bluuebunny/crossref_metadata_2025 huggingface dataset:
858. Diagnostic Accuracy of Monocyte Distribution Width as a Sepsis Biomarker in a Large, Urban Emergency Department
Authors: Crew Jordan , Hunter Ben , Desai Armisha
Published: November 2023

Background

Sepsis is a leading cause of hospital and emergency department (ED) mortality, and early identification is crucial. Procalcitonin (PCT), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) are increasingly being utilized to aid in the early identification of septic patients. Recently, monocyte distribution width (MDW), a measure of the range in size of monocytes in the blood, has shown promise as an additional sepsis biomarker; levels > 20 have been correlated with an increased risk of sepsis. This investigation sought to determine the diagnostic accuracy of MDW as a marker of sepsis, and compare the accuracy to that of PCT, CRP, and ESR.

Methods

This is a retrospective chart review of adult ED patients from 4/1/2022 to 7/31/2022 in whom an MDW was resulted. During this time, MDW was included as part of all CBC reports. We collected PCT, CRP, and ESR results if obtained within 48 hours of the MDW. Sepsis diagnoses were based on a primary ICD-10 diagnosis of sepsis (A40-A41) at ED or hospital discharge. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for MDW in all patients, MDW only in patients with PCT also ordered (regardless of PCT result), PCT, CRP+ESR, and MDW+PCT for the sake of comparison. MDW was considered “positive” for sepsis if > 20.

Results

There were 10,654 patient encounters with MDW reported. The mean age was 51 years old, and 55% of patients were female. Of the 10,654 encounters, 269 (2.5%) had a sepsis diagnosis on discharge. Diagnostic test results for MDW, PCT, and ESR and CRP are displayed in Table 1. Among all ED patients with a CBC, MDW had a sensitivity, specificity, PPV, and NPV of 82%, 69%, 6.7% and 99%, respectively. In 847 patients where infection was being considered (based on the independent ordering of PCT), MDW sensitivity, specificity, PPV, and NPV were 85%, 53%, 29% and 94%, respectively. MDW was more sensitive but less specific than PCT. In cases of both positive MDW and PCT, the PPV for sepsis was 43%.

Conclusion

These findings suggest that, as a marker for sepsis, MDW has comparable test characteristics to ESR and CRP, with higher sensitivity but lower specificity than PCT. The combination of a positive MDW and PCT was most predictive of sepsis.

Disclosures

Ben Hunter, MD, Beckman Coulter: Honoraria
863. ELISpot-BK virus assay for the assesment of BK virus cell-mediated immunity in kidney recipients
Authors: Herrera Sabina , Sempere Abiu , Egri Natalia , Maurandi Javier Bernal , Cofan Frederic , Marcos María Angeles , Pascal Mariona , Bodro Marta
Published: November 2023

Background

The pre and post-transplant monitoring of BKV-specific T cells could be a useful marker to identify renal receptors at risk of BKV reactivation and consequently develop BKV nephropathy.

Methods

We performed a prospective multicenter study between October 2020 and December 2021. BKV-ELISPOT was performed before and two months after kidney transplantation in included patients. Other variables such as demographic, immunosuppressive therapy, presence of biopsy-proven rejection, lymphopenia, CD4 count levels and development of BK infection and nephropathy were prospectively recorded.

Results

We included 66 patients during the study period of whom median age was 56 (SD 16) and 60% were men. Twenty-nine percent of them received a prior transplantation, 17% was a living donor and 74% needed haemodialysis prior transplantation. Ninety-two percent received induction therapy and 86% maintenance therapy was with 3 drugs. Fifty-one percent of patients presented lymphopenia at 2 months post transplantation with a median CD4 count levels of 298 (IQR 176-899). Prior transplantation 30% of patients presented a reactive ELISPOT-BKV test, whereas at 2 months post transplantation only 21% of them tested positive. Five patients presented a BK infection and 2 of them a BK nephropathy, all of them presenting with impaired graft function at one year post transplantation.Twenty-eight percent of them presented a biopsy-proven acute rejection. All patients that presented a BKV infection presented a non-reactive ELISPOT-BKV test prior transplantation and at 2 months post transplantation. After performing multivariate analysis, neither lymphopenia, acute allograft rejection nor ELISPOT-BKV test were related to BKV infection, probably due to low incidence of BKV infection in this subgroup of kidney recipients.

Conclusion

BKV-ELISPOT test could be a valuable tool to predict BKV infection or nephropathy and could be useful to implement preventive measures such pre-emptive reduction of immunosuppressive therapy in kidney recipients.

Disclosures

All Authors: No reported disclosures
872. Characterizing Plasma Microbial Cell-Free DNA Sequencing Detections of Public Health Important Pathogens
Authors: Park Sarah Y , Chang Eliza J , Lau Constance , Berman David , Nolte Frederick S
Published: November 2023

Background

Timely pathogen identification is critical for meaningful disease surveillance to facilitate effective public health responses. However, public health important pathogens are often diagnostically challenging (e.g., indeterminate serological results, multiple samples separated by long intervals, lengthy turnaround times) and at odds with public health needs. We describe detections of public health important pathogens by the Karius Test®, a validated plasma microbial cell-free DNA (mcfDNA) sequencing test, providing real-time pathogen detection.

