Additional Dose Research Articles

Radiation Dose Savings Associated with Personalized CT Scan Range in 18F-NaF Bone PET/CT.

A disadvantage of 18F-NaF PET/CT compared with other types of bone scintigraphy is the additional radiation dose from the standard whole-body CT scan for lesion localization and characterization (L/C). This study investigated whether the L/C CT region can be personalized to reduce CT radiation dose, according to uptake in the PET images. Methods: Attenuation-corrected 18F-NaF PET images were reviewed for the clinically required L/C CT range by 1 medical observer and 1 technologist observer in 25 patients with breast cancer scanned before neoadjuvant chemotherapy. For each patient, effective doses were estimated for whole-body L/C CT, personalized L/C CT, and whole-body CT for attenuation correction only. Dose savings for the personalized method incorporating both whole-body CT for attenuation correction and personalized L/C CT were expressed relative to standard whole-body L/C CT. The clinical impact of the personalized method was determined by evaluating whether lesions clinically requiring coverage had been missed from the L/C CT region. Results: Potential dose savings of 43%-54% were estimated for the personalized CT method, according to the observers. From the 25 patients reviewed, the medical observer did not miss any clinically significant lesions from the L/C CT region, whereas the technologist observer missed 2 clinically significant lesions of 61 suggestive lesions identified by medical observer follow-up. Conclusion: Mean CT dose could be reduced by around half in this patient group with personalized CT. Future work should further evaluate whether this method can be implemented in clinical practice without compromising clinical image evaluation.

First-in-human trial of engineered NK cells in lung cancer refractory to immune checkpoint inhibitors.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality necessitating the exploration of alternate therapeutic approaches. Tumor reactive or activated-by-cytokine killers (TRACK) are PD-L1+ highly cytolytic natural killer (NK) cells derived from umbilical cord blood NK cells and engineered to express soluble IL15 (sIL15), showing promise in preclinical studies against NSCLC. We assessed safety, persistence, homing and cytotoxic activity in six patients with advanced, refractory, and progressing NSCLC who received a low dose of unmatched, allogeneic, off-the-shelf sIL15_TRACK NK cells. We evaluated NK cell presence and persistence with droplet digital (dd) PCR, flow cytometry, and immunofluorescent staining. sIL15_TRACK NK cells had peak measurements at one hour and became undetectable four hours after each in fusion. Cognate ligands to activating NK cell receptors were found in NSCLC. sIL15_TRACK NK cells were observed in a lung tumor biopsy seven days after the final infusion, confirming their sustainment and tumor-homing ability. They retained cytolytic function following isolation from the lung tumor. Three out of six patients achieved disease stabilization on repeat imaging, while the others progressed. Unmatched, allogeneic, cryopreserved, off-the-shelf sIL15_TRACK NK cells express activating receptors, home to tumor sites that express their cognate ligands, and retain cytolytic activity after infusion, underscoring their potential as a therapeutic approach in solid tumors. At low doses, the therapy was safely administered and showed preliminary evidence of activity in three of six patients with advanced and progressive NSCLC. Additional dose escalation cohorts and co-administration with atezolizumab are planned. gov NCT05334329FUNDING. Funding was provided by CytoImmune Therapeutics; CA266457; CA033572; CA210087.

Heterogeneity and Hierarchy of Immune Response to Primary Immunization in HIV-Infected Children on HAART and the Impact of an Additional Dose of Vaccine.

The nature of vaccine response inferiority is not well studied in children living with HIV (CLHIV). The authors investigated Hepatitis B Virus (HBV) and Diphtheria/Pertussis/Tetanus toxoid (DPT) vaccination responses following primary immunization in CLHIV (n = 42) and healthy controls (HC) (n = 38) and the effect of an additional vaccine dose. Antibody responses, CD4 and HBV-specific T/B cells were analysed using CMIA/ELISA and flow-cytometry. CLHIV had significantly lower baseline median antibody titres for all vaccines than HC (p <0.02). Differential seroprotection rates observed in CLHIV were, 4.8% for pertussis; 9.5% for HBV; 26.2% for diphtheria and 66.7% for tetanus. WHO staging significantly influenced anti-HBs levels (p = 0.0095). HBsAg-specific CD4+T-cells were significantly higher in CLHIV than HC (p = 0.042). An additional vaccine dose (HBV and Tdap) conferred a higher protection rate for tetanus and diphtheria (p <0.040) in CLHIV. These findings suggest that CLHIV exhibit a hierarchy of vaccine responses affecting antibody levels and protection rate, which was rescued by administering additional vaccine dose.

The role of citizenship in the acceptance and completion of COVID-19 vaccine cycle in the resident population with foreign citizenship registered with the Umbrian Health Care System - An analysis of regional data.

