturing the interviewees’ experiences through conversations of teaching and learning. We interviewed ten key stakeholders and healthcare workers who were involved with developing the mAb infusion process from Dec 13th, 2021, to Jan 19th, 2022, over online videoconferencing.

Results
A causal mechanism diagram using a context-mechanism outcome configuration was identified. There was a rapid development of multiple infusion sites over a short time frame with dynamic staffing and patient appointment models leading to rapid increases in mAb infusion capacity in southwestern Virginia.
Figure 1.
Causal mechanism diagram using a CMO configuration for the successful attributes leading to eligible patients treated with monoclonal antibodies.

Conclusion
Strong clinical leadership, a robust communication and feedback framework and shared goals were identified by stakeholders as pivotal in the success of a COVID-19 monoclonal antibody infusion program for a health care system. Pandemic preparedness strategies should hardwire and leverage these features for resiliency.

Disclosures
All Authors: No reported disclosures
1345. Clinical Characteristics and Outcomes of Mild to Moderate COVID-19 Patients with Abnormal Chest Radiologic Findings Treated in the Hospitels in Thailand
Authors: Sayabovorn Naruemit , Phisalprapa Pochamana , Srivanichakorn Weerachai , Chaisathaphol Thanet , Washirasaksiri Chaiwat , Sitasuwan Tullaya , Auesomwang Chonticha , Kositamongkol Chayanis , Nimitpunya Pongpol , Attachitwatin Teerapat , Chayakulkeeree Methee , Phoompoung Pakpoom , Nopmaneejumruslers Cherdchai , Taweemonkongsap Tawatchai , Vamvanij Visit , Tinmanee Rungsima 
Published: November 2023

Abstract

Background
Hospitels are the hotels converted into the healthcare facilities extension in areas with limited resources including hospital beds during the peak of COVID-19 pandemic in Thailand. This study aimed to determine the clinical features and outcomes of asymptomatic and mild to moderate COVID-19 patients who were treated in these facilities.

Methods
We conducted a retrospective study by reviewing the medical records of adult COVID-19 patients who were admitted to Siriraj Hospital’s affiliated hospitels in Bangkok between June and October 2021. Patients’ characteristics, vaccination status, treatment data, and clinical outcomes were collected.

Results
We compared baseline characteristics and clinical features of COVID-19 patients based on their initial chest x-ray (CXR) findings. Of 1,729 patients, 644 (37.2%) had an abnormal baseline CXR, and these patients were older (49.2 vs. 42.2 years, p &lt; 0.001), had higher body weight (68.1 vs. 64.7 kg, p &lt; 0.001) and BMI (26.3 vs. 24.9 kg/m², p &lt; 0.001), and were more likely to have underlying diseases such as diabetes (p = 0.002), hypertension (p &lt; 0.001), obesity (p &lt; 0.001), chronic lung disease (p = 0.029), and autoimmune disease (p = 0.028). They were also more likely to have a risk of disease progression (p &lt; 0.001) and were less likely to be fully vaccinated (p &lt; 0.001). They were more likely to be referred back to the hospital (p &lt; 0.001). We found no significant differences in sex or COVID-19 symptoms between the two groups, except cough and fatigue. The total cost of admission was significantly higher for referred patients than discharged patients (70,545 vs. 12,010 Thai baht, p &lt; 0.001).

Conclusion
A significant proportion of COVID-19 patients with abnormal CXR findings who were admitted to the hospitels had underlying diseases and higher risk of disease progression. Additionally, they were more likely to be referred back to the hospital and had higher healthcare costs. Continued surveillance and monitoring of high-risk COVID-19 patients in hospitels to ensure efficient management and resource utilization were needed.

Disclosures
All Authors: No reported disclosures
1357. Initial and Peak Serum Levels of Krebs von den Lungen-6 for Prediction of Prognosis in Patients with COVID-19
Authors: Kim Geonui , Kwon Hyeonwoo , Ra Sang Hyun , Chang Eui Jin , Bae Seongman , Jung Jiwon , Kim Min Jae , Chong Yong Pil , Lee Sang-Oh , Choi Sang-Ho , Kim Yang Soo , Kim Sung-Han 
Published: November 2023

Abstract

Background
Krebs von den Lungen-6 (KL-6) has been reported to be associated with prognosis in patients with COVID-19. However, there is limited data on the correlation between COVID-19 prognosis and varying KL-6 levels at different time points. We investigated the optimal cutoff values of both initial and peak serum KL-6 levels in order to predict mortality, and also examined their correlation with mortality within 30 days.

Methods
In this retrospective cohort study, data on serially collected serum KL-6 levels in patients hospitalized with COVID-19 between December 2020 and January 2022 at a single tertiary hospital in South Korea were collected. The area under the ROC curve and Youden index were used to determine the cutoff points for the initial and peak KL-6 levels that best predicted 30-day mortality. The association between both initial and peak KL-6 values with 30-day mortality were assessed by univariate and multivariate logistic regression model.