Methods

We identified nationally notifiable infectious diseases (NNID)-associated and selected state reportable pathogens detected and quantified as DNA molecules/μl (MPM) in US patients’ plasma samples submitted to the Karius CLIA certified/CAP accredited laboratory for mcfDNA sequencing between 4/1/18–4/30/22. We evaluated and characterized these detections based on result and test requisition form data. We reviewed gender and immunocompromised status of a subset of patients linked deterministically to the Premier Healthcare Database (PHD), a US hospital-based, all-payer database.

Results

Plasma mcfDNA sequencing yielded 520 detections of 62 microbes associated with 27 NNIDs and 449 detections of an additional 12 microbes, including public health important parasites, amoebae, endemic mycoses, and selected bacteria, across 27 US states. MPM and patient age varied widely across microbes from 9–300+ million and 0–89 years, respectively (Table 1). For the 167 (17%) PHD-linked detections, 71% were associated with male and 72% with immunocompromised patients.

Conclusion

Plasma mcfDNA sequencing detected many different public health important pathogens across many states, especially among immunocompromised patients. These patients pose a heightened public health concern given their increased risk for more severe disease and potential for longer infectious periods and greater likelihood of atypical or nonspecific presentations, leading to greater risk of unrecognized disease spread. Plasma mcfDNA sequencing, an unbiased test, may contribute to rapidly identifying disease outbreaks and spread, and facilitate timely interventions to improve public health.

Disclosures

Constance Lau, MPH, Karius, Inc.: Stocks/Bonds David Berman, DO, Precision Health Solutions, St. Petersburg, Florida: Advisor/Consultant Frederick S. Nolte, PhD, Karius: Stocks/Bonds
883. The Current State of Access: Inequitable Access to Infectious Disease Physicians in the Time of the COVID-19 Pandemic and Declining Fellowship Match Rates
Authors: Fuller Benjamin P , Strumpf Andrew , McManus Kathleen A
Published: November 2023

Background

Equitable access to specialty care is a key component of population health. Guidelines recommend specialty care within a 60-minute (min) drive. In 2017, 80% of United States (US) counties had no Infectious Diseases (ID) physicians. In the setting of the COVID-19 pandemic and declining fellowship match rates, we characterized inequities in geographic access to ID physicians in the US.

Methods

We geocoded the location of ID physicians from 2020 Medicare Provider Utilization and Payment Data. For people in the contiguous US, we conducted a cross-sectional analysis of one-way drive times to the closest ID physician overall and by age, gender, racial, and ethnic subgroups using 2020 US Census data. We calculated the median drive times and the proportion of each subgroup within x minutes to the nearest ID physician.

Results

We identified 6000 ID physicians at 2582 locations (Fig 1). Fig 2 demonstrates one-way drive times. In the US, 7.9% of people live > 60 min from ID specialty care. When stratified by rural/urban, 46.7% of rural people and 1.6% of urban people live > 60 min from the closest ID physician (Fig 3). Rural people had a median drive time of 57.2 min (95% CI 56.6-57.9) while urban people had a median drive time of 10.9 min (10.8-11.0). For people who identify as American Indian and Alaska Native (AIAN), 70.3% in rural areas and 8.8% in urban areas live > 60 min from the closest ID physician. For rural AIAN populations, median drive time was 95.1 min (86.0-104.1). For rural populations, the median drive time was > 60 min for those who identify as Native Hawaiian and Other Pacific Islander (69.1; 64.5-75.8), multiple races (65.5; 63.7-67.6), or Hispanic (66.9; 65.0-68.7).

Conclusion

Access to ID specialty care is inequitable. The largest disparities exist between rural and urban populations. Significant disparities exist for the AIAN population. In ID, we need recruitment and retention of our current workforce and recruitment of people who will serve rural and AIAN communities. If telemedicine continues to be supported, it could help to reduce disparities. This is also dependent on equitable access to high-speed internet, which is concentrated in urban/suburban areas. Without initiatives to expand the ID workforce and to increase internet access in rural areas, disparities in access will not improve.

Disclosures

Kathleen A. McManus, MD, MSCR, Gilead Sciences, Inc.: Stocks/Bonds
884. The Role of a Novel Inpatient Consultation Service for Persons Experiencing Homelessness in Detroit, Michigan: Finding Ways to Close the Gap
Authors: Joshi Seema , Elewa Nedda , Failla Andrew J , Mervis Madison , Furman Katerina , Ghanshani Sanjna , Leonardi Nyla N , Ilagan Roxanne , Zervos Marcus , Bryce Richard
Published: November 2023

Background

People experiencing homelessness (PEH) face inequitable social determinants of health that impact primary care prevention, complications related to infectious diseases (ID), and hospitalizations. The purpose of Street Medicine Organizations is to provide accessible medical care to PEH where they reside. We describe a uniquely developed hospital consult service (HCS) targeted for PEH.

Methods

This HCS took place in an 877-bed quaternary care hospital in Detroit, MI and occurred from 07/2022 – 03/2023. Inclusion criteria were PEH (defined as living unsheltered, sheltered, or with unstable housing). Figure 1a describes HCS timeline and objectives and aims of the HCS are shown in Figure 1b. The HCS template is shown in Figure 2. Healthcare screening (HS) recommendations were provided to the primary team, and discharge support including harm reduction education and community resources were provided to the patient. The outcomes evaluated included HS and vaccine orders and follow-up success on street medicine runs.