Non-italian citizens experienced less access to anti-COVID-19 vaccination, compared to the native population. Literature has found differences in adherence to anti-COVID-19 vaccination among these groups; however, there are apparently no studies that investigated the role of citizenship. Our objective was to investigate the role of citizenship in vaccine hesitancy toward anti-COVID-19 vaccination and the completion of vaccine cycle, in the non-Italian citizens resident in the Umbria Region. This is a population study, performed on resident population in Umbria. Population data were obtained thanks to a record linkage between the Regional Health Information System and the regional DBCOVID Umbria database. On this dataset, a descriptive and logistic regression analyses were performed. The 19.2% of non-Italian citizens did not take even one dose, 2.1% did not complete it and 40.6% did not take the additional dose. The range of values of which these results are an average, however, is very wide, suggesting important differences in COVID-19 vaccine up taking, among different citizenships. The logistic regression shows that citizenships with the highest probability of non-adherence to vaccination, compared to Philippine, was Romanian (OR=7.8), followed by Macedonian (OR=7.3) and Polish (OR=5.9). The study provides evidence of differences among citizenships that pinpoint the importance of understanding the reasons behind these behaviours, to support decisions around health policies tailored to each citizenship.

Surrogate gating strategies for the Elekta Unity MR-Linac gating system.

MRI-guided adaptive radiotherapy can directly monitor the anatomical positioning of the intended target during treatment with no additional imaging dose. Elekta has recently released its comprehensive motion management (CMM) solution that enables automatic radiation beam-gating on the Unity MR-Linac. Easily visualized targets that are distinct from the surrounding anatomy can be used to drive automatic gating decisions from the MRI cine imaging. However, poorly visualized targets can compromise the tracking and gating capabilities and may require surrogate tracking structures. This work presents strategies to generate robust tracking surrogates for a variety of treatment sites, enabling a wider application of CMM. Surrogate tracking strategies were developed from a cohort of patients treated using the CMM system on the Unity MR-Linac for treatment sites of the lung, pancreas, liver, and prostate. These sites posed challenging visualization or tracking of the primary target thereby compromising the tracking accuracy. Surrogate structures were developed using site-specific strategies to improve the imaging textured detail within the tracking volume while avoiding the dynamic overwhelming hypo- or hyper-intense anatomical structures. These surrogate volumes were applied within the anatomical positioning monitoring system as a proxy that drove the CMM gating decisions on the treatment unit. Robust site-specific surrogate structures were developed. Surrogate tracking structures for centrally located thoracic targets were created by expanding the target peripherally away from the heart and great vessels and into the lung. Pancreas surrogates required a vertically expanded column intersecting with the inferior liver edge. For the liver and prostate, surrogate structures consisted of a uniform expansion of the target, with liver surrogates intersecting the proximal liver edge or diaphragm while avoiding nearby ribs. These surrogate strategies have enabled the gating of complex moving targets among different treatment sites at our institution.

Reducing diltiazem-related hypotension in atrial fibrillation: Role of pretreatment intravenous calcium.

This study evaluated the efficacy of intravenous (IV) calcium pretreatment for preventing diltiazem-induced hypotension and assessed its safety in adult patients with atrial fibrillation (AF)/atrial flutter (AFL) with rapid ventricular response (RVR). This randomized, double-blind, placebo-controlled trial included 217 adults with AF/AFL and a ventricular rate>120 beats per minute, who were randomized into three groups: those who received an IV NaCl 0.9% placebo pretreatment prior to IV diltiazem (PD; 73 patients) and those who received 90mg (C90D; 71 patients) and 180mg (C180D; 73 patients) IV calcium chloride pretreatment before IV diltiazem. We compared participants' systolic blood pressure (SBP) and heart rate (HR) at baseline and at 5, 10, and 15min post-treatment, as well as the incidence of adverse events (e.g., hypotension, urticaria, nausea) among the groups. The PD and C90D pretreatment groups had significantly lower HR measurements at 10 and 15min compared to the C180D group. In addition, at 5min, the mean SBP in the PD group was significantly lower compared to the C90D and C180D groups. At 10min, the mean SBP was significantly higher in the C180D group than in the other groups. Furthermore, at 15min, the mean SBP was significantly higher in both the C90D and C180D groups than in the PD group. There were no significant differences between the calcium pretreatment and placebo groups in terms of the need for additional diltiazem doses or the incidence of adverse events. IV calcium pretreatment effectively prevents diltiazem-induced hypotension in patients with AF/AFL with RVR without compromising the efficacy of diltiazem in achieving and maintaining ventricular rate control. National Library of Medicine Clinical Trial Registry; No.: NCT06494007; URL: https://clinicaltrials.gov/study/NCT06494007.

WCN25-4036 Improved Outcomes with an Additional Rituximab Dose in Primary Membranous Nephropathy

WCN25-4036 Improved Outcomes with an Additional Rituximab Dose in Primary Membranous Nephropathy

Andexanet-induced Heparin Resistance in Cardiac Surgery - A Rapid Review of Case Reports and Series.