Results
A total of 349 patients were included, and among them, 27 individuals died within 30 days, resulting in a mortality rate of 7.7%. The mean initial and peak KL-6 levels were significantly higher in the non-survivor group compared to the survivor group (898.5 vs. 448.1, p=0.006; 1289.0 vs. 687.3, p=0.003, respectively). The initial and peak KL-6 values that best predicted 30-day mortality were 491.85 U/mL (sensitivity 72.7%, specificity 74.1%, area under curve [AUC] 0.748) and 660.05 U/mL (sensitivity 63.0%, specificity 81.5%, AUC 0.744), respectively. Initial KL-6 greater than 491.85 U/mL (odds ratio [OR], 7.60; 95% CI, 3.10 to 18.59) and a peak KL-6 greater than 660.05 U/mL (OR 7.55; 95% CI 2.56 to 22.26) were found to be significantly associated with 30-day mortality, independent of age, solid cancer, and elevated serum C-reactive protein ( &gt; 7.5 mg/dL).

Conclusion
We found that both initial and peak levels of KL-6 were significantly related to 30-day mortality in hospitalized COVID-19 patients. These findings suggest that serially monitoring blood KL-6 levels could serve as a valuable prognostic indicator for COVID-19.

Disclosures
All Authors: No reported disclosures
1363. Preliminary Safety Results from a Phase 1 First in Human Study of VYD222: an Extended Half-Life Monoclonal Antibody (mAb) in Development for COVID-19 Prevention
Authors: Mahoney Kathryn , Gupta Deepali , Li Yong , Betancourt Natalia , Das Aanika , Campanaro Ed , Schmidt Pete 
Published: November 2023

Abstract

Background
VYD222 is a fully human IgG1 mAb demonstrating broad and potent in vitro neutralizing activity across SARS-CoV-2 variants including XBB.1.5. VYD222 is a re-engineered version of adintrevimab, an Fc-modified mAb that has a robust safety data package and demonstrated clinically meaningful results in Phase 2/3 clinical trials for both treatment and prevention of COVID-19 (NCT04805671, NCT04859517). VYD222 is currently in development for COVID-19 prevention.

Methods
This is an ongoing Phase 1, first in human, blinded, randomized, placebo (PBO)-controlled, single ascending dose study of VYD222 administered as slow intravenous (IV) push to healthy adults aged 18-65 years (NCT05791318). Participants were randomized 8:2 in each of 3 cohorts (n=8 VYD222, n=2 PBO): VYD222 1500 mg, 2500 mg, and 4500 mg. Safety and tolerability will be assessed as incidence of treatment emergent adverse events, including serious adverse events (SAEs). Serum pharmacokinetic (PK) parameters will be calculated for VYD222 using noncompartmental analysis methods. Serum virus neutralizing antibody (sVNA) titers of VYD222 ex vivo against relevant SARS-CoV-2 variants will be assessed using a validated assay. Safety, tolerability, PK, and sVNA titers will be assessed through 12 months post-dose. Here we report preliminary blinded safety results from cohorts 1 and 2.

Results
Overall, 12 participants received VYD222 or PBO. Through a minimum of 14 days post dose, among 10 participants in cohort 1 (VYD222 1500 mg n=8, PBO n=2), there were 9 AEs (adverse events) reported, all of which were mild in severity and considered unrelated to study drug. No participant experienced SAEs, infusion-related reactions, or hypersensitivity reactions. Through 2 days post dose, 2 sentinel participants in cohort 2 (VYD222 2500 mg n=1, PBO n=1) experienced zero AEs, study drug related AEs, SAEs, infusion-related reactions, or hypersensitivity reactions. Enrollment continues in cohort 2 as of the data cutoff (04/25/2023) for this abstract. Data remain blinded currently.

Conclusion
To date, a single dose of VYD222, up to 2500 mg IV push, was well tolerated across all healthy participants receiving either VYD222 or PBO in this ongoing phase 1 study. These findings support continued clinical development of VYD222.

Disclosures
Kathryn Mahoney, PharmD, Invivyd, Inc.: Employee|Invivyd, Inc.: Stocks/Bonds Deepali Gupta, BSc, Invivyd, Inc.: Employee|Invivyd, Inc.: Stocks/Bonds Yong Li, PhD, Invivyd, Inc.: Employee|Invivyd, Inc.: Stocks/Bonds Natalia Betancourt, MS, Invivyd, Inc.: Employee|Invivyd, Inc.: Stocks/Bonds Aanika Das, PharmD, Invivyd, Inc.: Employee|Invivyd, Inc.: Stocks/Bonds Ed Campanaro, MS, Invivyd, Inc.: Employee|Invivyd, Inc.: Stocks/Bonds Pete Schmidt, MD, Invivyd, Inc.: Employee|Invivyd, Inc.: Stocks/Bonds
1377. Rabies and Tetanus Post-Exposure Prophylaxis Initiation in the US and Overseas: Consistent with ACIP Recommendations?
Authors: Chirumamilla Siri L , Breiman Jennifer , Fairley Jessica K , Wagonner Jesse J , Collins Matthew H , Wu Henry M 
Published: November 2023

