bluuebunny/crossref_metadata_2025_split huggingface dataset:
2115. Long Term Follow-up and Correlates of Success in Patients on Immune Globulin for Antibody Deficiency
Authors: Duffield Olivia , Axelrod Peter 
Published: December 2022

Abstract

Background
Antibody deficiencies range from mild deficits of antibody subclasses to more severe deficiencies of all immune globulins. Patients with deficiencies of immune globulin G (IgG) are predisposed to recurrent sinopulmonary infections, often necessitating multiple courses of antibiotics and frequent hospitalizations and provider visits. Treatment with intravenous immune globulin (IVIG) replacement therapy is currently indicated for patients with severe primary immune deficiencies but is less well studied in patients with more mild deficits that nonetheless experience recurrent infections.

Methods
A retrospective chart review was conducted on 71 patients from the Temple University Infectious Disease Department (15 transplant recipients) with varying levels of antibody deficiency that had been treated with monthly IVIG for at least six months. Available patients (N=49) were interviewed by phone about their experiences on IVIG, side effects, and quality of life changes on therapy.

Results
Mean age sx onset was 40 y,68% were women, 87% Caucasian, 49% had pneumonia, 65% purulent bronchitis, 65% sinusitis. Patients reported a mean reduction in infection frequency of 78% and average patient-reported improvement in quality of life was 4.7/5.0. Antibody deficiency levels at baseline were not correlated with infection reduction (R=-.05, p=0.71), Figure 1 and neither was response to pneumococcal polysaccharide vaccine (vaccine responder median infection reduction 83%; non responder 87%, p= 0.60) Figure 2. Adverse events on treatment were experienced by 59% of patients and caused 9 patients (13%) to stop treatment. There was no difference in incidence of adverse events between men and women (p= 0.076), but women had a 50% higher rates of severe headache than men (p= 0.038); 10% pts required a port or PICC, 32% IV fluids, 48% IV steroids, 31% IVIG brand change; 17% changed to subcutaneous IG. Figure 1:Pre-treatment Antibody Deficit and Infection Reduction by IVIGPlot of percent deficit of most deficient antibody subclass against infection reduction by IVIG (% of yearly pre-IVIG infections)Infection Reduction by IVIG According to Vaccine Responsiveness
Box plot of percent infection reduction after IVIG according to response to polysaccharide vaccine

Conclusion
Even patients with relatively mild immunoglobulin deficiencies can experience a significant reduction in recurrent infections and improved quality of life when treated with immunoglobulin. IVIG is usually well tolerated for many years but may require adjunctive steroids, IV hydration, or brand change to limit adverse side effects.

Disclosures
All Authors: No reported disclosures.
2123. The Impact of Staphylococcus aureus Peri-transplant Cultures on Six-Month Outcomes in Lung Transplantation
Authors: Harris Courtney E , Mehta Abhinav , Kim Andy J , Goldberg Hilary J , Mallidi Hari R , Mallidi Hari R , Townsend Keri , Coppolino Antonio , Thaniyavarn Tany , Kennedy John C , Lee Stefi F , Durney Valerie , Marshall Shirley , Fenty-Scotland Jessica , Cosimi Lisa A , Kovac Victor , Issa Nicolas C , Sharma Nirmal S , Baden Lindsey R , Woolley Ann E 
Published: December 2022

Abstract

Background
Staphylococcus aureus (S. aureus) infections post-lung transplant lead to increased mortality. The impact of S. aureus peri-transplant respiratory cultures on post-transplant outcomes is unknown as is the optimal duration of peri-transplant antibiotics. We compared lung transplant recipients with and without S. aureus growth on peri-transplant cultures and the impact on 6-month outcomes including rejection, survival, and occurrence of S. aureus infections.

Methods
A single-center, retrospective study of lung transplant recipients between January 2017 and April 2021 was performed. Donor/recipient characteristics, microbiologic data, antibiotics, and 6-month outcomes were analyzed.