Andexanet alfa, a Food and Drug Administration (FDA)-approved antidote for apixaban and rivaroxaban, is used to manage life-threatening or uncontrolled bleeding. In patients undergoing cardiopulmonary bypass (CPB), prior exposure to andexanet can cause severe heparin resistance, necessitating effective mitigation strategies. A comprehensive review of such strategies remains lacking. To systematically review and characterize cases of andexanet-induced heparin resistance in patients undergoing CPB and to evaluate management strategies. A systematic search was conducted across multiple databases via the Ovid interface, Cochrane Central Register of Controlled Trials, and the FDA Adverse Event Reporting System. Quality appraisal was performed using a validated instrument for case reports and series describing drug-induced adverse events. Fourteen discrete patient cases met inclusion criteria. Post-andexanet administration, the mean initial activated clotting time (ACT) was 199.5 seconds, falling short of a target of >400 seconds despite additional heparin dosing (mean total: 1,123 U/kg). 35.7% of all cases involved thrombus formation in the reservoir; two of which required a circuit replacement. Antithrombin (AT) concentrate was administered to 75% of those received an adjunct therapy. A prophylactic AT use (mean, 49.9 IU/kg) resulted in an ACT over 400 seconds, while its effects in low-dose after the occurrence of thrombosis varied on ACT values. Nafamostat mesylate was used in some cases reported from Japan CONCLUSIONS: Heparin resistance following andexanet exposure poses significant procoagulant risk during CPB. Preemptive high-dose antithrombin therapy may improve ACT values. Further studies are needed to understand the mechanisms and optimize management of this condition.

A novel use of terbutaline: persistent genital arousal disorder in the emergency department

Persistent genital arousal disorder/genito-pelvic dysesthesia (PGAD/GPD) is a highly distressing, multifactorial disorder characterized by persistent unwanted physiologic genital arousal in the absence of sexual desire. This poorly understood disorder is thought to be derived from a complex dysregulation of biopsychosocial factors with common underlying neurological dysfunction that has yet to be adequately studied. With frequently evolving diagnostic criteria, lack of a standardized treatment algorithm, and few evidence-based treatment options, this disease is largely unrecognized and difficult to treat once identified. A 25-year-old woman presented to the Emergency Department (ED) with persistent and refractory symptoms of genital arousal not responsive to previously documented treatments, and the novel use of a β-adrenergic agent, terbutaline, leading to cessation of symptoms. With her initial presentation, lorazepam, haloperidol, and viscous lidocaine intravaginally provided relief for approximately 24 h until the patient returned. At her subsequent presentation, the patient received additional doses of lorazepam and intravaginal lidocaine, as well as consults with Urology and Obstetrics and Gynecology. Her symptoms eventually ceased by administration of terbutaline. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although presentation of PGAD to the ED is rare, emergency physicians should be prepared with treatment options to assist patients with this distressing diagnosis. This case highlights the novel use of terbutaline, a β-agonist, in cessation of PGAD symptoms when first-line benzodiazepines and antipsychotics fail.

Dose measurements with the Pille-ISS thermoluminescent dosimeter system during extravehicular activities (2004-2022).

One of the most problematic goals for radiation safety during spaceflight is an assessment of additional doses received by astronauts during extravehicular activity (EVA). The Pille-ISS thermoluminescent dosimeter developed by the predecessor of the Hungarian Research Network (HUN-REN) Centre for Energy Research (Budapest, Hungary) is designed for the routine dose measurements not only inside the spacecraft compartments, but also for personal dosimetric control for EVA. During almost two decades of the International Space Station (ISS) operation, the unique set of 131 EVA doses were recorded in different conditions, such as: solar activity, ISS trajectory along the South Atlantic Anomaly (SAA), and shielding conditions provided by two kinds of spacesuits: the Extravehicular Mobility Unit (EMU) and Orlan. The EVA dose rates during the normal scenario (without SAA crossing during EVA) are: 26 μGy/h on average, with maximum value of 118 μGy/h for the EMU spacesuit; and 103 μGy/h on average, with maximum value of 255 μGy/h for the Orlan spacesuit. However, the corresponding EVA dose can increase by about 33% on average regardless the spacesuit type, depending on time spent in SAA. The worst case mean EVA dose is equivalent to ∼ 7 days inside the ISS with 2.423 mGy. In general, the possible additional radiation risk due to the EVA is small in comparison with typical half-year mission onboard the ISS. The long-term experience of EVA dose assessments with Pille-ISS dosimeter shows that in some cases the skin dose can be underestimated due to the excessive shielding of the standard Pille-ISS dosimeter. To solve this problem, the modified Pille-ISS dosimeters with significantly reduced shielding are developed and involved onboard the ISS for the dose measurements starting from 2023.