Consult note template

Results

60 patients were evaluated with the HCS from 09/2022 – 03/2023. Of those, 43 consults were completed prior to patient discharge. Patient characteristics are shown in Table 1. Median population age was 50 years, 44 (73.3%) were men and 46 (76.7%) were Black. Majority of patients seen (48.8%) were unsheltered. 31 patients (76.7%) had last seen a primary care provider > 12 months ago. Patient were more inclined to receive the influenza (30.2%) and pneumococcal (30.2%) vaccine compared to the COVID-19 vaccine (7%). 25 patients (58.1%) admitted to polysubstance use. There were recommendations placed for 23 (53.4%) of patients in which 11 (47.8%) were executed successfully prior to discharge. 17 (39.5%) patients had a scheduled follow up visit at a specific location and time on the street.

Conclusion

We describe the implementation of a unique HCS with a targeted needs assessment for PEH in hospital. Challenges regarding the HCS included frequent reeducation of HCS members to provide recommendations and sign-out. One major patient barrier included lack of phone for follow-up. However, specific gaps for this population within ID expertise have been identified. HCS future goals are to focus on harm reduction education, STI prevention, and addressing vaccine hesitancy in PEH.

Disclosures

Marcus Zervos, MD, Contrafect: Advisor/Consultant|GSK: Grant/Research Support|Johnson and Johnson: Grant/Research Support|Pfizer: Grant/Research Support
885. Promoting Diversity, Equity and Inclusion with a quarterly virtual Grand Rounds for the Pediatric Infectious Diseases Society
Authors: Rogo Tanya
Published: November 2023

Background

The Inclusion, Diversity, Access and Equity (IDA&E) Taskforce was created by the Pediatric Infectious Diseases Society (PIDS) in 2020. A 2021 survey of the PIDS membership to assess perceptions of diversity, equity and inclusion (DEI) revealed several areas of concern: perceptions of bias against and lack of support for international medical graduates (IMGs); lack of diversity in PIDS leadership; and perceived exclusivity in PIDS social and networking events. There is evidence that implicit bias can be alleviated by education that both increases awareness and provides bias reduction strategies. The Taskforce introduced a quarterly virtual Grand Rounds for the PIDS membership to provide DEI education. This abstract describes the first year of this initiative.

Methods

A proposal for a quarterly IDA&E Grand Rounds was approved by the PIDS Executive Committee in February 2022. A member of the IDA&E Taskforce assumed the role of course director. Four webinars were held in March, June, and September 2022, and January 2023. The topics addressed were under-representation in Pediatric Infectious Diseases, career challenges faced by IMGs, leadership development, and career pathways within Pediatric Infectious Diseases. A feedback survey link was provided to attendees of each Grand Rounds.

Results

The four Grand Rounds had an average of 172 registrants (range 130-204). Feedback survey completion was low (average 8 per webinar, range 4-18). Survey respondents reported affirmation of personal experiences; increased awareness of the topic discussed; and desire for more content related to career pathways, and IMG and visa-related concerns. Respondents commented on low attendance by division heads and fellowship program directors and recommended promotion of Grand Rounds attendance among persons in leadership positions.

Conclusion

Specialty-specific DEI education can be provided at the national level by a medical society through periodic webinars. The hour-long virtual format is limited in ability to address topics in-depth and should be the bare minimum of the work needed by institutions, training programs, and individual practitioners to support workforce diversity in Pediatric Infectious Diseases.

Disclosures

Tanya Rogo, MD, AstraZeneca: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support
904. Epidemiology of Rotavirus Group A Mixed Genotypes Isolated from Children with Acute Gastroenteritis over a 15-Year Period
Authors: Dellis Charilaos , Michos Athanasios , Tatsi Elizabeth-Barbara , koukou Dimitra-Maria , Syriopoulou Vasiliki
Published: November 2023

Background

Limited data exist worldwide regarding the genetic epidemiology of mixed G and/or P Rotavirus group A (RVA) strains and their association with demographic and clinical characteristics in children with acute gastroenteritis (AGE).

Methods

Positive fecal samples for mixed RVA previously G (VP7) and P (VP4) genotyped from children aged ≤16 years with AGE between 2007-2021 (15 years) in Greece were further genotyped for I (VP6) and E (NSP4) using RT-PCR and Sanger sequencing. Demographic, clinical and laboratory data of children infected with a mixed RVA strain were also collected.

Results

Over the 15-year period, 129/4427 (2.9%) mixed RVA strains were detected. Higher detection rate was observed in 2016 (7.5%) and in 2021 (5.8%) (Figure 1). Children infected with a mixed RVA strain had a median age of 21.1 months (IQR: 56.2) and were predominantly males (85/129, 65.9%). Mixed G genotype were 73/129 (56.6%), mixed P type 54/129 (41.1%) and both G and P mixed genotypes 3/129 (2.3%). In total, 27 different G/P combinations were detected with most prevalent the: G1G4P[8] (47/129, 36.4%), G1P[4]P[8] (18/129, 14%) and G4P[4]P[8] (18/129, 14%) (Figure 2). Higher seasonal peaks were observed for G mixed types in spring (68.8%) and for P mixed types in summer (66.7%). Infection with a G mixed type had a higher relative frequency in children aged 0-12 months, while infection with P mixed type had a higher relative frequency in children aged 13-48 months (p=0.043). I and E typing was successful in 49.6% (64/129) of mixed samples from 2013-2021. Two different I (I1, I2) and three different E (E1, E2, E3) genotypes were detected, with I1 (42.2%, 27/64) and E1 (39.1%, 25/64) being the most common I and E genotypes, respectively. In 31.3% (20/64) of samples, mixed I (I1I1, I1I2) and/or E (E1E1, E1E2) genotypes were also detected. No association has been detected between mixed genotypes and clinical characteristics of the patients.