Results
In this 4.5-year study period, 229 patients underwent lung transplant. 121 (53%) had S. aureus growth on peri-transplant cultures, of which 84 (69%) were methicillin-susceptible (MSSA), 30 (25%) methicillin-resistant (MRSA), and 7 (6%) had MSSA and MRSA. Median duration of antibiotics post-transplant was 28-days in the S. aureus group. 67% of non-S. aureus recipients received S. aureus targeting antibiotics (p = &lt; 0.001) for other indications for a median of 13-days. In the S. aureus cohort, donors were younger (median age 33 vs 38 years, p = 0.027) and more donors died from drug intoxication (50% vs 31%, p = 0.005) [Table 1]. Recipient baseline characteristics and median length of hospitalization were similar in both cohorts. There were no statistically significant differences in 6-month outcomes, including rates of rejection or survival [Figure 1]. Having grown S. aureus in peri-transplant cultures was not associated with a higher incidence of post-transplant S. aureus infections (10% vs 13%, p = 0.534). Patients who had a S. aureus infection post-transplant had lower 6-month survival that was not statistically significant (85% vs 93%, p = 0.131).

Conclusion
The growth of S. aureus on peri-transplant respiratory cultures with a median 4-week antibiotic course does not increase the risk of having a S. aureus infection post-transplant and is not associated with increased mortality or rejection at 6-months. The impact of a shorter duration of peri-transplant antibiotics on recurrence of infection and outcomes needs to be further studied.

Disclosures
Nicolas C. Issa, MD, AiCuris: Grant/Research Support|Merck: Grant/Research Support.
2141. Investigating a (Natural) Killer by Studying the Victims: Searching for Mechanisms to Selectively Inhibit NK-cell Immunosuppressive Function to Improve Vaccine Responses
Authors: Cox Andrew , Waggoner Stephen N , Katko Alexander , Roskin Krishna 
Published: December 2022

Abstract

Background
Decades of effort have yet to deliver an efficacious vaccine for pathogens such as HIV, despite major revelations about HIV antigens and development of new vaccine platforms. Innovative outside-the-box approaches are needed to overcome immunological roadblocks to the success of past and current vaccine regimens. We discovered that natural killer (NK) cells are a potent obstacle to vaccine success through perforin-dependent suppression of activated CD4 T cell responses early after vaccination. This killing reduces the quantity and quality of antibody responses. Yet, the features of NK cells that enable this activity or determine susceptibility of specific subsets of T cells remain ill-defined.

Methods
We used transgenic virus-specific mouse CD4 T cells to detect very early changes in responding T cells immediately proximal to immunoregulatory killing by NK cells. Transgenic T cells were seeded in recipient mice, depleted or not of NK cells, and then infected with lymphocytic choriomeningitis virus. At early time points post-infection, these T cells were isolated for single-cell RNA-sequencing or high-dimensional flow cytometry analyses. These data revealed transcriptomic and proteomic features of subsets of activated CD4 T cells whose presence was enabled or enhanced by the absence of NK cells.

Results
Perforin-dependent killing of CD4 T cells by NK cells is measurable on days 2 and 3 post-infection. Analysis of the pool of responding T cells on day 3 revealed phenotypic skewing away from follicular helper T cell-type responses to Th1-type responses in the presence of NK cells. Single cell RNA sequencing and high-dimensional spectral flow cytometry reveal clusters of T cells that are markedly enriched in the absence of NK cells.

Conclusion
We created a model system permitting characterization of the population of T cells targeted by NK cells after infection or immunization. Elucidation of features of the targeted T cells will provide mechanistic insights in the receptor-ligand system enabling this biology, improve our understanding of how NK cells influence the pool of responding T cells, and facilitate discovery of the corresponding subset of NK cells responsible for this activity. These discoveries are likely to facilitate development of methods to enhance vaccine responses.

Disclosures
All Authors: No reported disclosures.
2162. Risk Factors Associated with Hospitalization among 0 to 21 Years Old Patients with Active Asthma/Active Airway Disease: Preliminary Findings from Multi-Center Study Across United States.
Authors: Pardasani Sapna , Dallas Ronald H , Ross Hailey S , Ferrolino Jose A , Fisher Brian T , Danziger-Isakov Lara A , Muller William J , Maron Gabriella , Kitt Eimear 
Published: December 2022

Abstract

Background
More data are needed to understand the risk for COVID-19 severity among pediatric asthma patients. We present findings from a national registry characterizing COVID-19 hospitalizations among pediatric asthma patients.

Methods
Data were obtained from the Pediatric COVID-19 US Registry, which included medical records of COVID-19 cases &lt; 21 years old between March 2020 and May 2021. Those with asthma were eligible while immunocompromised and transplant cases were excluded. Descriptive statistics and chi-square tests were performed.