Abstract TP368: Targeted Lipid Nanoparticles to Modulate Blood-Brain Barrier Transcytosis in Acute Ischemic Stroke

Ischemic stroke affects more than 600,000 Americans annually. Thrombectomy, where occluded arteries are cannulated for mechanical clot removal, can restore blood flow and improve survival, but still leaves 1/3 of patients functionally dependent, largely due to secondary ischemia-reperfusion injury. Brain edema in the acute phase of ischemia-reperfusion primarily associates with early-stage neurovascular damage and plays a major role in poor outcomes of stroke. Early on after ischemia/reperfusion, edema is mediated by increased transcytosis in the blood brain barrier (BBB) endothelium. Suppression of transcytosis has not yet been tested as a treatment for stroke. Major facilitator superfamily domain containing 2a (Mfsd2a) is a transporter protein that regulates caveolar transcytosis and is downregulated in ischemic stroke. We have previously demonstrated that 1) lipid nanoparticles loaded with mRNA (mRNA/LNP) enable rapid and robust protein expression; 2) vascular cell adhesion molecule (VCAM) targeting selectively delivers nanoparticles to stroke-affected BBB endothelium; 3) mRNA/LNP targeted to VCAM enabled protein expression in BBB endothelium. Therefore, we hypothesize that using LNPs containing Mfsd2a mRNA and targeted to vascular cell adhesion molecule (VCAM) can modulate Mfsd2a expression in inflamed BBB and improve outcome in ischemic stroke. In this work, we screened 10 LNP formulations and identified the optimized formulation on bEND.3 brain endothelial cells for Mfsd2a expression. The induction of Mfsd2a expression significantly enhanced Cav-1 expression and reduced the number of apical caveolae-formations by electron microscopy. Next, we used the acute ischemic stroke animal model (transient middle cerebral artery occlusion for 45 minutes) to assess the therapeutic outcome of VCAM-targeted LNP loaded with Mfsd2a mRNA. Right after reperfusion, we intravenously injected LNP and two additional dose every 24 hours (8ug RNA per dose). On day 3, we assessed brain edema by measuring the extravasation of radiolabeled albumin into the brain parenchyma. The percent of the extravasated albumin was significantly reduced after LNP treatment. In addition, using transmission electron microscopy, we observed less number of caveolae in the treated mice, compared to vehicle control. In conclusion, we have showed that VCAM targeted LNPs are able to deliver Mfsd2a mRNA to the inflamed brain vasculature and reduce brain edema by suppression of transcytosis.

BOVINE COLLAGEN EFFECT IN MAINTAINING BLOOD SUGAR AND BODY WEIGHT STABILITY IN DIABETIC RATS

Diabetes causes degenerative processes to occur earlier, for example during hyperglycemia with increased levels of Advanced Glycation End Products (AGEs) damaging the body's metabolism. Consuming anti-diabetic medications lowers blood sugar levels; however, hypoglycemia, which can be life-threatening, often occurs. Additionally, patients with diabetic experience uncontrolled weight loss or weight gain. This study aims to test the potential of bovine collagen in maintaining stable blood sugar levels and body weight in rats induced with diabetic. A total of 24 seven-month-old Wistar rats were divided into four groups: negative control group; positive control group induced with streptozotocin at 50 mg/kg body weight (BW) and given water as placebo; a group induced with streptozotocin at 50 mg/kg BW and treated with bovine collagen at a dose of 2x 400 mg/kg BW/day; and a third group of healthy rats receiving bovine collagen at the same dosage. All groups were treated for four weeks, during which body weight and blood sugar levels were monitored. The results indicated that diabetic rats treated with bovine collagen had better weight control compared to the positive control group in the first week (p = 0.033); however, in subsequent weeks, bovine collagen did not affect body weight. Blood sugar levels in the four groups of rats during the first, second, and third weeks showed that bovine collagen significantly reduced blood sugar levels in diabetic rats from the first to the third week (p &lt; 0.05). It is possible that additional doses or the administration of antioxidant flavonoids may be necessary from the second week onward to maintain weight stability.

Quantification and assessment of Day-To-Day interfraction set-up errors in radiotherapy treatment delivery based on EPID detector