Annual distribution of total and mixed RVA cases in a 15-year period

G-P combinations of RVA mixed strains.

Other combinations found in a smaller proportion (<2.3%) were: G3P[4]P[8] (1.6%), G4P[8]P[9] (1.6%), G6P[4]P[9] (1.6%), GUDP[4]P[8] (1.6%), G2G4P[4]P[8] (1.6%), G1G2P[4] (0.8 %), G1G3P[9] (0.8%), G1G8P[4]P[8] (0.8%), G10P[8]P[10] (0.8%), G12P[4]P[8] (0.8%), G2P[8]P[10] (0.8%), G2G4P[8] (0.8%), G2G9P[8] (0.8%), G4G12P[4] (0.8%), G8G9P[8] (0.8%), G9P[4]P[8] (0.8%), G9P[6]P[8] (0.8%), G9G12P[8](0.8%).

Conclusion

These results indicate the great genetic diversity of RVA strains. Significant differences were found in the seasonality of the mixed G and P strains as well as in the age group of children infected with mixed G and P strains.

Disclosures

All Authors: No reported disclosures
921. Clinical characteristics of hospitalized adults with herpes zoster in a Portuguese hospital: 11 years of experience
Authors: Pena Eduarda , Gonçalves Maria João M S , Azeredo Constança , Oliveira Susana , Araújo Sara , Moura Luís , Duarte Frederico , Jordão Sofia , Guimarães Mário , Abreu Ricardo Correia , Neves Isabel , Batista Clara
Published: November 2023

Background

Herpes zoster (HZ) results from the reactivation of latent varicella-zoster virus and commonly affects older or immunocompromised patients. Clinical manifestations include painful vesicular skin eruptions that normally respect a dermatomal distribution. Prognosis is normaly favorable but a minority of patients develop complications such as generalized infection, ocular involvement, meningoencephalitis or visceral dissemination. Post-herpetic neuralgia and secondary bacterial infections are frequent complications. Preventive strategies like vaccination are important to mitigate the burden of HZ.

Methods

This retrospective study reviewed the charts of all patients older than 18 years hospitalized in a Portuguese hospital with the diagnosis of herpes zoster infection diagnosis between January 1, 2012 and December 31, 2022.

Results

The study included 152 patients with a mean age of 70 years old; 58% were female. In terms of clinical manifestations: 47% suffered from localized herpes zoster (thoracic dermatome in 40%) and only 11% had generalized zoster. Other manifestations included meningitis/encephalitis (7%), keratitis (n=4) and Ramsay-Hunt syndrom (n=3). About half of patients (51%) had an identified cause of imunodepression upon hospital admission: 25% had malignancy on chemotherapy and 6% had a reumatic disead on immunossupressive therapy, only 7 patients were HIV positive. Most patients (78%) were treated with aciclovir (mean duration 9 days). Post-herpetic neuralgia and secondary bacterial infections were common (35% and 20%, respectively). All-cause in-hospital mortality was 6%.

Conclusion

Patients hospitalized for herpes zoster are frequently elderly people with comorbidities, especially cancer. Thoracic envolvement was most frequent in localized infection. Post-herpetic neuralgia and bacterial infections were frequent complications. Its important to implement preventive strategies such as vaccination for herpes zoster to prevent shingles and post-herpetic neuralgia in older adults, especially in those who are immunosupressed. This measure would probably help mitigate the burden of this disease in this population.

Disclosures

All Authors: No reported disclosures
923. EDP-938, A Respiratory Syncytial Virus (RSV) antiviral, demonstrates a high barrier to resistance in a human challenge study
Authors: Levene Rachel E , DeVincenzo John , Conery Annie , Ahmad Alaa , Goodwin Bryan , Or Yat Sun , Rhodin Michael
Published: November 2023

Background

RSV can cause substantial morbidity and mortality to populations at high risk and there are no approved direct acting antiviral treatments. EDP-938, an RSV nucleoprotein (N) inhibitor in Phase 2 clinical development, has demonstrated significant reductions in viral load and symptoms after 5 days of dosing in a human challenge study. In contrast to other mechanisms in development, such as fusion inhibitors, EDP-938 has a high barrier to resistance in vitro. Here, we characterize the clinical resistance profile from the EDP-938 challenge study.

Methods

To assess emerging resistance, the N gene was sequenced from nasal washes of RSV infected subjects at multiple timepoints before, during and after dosing. A subset of the 124 RSV infected subjects (37 EDP-938 and 11 placebo subjects, 159 total nasal wash samples) were chosen for sequence analysis based on viral load curves to encompass the range of patterns observed over the course of the study. Sequences were compared to baseline (RSV-A Memphis 37) and low frequency variant detection (< 1%) was performed.

Results

Of the 158 sequences obtained, no mutations identified in preclinical in vitro resistance studies were observed. Single N-protein mutations were detected in 2 subjects, both of whom received EDP-938. One subject had an E112G mutation detected on day 3 of treatment, however only wildtype virus was subsequently detected, and viral load became undetectable shortly thereafter. The other subject had an L139I mutation detected at days 4 and 5 of treatment and viral load was undetectable the next day. E112G and L139I viral variants were created by reverse genetics and tested for resistance and viral fitness in vitro. The E112G mutation did not confer resistance to EDP-938 nor any changes in viral fitness. The L139I mutation conferred very low-level resistance (10-fold decrease in EDP-938 antiviral activity) and a modest reduction in fitness.