Results
Of the 1089 eligible asthma cases, half were 12 to 17 years old [Figure 1], the majority were male [Figure 2], a third Black African American [Figure 3], and most were Non-Hispanic/Latino 825 (76%). 242 (22%) reported a history of smoking.
A fourth of cases (257 (23.6%) were hospitalized for COVID-19. More than half (54%) reported asthma as their only pre-existing condition. The majority (n=71, 28%) were taking regular inhaled corticosteroids. Almost half (n=120, 47%) had abnormal chest radiographic findings, 20 (7.8%) had abnormal CT findings, and 24 (9%) progressed to lower respiratory infection. About 10% (n=25) needed mechanical ventilation. A third (n=88, 34%) required ICU care with 33% of those receiving inhaled corticosteroids. A quarter needed mechanical ventilation [Figure 5].
Compared to asthma patients not hospitalized for COVID-19, those hospitalized were significantly (P&lt; 0.05) more likely to be non-Hispanic, havemultiple pre-existing conditions, and be obese [Figure 6]. Compared to those not admitted to ICU, ICU cases were significantly more likely to be obeseand be diagnosed with MIS-C [Figure 7].
Demographics
The majority of cases (N=479, 44%) were between 12 and 17 years old, Male (N=610,56%) and Black or African American (N=410, 38%).
Clinical Characteristics
Risk factors assessment

Conclusion
This is one of the first national studies examining COVID-19 among pediatric cases with asthma. Our data suggest that children with asthma who have multiple pre-existing conditions and/or are obese have a higher risk for hospitalization. These early data may aid clinicians in developing future prospective studies to understand COVID-19 risk among this vulnerable population.

Disclosures
Lara A. Danziger-Isakov, MD, Ansun BioPharma: Contracted clinical research|Astellas: Contracted clinical research|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Contracted clinical research|Pfizer: Contracted clinical research|Takeda: Grant/Research Support|Takeda: Contracted clinical research|Viracor: Grant/Research Support.
2190. Characterization of Inhaled Nitric Oxide (iNO) for the treatment of Viral Community Acquired Pneumonia (CAP)
Authors: Tal Asher , Shifer Yehonatan , Wolak Talya , Grossman Alon , Dicker Dror 
Published: December 2022

Abstract

Background
Nitric Oxide (NO) has been previously demonstrated to have antimicrobial, anti-inflammatory, and vasodilator properties. Extensive work has been done in the clinical setting to explore these properties with iNO administered intermittently at high concentrations of 150-250 ppm. While viral CAP has gained major attention with the emergence of COVID-19, treatment methods remain limited and are challenging to develop. The purpose of this study is to assess iNO treatment administered to hospitalized adults with viral CAP.

Methods
This is a randomized, open label multi-center ongoing study. Study population includes subjects aged 18-80, hospitalized for vCAP including COVID-19. Following enrollment, subjects were randomized 1:1 to either iNO [150ppm for 40 minutes, 4 times daily, up to 7 days in addition to standard supportive treatment (SST)], or control [SST alone]. iNO was delivered by LungFitTM, an innovative NO generator under development (Beyond Air, NY, USA). Follow up period is 180 days. Study endpoints include safety and the time to reach a stable saturation of ≥93%. In addition, different other clinical parameters are collected to profile the effect of iNO in this population.

Results
Analyzing the Intent To Treat (ITT) population (n=35, [16 iNO and 19 control]), safety profile of iNO treatment observed so far, was found to be favorable with no treatment related Adverse Events (AEs). Faster clinical improvement was noted in the iNO treatment group, paralleling CRP improvement between baseline to end of treatment (mean 2.7 mg/dl comparing treatment group [n=8] to control group [n=7], data not final).