Abstract Introduction: The aim of this study was to determine whether the EPID detector can serve as an effective tool for interfractional dose control. Accurate radiotherapy delivery is vital for successful treatment, prompting advancements in dosimetry methods, particularly for dynamic techniques. Linear accelerators use kilovoltage and megavoltage X-rays to verify patient positioning, a standard practice essential for minimizing geometric and dosimetric errors. While integrated imaging systems typically use orthogonal radiographs, this method increases radiation exposure and fails to account for intra-fractional movements, risking undetected errors. To ensure patients receive the planned radiation dose, in-vivo dosimetry is performed by measuring the dose at various locations on the patient's body, which simultaneously verifies correct positioning. Discrepancies can reveal incorrect positioning or significant movements, thus enhancing treatment accuracy. This study investigates transit dosimetry using Electronic Portal Imaging Devices (EPID) to verify patient positioning during treatment. It establishes tolerance ranges and response criteria for the head and neck and pelvic areas, providing insights into the concordance between planned and actual dose distributions. Material and methods: The analysis included 30 patients treated with dynamic techniques in the pelvic (Pelvis) and head and neck (Head&amp;Neck) areas. For each fraction, a fluence map was recorded using the EPID detector. This allowed for repeated comparisons between summary fluence maps across treatment fractions, totaling 1552 comparisons for the Head&amp;Neck area and 2339 for the Pelvis area. To evaluate the correspondence between fluence map pairs, gamma indices were calculated using specified accuracy criteria. Results: Statistical analysis employed Chi-squared or Fisher's exact test, establishing significant correspondence within defined limits. For the Head&amp;Neck area, repeatability was found within 3 mm and 4%; for the Pelvis area, it was within 4 mm and 4%. Conclusions: This method of verifying treatment repeatability is practical for clinical use, requiring no additional dose and not hindering treatment delivery.

P-2047. Public Health Impact and Economic Value of an Additional Dose of Pfizer-BioNTech XBB.1.5-adapted COVID-19 Vaccine for Older Adults in the United States

Abstract Background To assess the public health impact and economic value of an additional dose of BNT162b2 XBB.1.5-adapted COVID-19 vaccine 6 months after initial dose for those aged ≥65 years, compared to a single dose in the United States.Table 1.Clinical and Economic Outcomes of 2-dose vs 1-dose Strategy in the Population Aged ≥65 Years.LY = life year; QALY = quality adjusted life year; ICER = incremental cost effectiveness ratio Methods A combined Markov and decision tree model was used to estimate the public health impact of those aged ≥65 years receiving an additional BNT162b2 XBB.1.5-adapted dose over for a one-year time horizon (Oct 2023-Sept 2024). Age-stratified (65-74, 75+) annual attack, hospitalization, and vaccine coverage rates were informed by public health national surveillance data. Other age-stratified clinical, cost, and vaccine effectiveness parameters were informed by publications. Parameter uncertainty was examined through scenario and sensitivity analyses. Conservatively, indirect effects (e.g. reduced transmission) and broad societal benefits were not considered. Results For individuals aged 65 years and older, the model demonstrated that compared to a single dose, an additional dose of the BNT162b2 XBB.1.5-adapted COVID-19 Vaccine resulted in 338,148 fewer symptomatic cases, 19,947 fewer hospitalizations, and 591 fewer deaths. Cost of additional vaccinations were offset by costs averted (e.g., Long COVID (∼$1.3B), inpatient (∼$384M), indirect (∼$280M), and outpatient (∼$252M) costs), leading to a total cost savings of ∼$270.5M. The two-dose strategy for older adults improved health outcomes and lowered costs resulting in a dominant ICER (Table 1). The additional dose was predicted to be a budget-efficient solution for payers. Results were most sensitive to variation in the symptomatic rate of infection and the hospitalization rate. Conclusion An additional dose of BNT162b2 XBB.1.5-adapted COVID-19 vaccination for adults aged 65 years and older in the US may generate notable reductions in symptomatic cases, hospitalizations, and deaths and result in cost savings. The results demonstrate that administering an additional COVID-19 vaccine dose to older adults in the US should be an important public health goal, supporting current ACIP and CDC recommendations. Disclosures Alon Yehoshua, PharmD, MS, Pfizer Inc: Employer|Pfizer Inc: Stocks/Bonds (Public Company) Benjamin Yarnoff, PhD, Pfizer Inc: Grant/Research Support Manuela Di Fusco, PhD, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Santiago M.C. Lopez, MD, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Elizabeth A. Thoburn, MPH, Pfizer Inc: Employer|Pfizer Inc: Stocks/Bonds (Public Company) Abby Rudolph, PhD, Pfizer Inc: Employer|Pfizer Inc: Stocks/Bonds (Public Company) Kinga Marczell, PhD, Pfizer Inc: Grant/Research Support