Abstract

Background
Appropriate management of animal bites is critical to prevent rabies encephalitis and tetanus. In the US, rabies post-exposure prophylaxis (PEP) is typically started in emergency departments (EDs). For travelers seeking care overseas, World Health Organization (WHO) PEP guidance differs from those of the Advisory Council on Immunization Practices (ACIP). WHO does not recommend rabies immune globulin (RIG) for minor scratches; furthermore, RIG availability can vary worldwide. Outpatient follow-up of patients not given RIG is challenging because RIG is often not given in clinics. We assessed whether patients referred to a travel medicine clinic for rabies PEP vaccination were initially managed in accordance with ACIP guidance.

Methods
Medical records of patients presenting for rabies PEP at the Emory TravelWell Center from 2017-21 were reviewed. Initial management after exposure at the patient’s first healthcare interaction was assessed for consistency with ACIP recommendations for rabies and tetanus PEP.

Results
Fifty-six patients were seen for rabies PEP from 2017-21. The median age was 38 years (range 5 to 67). Most patients were exposed in the US (71%). Animal bites accounted for most exposures (57%), followed by suspected contact without visible bite or scratch (38%), and scratches (5%). Frequently involved animals were bats (41%), dogs (30%), cats (14%), and monkeys (7%). A tetanus booster was indicated but not given in 59% of patients. Most patients (82%) received ACIP-consistent rabies PEP. Among the 10 patients who did not, seven (70%) had initiated PEP overseas without RIG. Three patients who initiated PEP in the US received PEP that was inconsistent with ACIP guidance; two did not receive RIG and one received gluteal vaccination. None developed symptomatic rabies or tetanus infection.

Conclusion
Patients seen at a travel clinic for rabies PEP often start it elsewhere, and in this series 18% of patients had PEP initiation inconsistent with ACIP guidance. Returned travelers who initiated PEP in accordance with WHO guidance account for most situations where RIG was not given. Errors in rabies and tetanus PEP also occurred in US EDs. US providers administering rabies and tetanus PEP should ensure practices adhere to ACIP guidance.

Disclosures
All Authors: No reported disclosures
1399. Pancreatic Abscess in Disseminated Melioidosis
Authors: Saw Yen Tsen , Lee Heng Gee , Yong Kylie Sze Tyng , Kok Suet Hwa 
Published: November 2023

Abstract

Background
Melioidosis is an infection caused by the gram-negative bacterium Burkholderia pseudomallei that is widely distributed in the tropical regions of Southeast Asia. It is commonly associated with intraabdominal abscesses, particularly the liver and spleen. However, there is scarce literature regarding pancreatic involvement in melioidosis. We describe a case series of pancreatic manifestations of disseminated melioidosis in a tertiary hospital in Sabah, Malaysia.

Methods
We conducted a retrospective case review of 63 patients with culture-positive melioidosis admitted in Queen Elizabeth Hospital, Sabah between December 2021 and March 2023 and identified cases with pancreatic involvement diagnosed by radiological imaging.

Results
Pancreatic involvement was reported in 3 patients (4.8%). Median duration of symptoms was 20 days. All three patients had risk factors for melioidosis (3 had poorly controlled diabetes mellitus and 1 had chronic kidney disease), and had infection involving other organs (lungs, liver, spleen and prostate). Pancreatic lesions were all detected by computed tomography scans in the tail region and ranged from small microabscesses to large solitary lesions (largest dimension 5.6 cm) with peripancreatic fat stranding. One patient required emergency hemodialysis and intensive care. Drainage of concurrent prostatic abscess was done for one patient. All 3 patients were treated with antibiotics alone (median 38 days of intensive therapy) without drainage of pancreatic abscess and showed regression of pancreatic lesions upon reassessment imaging.

Patient demographic and disease details. DM, diabetes mellitus; CKD, chronic kidney disease; CT, computed tomography.
Figure 1
(A) Contrast-enhanced computed tomography image showing a heterogenous hypodense lesion at the pancreatic tail (arrow) and multiple ill-defined splenic lesions (arrowhead). (B) Smaller lesions at the pancreatic tail and spleen after 35 days of antibiotics (Case 1).

Conclusion
Surgical drainage is required for source control of large melioidotic abscesses, however it may not be feasible for smaller pancreatic abscesses which are often multifocal and deep seated. In our study, the patients with pancreatic abscesses showed good clinical improvement with antibiotics therapy without drainage. Further studies are needed on the role of debridement for pancreatic melioidosis. Published guidelines recommend treatment of melioidosis with deep-seated abscesses with four weeks of intravenous ceftazidime as intensive therapy, followed by three to six months of oral trimethoprim-sulfamethoxazole or doxycycline as eradication therapy.

Disclosures
All Authors: No reported disclosures