Conclusion

In conclusion, no significant clinical resistance to EDP-938 was observed in this Phase 2 challenge study. These data demonstrate that EDP-938 has a high barrier to the development of clinical resistance.

Disclosures

Rachel E. Levene, PhD, Enanta Pharmaceuticals: Salary|Enanta Pharmaceuticals: Stocks/Bonds John DeVincenzo, MD, Enanta Pharmaceuticals: employee of Enanta Pharmaceuticals Annie Conery, Ph.D., Enanta Pharmaceuticals, Inc.: Stocks/Bonds Alaa Ahmad, PhD, Enanta Pharmaceuticals Inc.: Employee|Enanta Pharmaceuticals Inc.: Stocks/Bonds Bryan Goodwin, Ph.D., Enanta Pharmaceuticals: Former Employee|Enanta Pharmaceuticals: Stocks/Bonds Yat Sun Or, Ph. D, Enanta Pharmaceuticals: Co-inventor of EDP-938 patents|Enanta Pharmaceuticals: Stocks/Bonds Michael Rhodin, Ph. D, Enanta Pharmaceuticals Inc.: Employee of Enanta|Enanta Pharmaceuticals Inc.: Stocks/Bonds
1139. Immunogenicity and Safety Study of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) Compared to a Meningococcal Reference Vaccine (MCV4-TT) in Healthy Adolescents
Authors: Díez-Domingo Javier , Simkó Róbert , Icardi Giancarlo , Chong Chan Poh , Zocchetti Céline , Syrkina Olga , Bchir Siham , Bertrand-Gerentes Isabelle
Published: November 2023

Background

MenACYW-TT (MenQuadfi®) is a quadrivalent meningococcal conjugate vaccine licensed for use in individuals ≥ 12 months age in the EU and certain other countries and ≥ 2 years of age in the US. Safety and immunogenicity of a single dose of MenACYW-TT were evaluated in 10-17 years old healthy adolescents vs a quadrivalent (MCV4-TT [Nimenrix®]) meningococcal vaccine licensed ex-US. Co-administration of MenACYW-TT with 9vHPV and Tdap-IPV vaccines was also studied.

Methods

In this modified double-blind, Phase-3 study (NCT04490018) conducted in Hungary, Italy, Spain, and Singapore, meningococcal vaccine-naïve adolescents or MenC-primed (when < 2 years of age) were randomized to receive either MenACYW-TT or MCV4-TT and co-administration with 9vHPV and Tdap-IPV vaccines. Serum bactericidal assays with human complement (hSBA) were used to measure anti-meningococcal antibodies against all 4 serogroups at baseline and 30 days post-vaccination. Antibodies against antigens contained in Tdap-IPV and 9vHPV were also measured. Safety data were collected within 30 days post-vaccination.

Results

A total of 463 subjects were enrolled in this study. Non-inferiority between MenACYW-TT and MCV4-TT, based on seroprotection rate (percentage of subjects achieving hSBA titers ≥ 1:8), was demonstrated for all 4 serogroups one month following meningococcal vaccination. Thirty days post vaccination, hSBA geometric mean titers (GMTs) were higher for MenACYW-TT vs MCV4-TT for serogroups C, Y and W, and comparable for serogroup A. The percentages of subjects with an hSBA vaccine seroresponse were higher for MenACYW-TT vs MCV4-TT for all 4 serogroups (Table). When MenACYW-TT was administered alone or concomitantly with 9vHPV and Tdap-IPV vaccines, the immunogenicity results were comparable or higher in subjects receiving MenACYW-TT alone than in those receiving all vaccines concomitantly. The safety profiles were comparable between MenACYW-TT and MCV4-TT, administered alone or concomitantly with 9vHPV and Tdap-IPV vaccines, with no safety concerns observed during this study.

Conclusion

The trial met the primary objective. MenACYW-TT induced non-inferior immune responses to all serogroups based on seroprotection rates, and higher or comparable GMTs and seroresponse rates compared to MCV4-TT.

Disclosures

Céline Zocchetti, MSc, Sanofi: Stocks/Bonds Olga Syrkina, MD, Sanofi: Stocks/Bonds Siham Bchir, MSc, Sanofi: Sanofi's Employee|Sanofi: Stocks/Bonds Isabelle Bertrand-Gerentes, MD, Sanofi: Stocks/Bonds
1141. Incidence of adolescent syncope and related injuries following vaccination and routine venipuncture
Authors: Groom Holly C , Brooks Neon , Slaughter Matthew T , Mittendorf Kathleen , Naleway Allison L
Published: November 2023

Background

Vaccination is associated with syncope in adolescents. However, incidence of vaccine-associated syncope and resulting injury, and how it compares to syncope incidence following other medical procedures, is not known. Here, we describe the incidence of syncope and syncope-related injury in adolescents following vaccination and routine venipuncture.

Methods

We identified all Kaiser Permanente Northwest (KPNW) members ages 9 to 18 years with a vaccination or routine venipuncture and a same-day ICD diagnosis of syncope and collapse from 2013 through 2019. All cases were chart reviewed to establish chronology of events (vaccination, venipuncture, syncope, and injury, as applicable) and determine whether the event was attributed to vaccination or venipuncture. Incidence rates for vaccine- and venipuncture-associated syncope were calculated overall and by sex and age group. Incidence rates for vaccine-associated syncope were also calculated by vaccine type (Human Papillomavirus (HPV) vs. non-HPV).