Use of music as an adjunct for sedation in transoesophageal echocardiography

Abstract Background Transoesophageal Echocardiography (TOE) is semi-invasive examination used for cardiac evaluation, frequently associated to a certain degree of anxiety, and often requiring sedation for patient comfort; alternatively, sedation can result side effects such as hemodynamic changes (hypotension) or hypoventilation and hypoxemia. Music has been used as a non-pharmacological strategy to reduce stress and anxiety levels during medical procedures; accordingly, we hypothesized that music could be used to decrease anxiety and/or sedation dose in patients referred for TOE. Methods 63 patients over 18 years old undergoing TOE were randomized either to intervention (music group, 31 patients) or no intervention (control group, 32 patients); music was started before transthoracic echocardiography (TTE) and continued up to the end of TOE; an anxiety mini query consisting in 4 degrees of anxiety levels (no, mild, moderate and high) was answered before transthoracic echocardiography (TTE) and again just before sedation; data regarding hemodynamic status (blood pressure, heart rate, oximetry and respiratory incursions ) were examined before and after the intervention; additionally, groups were compared regarding administered total midazolam dose (initial dose plus additional doses). Results There was no difference between the groups regarding age (55.1 ±13.7 years vs 49.8± 15.5 p = NS), sex, ethnics, body mass index or the presence of comorbidities . Both groups presented a decrease in anxiety levels before TOE (p = 0.04), however the decrease was more substantial with music compared to control (p&amp;lt; 0.008). Hemodynamic variables were unchanged, except for diastolic blood pressure (p=0.03), showing a slight but significant decrease after music (Table). No difference was seen in the total midazolam dose between the groups (median 5.0 mg with range [4.5 - 7.0 mg] vs 5.0 mg [4.0 - 8.0 mg], p = 0.4; additionally, a negative correlation was found for midazolam dose and age, whereas no correlation was found for other hemodynamic parameters. Conclusion Despite no reduction in sedation dose in patients assigned for TOE, listening to music decreases the degree of anxiety, with a small decrease in blood pressure; therefore, music could be useful as an adjunct to sedation in this scenario.

P-721. Risk Factors Associated with COVID-19 Among Fully Vaccinated Healthcare Workers in Lima, Peru

Abstract Background Healthcare workers (HCWs) are an important target group for COVID-19 vaccination. In February 2021, Peru launched a COVID-19 vaccination campaign among HCWs using a BBIBP-CorV inactivated whole-virus vaccine (Sinopharm). We aim to understand risk factors for SARS-CoV-2 infection after vaccination using a cohort of HCWs in two hospitals in Lima, Peru. Methods Between August 2021-June 2022, HCW who received at least two COVID-19 Sinopharm vaccine doses were enrolled in the cohort and followed for 6 months. Participants provided a self-collected nasal swab weekly for SARS-CoV-2 by reverse transcriptase polymerase chain reaction testing. SARS-CoV-2 infection was confirmed by a positive PCR test result at least 14 days after receiving the second vaccine dose. Adjusted hazard ratios (aHR) were used to identify associations with infection accounting for potential confounding. Person-time was calculated based on days between negative PCR results, capped at 10 days; in cases of infection, the time between positive and negative tests was halved, with half the days considered at risk. Results Of 670 vaccinated HCWs, 111 (16.6%) tested positive for SARS-CoV-2 during the follow-up period. In adjusted models, prior report of COVID-19 illness in the previous 12-months was associated with reduced risk of infection (aHR: 0.98 [95% CI:0.97‒0.99], p=0.026). Being beyond 6 months since the last vaccination was significantly associated with an increased risk of infection (aHR: 3.22 [95% CI:1.66‒6.23], p=0.0001) as well as working in an outpatient setting (aHR: 1.94 [95% CI:1.06‒3.53], p=0.031). Conclusion In this cohort of healthcare workers undergoing regular asymptomatic COVID testing, our findings suggest evidence of waning protection at 6 months post-vaccination BBIBP- CorV. Additionally, preliminary indications suggest that healthcare worker behaviors or specific occupational exposures may contribute to increased infection risk even following vaccination. In addition, these results support the inclusion of HCWs as a priority group for additional booster doses of COVID-19 vaccine at 6 months after the most recent dose. Disclosures All Authors: No reported disclosures

P-1659. Clinical and Safety Outcomes of Uniform Thrice-Weekly Daptomycin Dosing Based on Adjusted Body Weight in Patients Receiving Intermittent Hemodialysis

Abstract Background Limited evidence exists on optimal dosing of daptomycin (DAP) in patients receiving intermittent dialysis (HD). Current labeling recommends every 48 hour (q48h) dosing which often causes additional DAP doses to be given throughout the week when the schedules become unaligned. Alternatively, current recommendations for thrice weekly dosing suggest a larger dose for the 72-hour interdialytic interval, which makes operationalization difficult within current inpatient electronic systems. Methods A retrospective observational cohort study comparing clinical and safety outcomes of adult patients receiving DAP with HD was performed between 01/2021 and 04/2024. Updated dosing recommendations for DAP with HD was modified on 1/2023 to indication based uniform adjusted body weight (AdjBW) dosing with each HD session compared to the previous recommendation of q48h based on total body weight. Clinical outcomes included microbiologic recurrence and escalation of dose or antibiotic therapy. Safety outcomes included CK elevation and development of rhabdomyolysis. Patients were excluded if they were on DAP prior to admission or received &amp;lt; 2 DAP doses. Results In total, 79 patients met inclusion. BMI, acuity of infection, length of stay, and duration of therapy were similar between the q48h (n=42) and the with each HD groups (n=37). There was a significant reduction in total weekly AdjBW DAP received in the with each HD group (23.8mg/kg vs 28.8 mg/kg, p &amp;lt; .0001) despite a higher utilization of the 8 mg/kg strategy (64.9% vs 26.2%). There was no significant difference in the clinical failure (5.4% vs 4.8%, p = 0.90) or safety outcomes (0% vs 6.5%, p = 0.12) between the post- and pre-groups, including after propensity matching based on BMI, AdjBW dose received, and receipt of source control. Conclusion Utilizing uniform DAP doses with each HD compared to standard q48h frequency in patients receiving HD did not result in worse clinical or safety outcomes while reducing the overall weekly exposure to DAP. This strategy further supports the use of AdjBW as the preferred dosing weight for DAP, including in HD patients, who have been underrepresented in previous studies. This method could also be useful in the outpatient setting to help optimize DAP exposure. Disclosures All Authors: No reported disclosures