Conclusion
These data suggest that intermittent treatment with 150ppm iNO is safe and well tolerated and may contribute to faster clinical improvement in viral CAP. Different laboratory parameters may shed some light and help to characterize this observed effect, supporting the further exploration of iNO for the treatment of viral lower respiratory tract infection, including COVID-19.
Preliminary findings were presented at ECCMID 2022

Disclosures
Asher Tal, MD, Beyond Air Inc: Advisor/Consultant|Beyond Air Inc: Stocks/Bonds Talya Wolak, MD, talya wolak: Advisor/Consultant Dror Dicker, MD, AstraZenca: Advisor/Consultant|AstraZenca: Honoraria|Beyond Air: Grant/Research Support|Boehringer Ingelheim: Advisor/Consultant|Boehringer Ingelheim: Honoraria|Eli Lilly: Grant/Research Support|Novo Nordisk: Advisor/Consultant|Novo Nordisk: Grant/Research Support|Novo Nordisk: Honoraria.
2208. Rates of Medically-Attended RSV among US Adults: A Systematic Review and Meta-Analysis
Authors: McLaughlin John M , Khan Farid L , Begier Elizabeth , Swerdlow David , Jodar Luis , Falsey Ann R 
Published: December 2022

Abstract

Background
Adult respiratory syncytial virus (RSV) vaccines are in late stages of development. A comprehensive synthesis of adult RSV burden is needed to inform public health decision-making.

Methods
We performed a systematic review and meta-analysis of studies describing the incidence of medically-attended RSV (MA-RSV) among US adults. We also identified studies reporting nasopharyngeal (NP) or nasal swab RT-PCR results with paired serology (four-fold-rise) or sputum (RT-PCR) to calculate RSV detection ratios quantifying improved diagnostic yield after adding a second specimen type (ie, serology or sputum).

Results
We identified 14 studies with 15 unique MA-RSV incidence estimates, all based on NP or nasal swab RT-PCR testing alone. Pooled annual RSV-associated incidence per 100,000 adults ≥65 years of age was 178 (95%CI: 152‒204; n=8 estimates) hospitalizations (4 prospective studies: 189; 4 model-based studies: 157), 133 (95%CI: 0‒319, n=2) emergency department (ED) admissions, and 1519 (95%CI: 1109‒1929, n=3) outpatient visits. Based on 6 studies, RSV detection was ∼1.5 times higher when adding paired serology or sputum. After adjustment for this increased yield, annual RSV-associated rates per 100,000 adults ≥65 years were 267 hospitalizations (UI: 228‒306) (prospective: 282; model-based: 236), 200 ED admissions (UI: 0‒478), and 2278 outpatient visits (UI: 1663‒2893). Persons &lt; 65 years with chronic medical conditions were 1.2−28 times more likely to be hospitalized for RSV depending on risk condition.

Conclusion
The true burden of RSV has been underestimated and is significant among older adults and individuals with chronic medical conditions. A highly effective adult RSV vaccine would have substantial public-health impact.

Disclosures
John M. McLaughlin, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Farid L. Khan, MPH, Pfizer: Employee|Pfizer: Stocks/Bonds Elizabeth Begier, M.D., M.P.H., Pfizer: Employee|Pfizer: Stocks/Bonds David Swerdlow, MD, Pfizer: Advisor/Consultant|Pfizer: Stocks/Bonds Luis Jodar, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Ann R. Falsey, MD, BioFire Diagnostics: Grant/Research Support|Janssen: Grant/Research Support|Merck, Sharp and Dohme: Grant/Research Support|Novavax: Advisor/Consultant|Pfizer: Grant/Research Support.
2216. ROAR ED-SANE: A Retrospective Observational Assessment Review of an Emergency Department Sexual Assault Nurse Examiner Program’s Adherence to CDC Guidelines for Sexually Transmitted Infections
Authors: Nelson Jennifer , Woolever Nathan L , Meyer Lisa M , Hall Scott T , Stakston Jaclyn , Dababneh Ala , Van Sistine Michael , Tempelis Jennifer M , Dierkhising Ross , Lessard Sarah R , Roush Kathleen 
Published: December 2022

Abstract

Background
Sexual assault survivors are at increased risk for sexually transmitted infections. Due to patient vulnerability, institutions have implemented Sexual Assault Nurse Examiner (SANE) protocols to care for these patients. These protocols guide evidence collection, testing, treatment, and medical follow-up to ensure optimization of sexually transmitted infections (STIs) treatment, monitoring and follow-up. Previous gap analyses have identified decreased prescribing of prophylactic STI medications and scheduling follow-up appointments compared to guideline recommendations. The purpose of this study was to assess adherence of medication prescribing and follow-up scheduling practices to Centers for Disease Control (CDC) guidelines.