Results

Of 197,642 vaccination and 12,246 venipuncture events identified, 549 vaccination and 67 venipuncture events had same-day codes for syncope. Chart validation confirmed 59/549 (10.7%) and 20/67 (29.9%) as vaccine-associated and venipuncture-associated syncope, respectively. Overall rates of syncope were 2.99 per 10,000 vaccination events (95% CI: 2.27-3.85) and 16.33 per 10,000 venipuncture events (95% CI: 9.98-25.21), yielding an incidence rate ratio of 0.18 (95% CI: 0.11-0.31). The incidence of vaccine-associated syncope increased with each additional simultaneously administered vaccine, from 1.51 (95% CI: 0.93-2.30) following a single vaccine to 9.94 (95% CI: 6.43-14.67) following 3 or more vaccines. When stratified by the number of vaccines received, rates of syncope were similar following vaccination events with and without the HPV vaccine. Among those with syncope events, documented injury occurred in about 15% of both vaccine and venipuncture events.

Conclusion

Syncope occurs more commonly following venipuncture than vaccination. A higher number of simultaneously administered vaccines is a risk factor for post-vaccination syncope in adolescents.

Disclosures

Kathleen Mittendorf, PhD, GE Healthcare: Grant/Research Support
1142. Impact of Informational Vaccine Notices Sent to Parents Prior to their Child’s 11th Birthday on Receipt of Adolescent Vaccines
Authors: Hanson Kayla E , Eggebrecht Meranda , Funk Penny , Christianson Ben , Belongia Edward , VanWormer Jeffrey J , Williams Charnetta L , McLean Huong
Published: November 2023

Background

Several vaccines, including human papillomavirus (HPV), tetanus-diphtheria-acellular pertussis vaccine (Tdap), and meningococcal serogroup ACWY vaccine (MenACWY), are recommended at age 11-12 years. In the United States, uptake of these vaccines, particularly HPV, is suboptimal. Systems to identify and notify patients who are coming due or overdue for vaccinations (reminder/recall) have been shown to be an effective strategy to increase vaccination. We assessed the impact of sending informational vaccine notices to parents of 10-year-old patients on receipt of adolescent vaccines in a predominantly rural, regional healthcare system in northcentral Wisconsin.

Methods

10-year-old patients with an upcoming 11th birthday (i.e., aged 10 years, 10 months or 10 years, 11 months) were identified at Marshfield Clinic Health System on a monthly basis and were randomized 1:1 to intervention (informational vaccine notice sent to the patient’s parent) vs. usual care (no notice). Randomization was stratified by rurality (rural, nonrural; defined by Rural-Urban Commuting Area Codes) and the parent’s preferred communication method (letter, text message, email). Receipt of adolescent vaccines (HPV, Tdap, MenACWY), as well as receipt of seasonal influenza vaccine and COVID-19 vaccine primary series, was assessed during the 90 days after randomization.

Results

From August 2021 through May 2022, 2,266 10-year-old patients were randomized (1,122 to the intervention and 1,144 to usual care) and 1,122 notices were sent to parents (576 letters, 544 text messages, and 2 emails). The majority of patients were non-Hispanic white (82%), lived in a rural area (63%), and approximately half were female (51%). Demographics did not vary by study arm. Receipt of HPV, Tdap, and MenACWY was 3.7 to 4.4 percentage points higher among patients randomized to the intervention vs. usual care (Table 1). No difference in uptake was observed for COVID-19 or influenza vaccines.

Conclusion

Informational notices sent to parents prior to their child’s 11th birthday resulted in modestly higher uptake of adolescent vaccines. Healthcare systems should consider sending vaccination notices, mailed or electronic, to parents whose children are coming due for recommended vaccines.

Disclosures

Kayla E. Hanson, MPH, Seqirus: Grant/Research Support Edward Belongia, MD, Seqirus: Grant/Research Support Huong McLean, PhD, MPH, Seqirus: Grant/Research Support
1154. Impact of Vaccination Protocol Implementation and Splenectomized Patient Management in a Specialized Clinic on Incidence of Encapsulated Bacterial Infections: a Retrospective Cohort Study in Quebec, Canada
Authors: Croft Émilie , Gingras-Lessard Florence , Musonera Jean Berchmans , Carignan Alex
Published: November 2023

Background

Splenectomy weakens immunity against encapsulated bacteria and is associated with increased overwhelming post-splenectomy infection rates. The impact of recommended vaccines for these bacterial infections has not been studied in Quebec. This study aims to i) assess changes in the incidence of encapsulated bacterial infections in patients who underwent splenectomy at Centre Hospitalier Universitaire de Sherbrooke (CHUS) from 1990 to 2019; ii) Investigate any changes in vaccine coverage following the implementation of: 1) a peri-splenectomy vaccination protocol in 2005 and 2) the creation of a clinic dedicated to splenectomized patients in 2015.

Methods

This retrospective cohort study selected splenectomy cases performed between 1990 and 2019 at CHUS. Bacterial infections (S. pneumoniae, H. influenzae, and N. meningitidis) were identified from electronic files of microbiology laboratories. Temporal trends were assessed over three periods according to the years in which pneumococcal polysaccharide and conjugate vaccines were recommended (1990–1998; 1999–2012; 2013–2019). The primary outcome was occurrence of vaccine-preventable infection within 5 years of splenectomy.