218. Attenuated PreFusion F Antibody Response to RSV Vaccines in Solid Organ Transplant Recipients

Abstract Background RSV causes serious morbidity in solid organ transplant recipients (SOTRs). Novel RSV vaccines are highly protective in the general population, yet immunogenicity among SOTRs is unknown. Demographic and Transplant Characteristics of SOTRs Reporting RSV Vaccination Methods Within a national, prospective cohort study SOTRs submitted whole blood samples at baseline and 2, 4, and 12 weeks post receipt of RSV vaccination (RSVPreF3 [GSK, AREXVY™] or RSVpreF [Pfizer, ABRYSVO™]) between October 2023-March 2024. Plasma prefusion F IgG and IgM (preF Ab) was tested using the Meso Scale Discovery platform and compared between baseline and 4 weeks to assess fold-change (FC); the proportion achieving high-titer Ab (IgG ≥high-titer reference plasma [BEI Resources]) at 4 weeks was also assessed. Ab measures were compared between GSK and Pfizer vaccinees. Change in Prefusion F IgG Titers following RSV Vaccination in SOTRs Blue dots represent Pfizer vaccine recipients and pink dots represent GSK vaccine recipients. Individual titer trajectories are connected by grey lines. High-titer response is denoted by the upper red horizontal line, corresponding to high-titer pooled control plasma. Results Among 27 participants (median [IQR] age 65-73 years, 44% female, 59% GSK and 30% Pfizer vaccinees [11% unspecified]), median [IQR] preF IgG rose from 76,252 [59,116-185,845] to 424,618 [153,503-1,905,705] AU/mL by 4 weeks (median [IQR] FC 5.54 [2.06-13.26]). Overall, 67% demonstrated IgG FC ≥4 at 4 weeks (69% GSK vs 50% Pfizer vaccinees) and 52% demonstrated high-titer Ab at 4 week (62% GSK vs 25% Pfizer vaccinees); clinical and transplant factors were similar between response groups. By 12 weeks, 56% showed high-titer Ab (62% GSK vs 38% Pfizer vaccinees) (Figure). Response patterns varied, including greater IgM change from baseline to 4 weeks in GSK vaccinees (IgM FC ≥4: 31% GSK vs 25% Pfizer) and more pronounced IgG peak-and-wane in GSK vaccinees (median FC from 4 to 12 weeks 1.01 GSK vs 0.49 Pfizer). No participants reported RSV infection during follow up. Prefusion F IgG Titers pre and post RSV Vaccination in SOTRs, by Vaccine Type Blue dots represent Pfizer vaccine recipients and pink dots represent GSK vaccine recipients. High-titer response is denoted by the upper red horizontal line, corresponding to high-titer pooled control plasma. Open circles represent ≥ 4-fold change in titer at 4 weeks. Conclusion RSV preF Ab responses are highly variable and often attenuated in SOTRs following RSV vaccination; 44% did not show high-titer Ab at 4 weeks. Response level and pattern vary by vaccine platform (i.e., adjuvanted versus unadjuvanted), which may imply different risk periods post vaccination and potential role for additional vaccine doses to improve immunoprotection. Prefusion F IgM Titers pre and post RSV Vaccination in SOTRs, by Vaccine Type Blue dots represent Pfizer vaccine recipients and pink dots represent GSK vaccine recipients. Open circles represent ≥ 4-fold change in titer at 4 weeks. Disclosures Andrew H. Karaba, MD PhD, Hologic: Advisor/Consultant William Werbel, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Honoraria|IDSA: Advisor/Consultant|Novavax: Advisor/Consultant

P-2231. The Impact of Cell-free DNA Sequencing in the Evaluation and Management of Infections