Methods
This study was a single-center, retrospective, observational, descriptive assessment which evaluated adherence rates to CDC guidelines, to scheduling medical follow-up, and patient attendance at scheduled appointments. Pediatric and adult patients who presented to the emergency department at Mayo Clinic Health System in La Crosse, WI from January 2018 through December 2021 were included. Data collected through chart review included demographics and laboratory data necessary for prescribing prophylactic HIV medications, antibiotics for STIs, emergency contraception, and vaccine administration. Descriptive statistics were used to evaluate results.

Results
One hundred three patients were evaluated. Majority of patients were female and presented within 3 days of assault. Medication adherence to CDC guidelines was ≥ 80% for chlamydia and gonorrhea whereas &lt; 80% was noted for trichomoniasis and HIV prophylaxis. Adherence to post-ED discharge follow-up was 40%.

Conclusion
Opportunities to improve adherence of ED-SANE protocols for medication prescribing and medical follow-up for trichomoniasis and HIV prophylaxis exist.

Disclosures
All Authors: No reported disclosures.
LB746. Safety and Immunogenicity of a Booster Dose of Novavax COVID-19 Vaccine, Adjuvanted (NVX-CoV2373) in Adults from the PREVENT-19 Trial in the United States
Authors: Áñez Germán , Dunkle Lisa M , Gay Cynthia L , Kotloff Karen L , Patel Nita , Plested Joyce S , McGarry Alice , Woo Wayne , Cai Rongman , Cho Iksung 
Published: December 2022

Abstract

Background
Novavax COVID-19 Vaccine, Adjuvanted (5 µg recombinant spike protein/50 µg Matrix-MTM adjuvant; NVX-CoV2373) has received regulatory authorizations for use in adults ≥ 18 years globally.

Methods
Participants from PREVENT-19 (NCT04611802), a phase 3, randomized, observer-blinded, placebo-controlled trial that evaluated the efficacy, safety, and immunogenicity of a primary series of 2 doses of NVX-CoV2373 given 21 days apart, in adults ≥ 18 years in the United States and Mexico, were eligible to receive a booster dose at least 6 months after the initial vaccination series. Short-term safety and immunogenicity of the booster dose was assessed in an ad hoc analysis of 298 participants.

Results
There was an incremental increase compared to the initial vaccination series in local and systemic reactogenicity, which was transient and mostly mild-to-moderate in intensity. Most unsolicited adverse events were also mild-to-moderate in severity; there were no deaths or treatment-related SAEs and 2/298 booster recipients in this analysis reported unrelated SAEs. Neutralizing, anti-S IgG, and hACE2 receptor binding inhibiting antibodies against the ancestral (Wuhan) strain 28 days after booster were higher than those 14 days after primary vaccination (Table). Overall, humoral responses were high regardless of interval between priming and booster vaccination, but a longer interval yielded stronger responses. Higher immune responses against the Omicron BA.1, BA.2, and BA.5 variants were also observed after the booster dose than after the primary series in a subset of 14-18 participants tested. Overall, humoral responses were high and broad regardless of age after any vaccination, but higher responses were observed in adults &lt; 65 years after initial and booster vaccinations. A booster dose induced more robust antibody responses compared with the primary series in adults ≥ 65 years.

Conclusion
A single booster dose of NVX-CoV2373 demonstrated a satisfactory safety profile, and high levels of neutralizing, anti-S IgG, and hACE2 inhibition antibody responses against the SARS-CoV-2 prototype Wuhan as well as against the Omicron variant including recently emerged sub-variants.

Disclosures
Germán Áñez, MD, Novavax Inc.: employer|Novavax Inc.: Stocks/Bonds Lisa M. Dunkle, MD, Novavax, Inc: Employee|Novavax, Inc: Stocks/Bonds Nita Patel, MS, CRP, Novavax, Inc.: employer|Novavax, Inc.: Stocks/Bonds Joyce S. Plested, PhD, Novavax Inc.: employer|Novavax Inc.: Stocks/Bonds|Novavax Inc.: Stocks/Bonds Alice McGarry, MPH, Novavax: Employee|Novavax: Stocks/Bonds Wayne Woo, MS, Novavax: Employee|Novavax: Stocks/Bonds Rongman Cai, PhD, Novavax Inc.: employer|Novavax Inc.: Stocks/Bonds Iksung Cho, MS, Novavax, Inc.: employer|Novavax, Inc.: Stocks/Bonds.