Results

The study included 544 splenectomized patients. The proportion of patients aged ≥65 years significantly increased over time [1990–1998: 30%; 1999–2012: 39%; 2013–2019: 44%; p=0.03]. S. pneumoniae [1990–1998: 6%; 1999–2012: 3%; 2013–2019: 0%; p=0.007] and H. influenzae infections significantly decreased [1990–1998: 11%; 1999–2012: 6%; 2013–2019: 0%; p=0.007]. Vaccination protocol implementation was associated with increase in the number of adequately vaccinated patients (Hib and PPV) in the 6 months after splenectomy [pre-protocol: 21%; post-protocol: 66%; p< 0.0001]. A significant difference between vaccination coverage (Hib, VPP, and VPC) in the 6 months after the splenectomy of patients seen in the immunization clinic (49%) and those not referred (8%) was observed (p< 0.0001).

Conclusion

Marked decrease in post-splenectomy infection rates was observed in our population over 30 years, despite aging. Vaccination protocol implementation and splenectomized patient management in a specialized clinic can improve vaccination coverage.

Disclosures

Alex Carignan, MD, MSc, GSK: Advisor/Consultant|GSK: Grant/Research Support|GSK: Honoraria|Moderna: Advisor/Consultant|Moderna: Honoraria|Orimed Pharma: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria
1159. A Phase 2 Drug-Vaccine Interaction Study of AV7909 and Ciprofloxacin or Doxycycline on Antibiotic Pharmacokinetics
Authors: Akintunde Gideon , Drobic Bojan , Bedell Lisa , Gan Lu , Kim Julia , Beah Marinda , Ghinai Isaac , Collado Santiago Barona
Published: November 2023

Background

AV7909 (Anthrax Vaccine Adsorbed, Adjuvanted) vaccine was developed for post-exposure prophylaxis (PEP) of disease following suspected or confirmed exposure to Bacillus anthracis administered in conjunction with recommended antibacterial regimen. A drug-vaccine interaction study (NCT04067011) was conducted to examine whether co-administration of AV7909 with ciprofloxacin (CIP) or doxycycline (DOX) affects antibiotic pharmacokinetics (PK) or AV7909 immunogenicity in healthy adults.

Methods

A Phase 2, randomized, open-label study was conducted to assess the effects of AV7909 (intramuscularly (IM) at 0, 2 weeks) on PK profiles of orally administered CIP and DOX in healthy adults between 18 and 45 years of age. Participants (n=210) were randomized to receive AV7909+CIP, AV7909+DOX or AV7909 alone. Serum concentrations of CIP and DOX were determined using liquid chromatography with tandem mass spectrometry, while AV7909 immunogenicity was evaluated using 50% neutralizing factor (NF50) values generated by a toxin neutralizing antibody (TNA) assay. Steady-state maximum concentration, Cmax and area under the curve from 0 to 12 hours, AUC0-12hrs for CIP and DOX were calculated. Safety was evaluated by collection of solicited reactogenicity and reports of adverse events (AEs).

Results

Primary PK endpoint for CIP was met, wherein 90% confidence intervals (CIs) of mean ratios for steady-state AUC0-12h [90% CI: 0.89, 1.07] and Cmax [90% CI: 0.87, 1.08] were contained within the equivalence criteria [0.80, 1.25]. The endpoint was marginally missed for DOX, wherein lower bound (LB) of 90% CI for AUC0-12h [90% CI: 0.82, 1.03] was within the equivalence criteria, but LB of 90% CI for Cmax (0.79) was below the equivalence criteria [0.80, 1.25]. This result for steady-state DOX Cmax is likely limited given that its efficacy is mainly AUC-driven. The immunogenicity endpoint was met, wherein LB of two-sided 95% CI of the geometric mean ratio of TNA NF50 was >0.5 (0.78 for CIP, 0.81 for DOX). The majority of solicited reactogenicities and AEs were Grade 1 or 2 in severity.

Conclusion

Co-administration of CIP or DOX with AV7909 did not alter the relevant PK parameters of antibacterials or immunogenicity of AV7909 and was well tolerated in healthy adults.

Disclosures

Gideon Akintunde, Director Clinical Development, Emergent Biosolutions: Employee Bojan Drobic, Director Clinical Development, Emergent Biosolutions: Employee Lisa Bedell, Director Biostatistic, Emergent Biosolutions: Employee Lu Gan, Director Biostatistic, Emergent Biosolutions: Employee Julia Kim, Scientist Clinical Development, Emergent Biosolutions: Employee Marinda Beah, Manager Clinical Trials Development, Emergent Biosolutions: Employee Isaac Ghinai, Medical Director, Emergent Biosolutions: Employee Santiago Barona Collado, Medical Director, Emergent Biosolutions: Employee
Effects of breed on preferential intake of hydroxychloride and sulfate sources of trace minerals in growing beef heifers
Authors: Souza Isabella R T , Moriel Philipe , Barbosa Murillo H , Rezende Maria E , Biazotto Felipe , Camargo Gian V A R , Augusto Karolina V Z , Porcionato Marco A F , Araujo Davi B , Vasconcelos José L M
Published: November 2023