Abstract Background Cell-free DNA Sequencing is a novel diagnostic test that utilizes next generation sequencing to detect pathogens directly from plasma. Microbial cell-free DNA (mcfDNA) can be detected for a large number of pathogens with high analytic sensitivity and specificity; however, testing may be cost prohibitive and the direct impact on clinical care decisions is unclear. Methods A retrospective review was performed at a large inner-city tertiary care medical center from 9/2021 to 3/2024 to assess the results of mcfDNA sequencing (using the Karius Test®) on committee approved patients for whom infection was suspected, and without a definitive diagnosis on traditional microbiologic testing or in patients not improving on current antimicrobial therapy. Clinical, microbiologic, and outcome data were collected, and the impact of a positive or negative test on clinical care decisions was abstracted. Test results were defined as impactful if they led to change in the antimicrobials (e.g. additional agents, dosing adjustment, or discontinuation of antimicrobials). Results Testing was completed on 25 patients, ranging from 5 months to 63 years (mean age 17 years), 16 (64%) female, 12 (48%) immunocompromised. The average result reporting time was 2.6 days. 23 (92%) patients received antibiotics prior to testing with an average duration of 30.8 days. A total of 13 (52%) of tests were positive by mcfDNA (with a mean of 1.6 organisms (SD=0.65) detected), and 7 (53.8%) polymicrobial results. The positive vs negative did not vary by suspected site, though sample size was small (Fig1). A total of 15 (60%) patients were positive by traditional microbiology tests with an organism correlation of 5 (20%). The mcfDNA results were impactful in 9 (36%) of the patients. A positive test was more likely to be impactful than a negative test (p=0.01). Ninety-day mortality was noted in 10 (40%) of patients and the average duration of hospitalization was 75.5 days – with no difference among patients with a positive mcfDNA (Table 1). Conclusion A positive mcfDNA sequencing result was noted to be clinically impactful in 36% of cases. Our data suggests that testing would be most beneficial for patients that lack a definitive infectious diagnosis or those not responding to appropriate therapy. Disclosures All Authors: No reported disclosures

P-2054. Effectiveness of a Single COVID-19 mRNA Vaccine Dose in Individuals Previously Infected with SARS-CoV-2: A Systematic Review

Abstract Background Based on the high levels of population immunity to SARS-CoV-2 from prior infection in many countries, in fall 2023 the US Food and Drug Administration, European Medicines Agency, and World Health Organization authorized/recommended a single mRNA XBB.1.5-adapted vaccine dose for unvaccinated individuals aged ≥ 5y. Methods This systematic literature review evaluated the vaccine effectiveness (VE) of a single COVID-19 mRNA dose (BNT162b2 or mRNA-1273) in individuals previously infected with SARS-CoV-2 compared to those with differing histories of prior infection and vaccination (PROSPERO ID: CRD42023453257). We searched MEDLINE and Embase for VE studies published from January 1, 2021–October 4, 2023. Data were synthesized following Synthesis Without Meta-Analysis guidelines. Bias was assessed using the Newcastle-Ottawa Scale. VE estimates were reported as a range of point estimates per clinical endpoint and meta-analyses were not performed due to heterogeneity. Results Of 1,661 initial results, 18 studies were eligible for inclusion. Among those previously infected, a single mRNA dose (compared to being unvaccinated) increased protection by 8–71% against infection (related to Omicron BA.1, BA.4/5, or XBB), 39–67% against symptomatic infection (BA.1, BA.2, or BA.4/5), and 25–60% against hospitalization or hospitalization or death (BA.1). The protection provided by a single dose among those previously infected was comparable to the VE provided by two doses, and was higher than VE following two doses without prior infection. No studies were identified that reported single-dose VE for adapted vaccines (BA.1 or BA.4/5 bivalent or XBB.1.5-adapted formulations), immunocompromised populations, or children aged &amp;lt; 5y. Conclusion Our results suggest that a single dose of COVID-19 vaccine provides similar protection to that conferred by a two-dose series for immunocompetent individuals aged ≥ 5y in the current setting of high pre-existing SARS-CoV-2 immunity. These findings support current recommendations for one dose of COVID-19 vaccines regardless of vaccination status to be given in advance of the viral respiratory season with considerations for additional doses for certain special populations including young children, older adults, and the immunocompromised. Disclosures Hannah R. Volkman, PhD, MPH, Pfizer Inc: Employment|Pfizer Inc: Stocks/Bonds (Public Company) Jennifer L Nguyen, ScD, MPH, Pfizer Inc: Employment|Pfizer Inc: Stocks/Bonds (Public Company) Mustapha M. Mustapha, MD, PhD, MPH, Pfizer Inc: Employment|Pfizer Inc: Stocks/Bonds (Public Company) Jingyan Yang, MHS, DrPH, Pfizer Inc: Employment|Pfizer Inc: Stocks/Bonds (Public Company) Luis Jodar, PhD, Pfizer Inc: Employment|Pfizer Inc: Stocks/Bonds (Public Company) John M. McLaughlin, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company)