This study evaluated the effects of breed on voluntary preferential intake of two sources of Cu, Mn, and Zn when added to white salt-based trace mineral supplement (days 0 to 55; experiment 1) and protein supplement (days 56 to 112; experiment 2). On day 0, Nelore and ½ Angus × ½ Nelore heifers (n = 20/breed) were stratified by breed, body weight (BW = 347 ± 82 kg), and age (12 to 30 mo), and randomly allocated into 1 of the 40 drylot pens (1 heifer/pen). Both experiments were divided into washout (days 0 to 27 in experiment 1 and days 56 to 83 in experiment 2) and preferential intake periods (days 28 to 55 in experiment 1 and days 84 to 112 in experiment 2). During the respective preferential intake period, heifers were provided simultaneous free-choice access to sulfate (SUL) and hydroxychloride (HYD) sources of Cu, Mn, and Zn mixed into salt-based trace mineral supplements from days 28 to 55 (experiment 1) and then protein supplements from days 84 to 112 (experiment 2). Heifers were provided free-choice access to Tifton 85 (Cynodon sp.) hay from days 0 to 112. Effects of breed × source × day of the study were detected (P ≤ 0.05) for daily trace mineral intake from days 28 to 56 and days 84 to 112. Angus × Nelore heifers consumed a greater amount of SUL vs. HYD supplements on days 31 to 33 (P = 0.02) and HYD vs. SUL supplements on days 37 to 42 (P ≤ 0.02), whereas Nelore heifers consumed more HYD vs. SUL supplements on days 31 to 33 and 43 to 51 (P ≤ 0.05). Both breeds consumed (P ≤ 0.05) a greater amount of protein supplement containing HYD vs. SUL from days 84 to 112, but the differences in protein supplement intake increased (P ≤ 0.04) in greater magnitude for Nelore vs. Angus × Nelore heifers. Supplement intake coefficient of variation (CV) from days 28 to 41 and days 84 to 97 tended (P = 0.06) to be greater for Nelore vs. Angus × Nelore heifers. Effects of breed × source were detected (P = 0.02) for supplement intake CV from days 84 to 112. Intake CV of supplements added with HYD did not differ (P ≥ 0.40) between Nelore vs. Angus × Nelore heifers but was greater (P < 0.01) for Nelore vs. Angus × Nelore heifers fed SUL supplements. Overall, Nelore heifers had greater preferential intake for mineral and protein supplements containing hydroxychloride vs. sulfate sources compared to Angus × Nelore heifers. Hydroxychloride sources encouraged voluntary intake and reduced variation in supplement consumption compared to SUL sources of the same metals.
Repeated radon exposure induced epithelial-mesenchymal transition-like transformation via disruption of p53-dependent mitochondrial function
Authors: Shan Shan , Chen Xiaoyu , Wang Aiqing , Yan Weici , Wu Qianqian , Wan Jianmei , Hong Chengjiao , Wang Yarong , Tong Jian , Tian Hailin , Xin Lili
Published: November 2023

Backgrouds

As a human carcinogen, radon and its progeny are the second most important risk factor for lung cancer after smoking. The tumor suppressor gene, p53, is reported to play an important role in the maintenance of mitochondrial function. In this work, we investigated the association between p53 and p53-responsive signaling pathways and radon-induced carcinogenesis.

Methods

After repeated radon exposure, the malignant characteristics, cell cycle arrest, cell apoptotic rate, adenosine triphosphate (ATP) content, reactive oxygen species (ROS) level, mitochondrial DNA (mtDNA) copy number as well as indicative biomarkers involved in mitochondrial energy metabolism were evaluated in BEAS-2B cells or BALB-c mouse lung tissue.

Results

Radon exposure induced epithelial-mesenchymal transition (EMT)-like transformation in BEAS-2B cells, as indicated by increased cell proliferation and migration. Additional mitochondrial alterations, including decreased ATP content, increased ROS levels, mtDNA copy numbers, cell apoptosis, and G2/M cell cycle arrest were observed. Radon exposure caused an energy generation shift from aerobic respiration to glycolysis as reflected by increased expression of TIGAR and p53R2 proteins and decreased expression of SCO2 protein in BEAS-2B cells, and increased expression of p53, SCO2 and TIGAR proteins in mouse lung tissue, respectively. The effects of p53 deficiency on the prevention of mitochondrial dysfunction suggested a protective role of p53 in radon-induced malignant-like features in BEAS-2B cells.

Conclusions

Repeated radon exposure induced EMT-like transformation in BEAS-2B cells via disruption of mitochondrial function. Activation of p53 and p53-responsive signaling pathways in BEAS-2B cells and BALB-c mice may confer a protective mechanism for radon-induced lung injury.
WHA Presidential Address 2023: Searching for a Redemptive West
Authors: Deverell William
Published: November 2023

This essay, a written version of the author’s October 27, 2023 Western History Association presidential address, asks about the West as space for redemption and exodus. Do Civil War histories and western histories offer hope of healing from the violence they engender? Or is every hopeful moment made destructive by violence, greed, and cultural blinders? Damaged Civil War soldiers went west and post-war Los Angeles became a place where many people imagined rebuilding their lives. White dreams proved exclusive: Angelenos burned out Chinese immigrants and shattered the western dreams of Black residents. Does writing new histories and ensuring that such violence is marked and remembered move toward hope? The essay considers both Civil War Era and contemporary redemption. Can remaking civic spaces around commemorations offer redemption? Los Angeles Chinese communities and their persistent efforts to hold space marking the1871 massacre as the city recreated downtown again and again could offer a model.
Oncogene goosecoid is transcriptionally regulated by E2F1 and correlates with disease progression in prostate cancer
Authors: Ge Yue , Ma Sheng , Zhou Qiang , Xiong Zezhong , Wang Yanan , Li Le , Chao Zheng , Zhang Junbiao , Li Tengfei , Wu Zixi , Gao Yuan , Qu Guanyu , Xi Zirui , Liu Bo , Wu Xi , Wang Zhihua
Published: November 2023

Background:

Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid (GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development.

Methods:

We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 (E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib.

Results:

GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment.

Conclusions:

GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.