bluuebunny/crossref_metadata_2025_split huggingface dataset:
215a. Use of Viracor Cytomegalovirus T-Cell Immunity Panel (TCIP) to Predict the Risk of Recurrent Cytomegalovirus Infection in Solid Transplant Patients and Guide Appropriate Management
Authors: Vysniauskaite Indre , Guo Kexin , Angarone Michael P , Stosor Valentina , Tanna Sajal D , Ison Michael G 
Published: December 2022

Abstract

Background
Cytomegalovirus infection (CMV) is the most common opportunistic infection in solid organ transplant recipients (SOTR). Predicting recurrent disease and appropriate use of secondary antiviral prophylaxis is currently poorly defined. CMV-specific T-cell assays have been shown to be promising tools in determining presence of CMV immunity and helping guide primary and secondary antiviral prophylaxis. The goal of this study was to evaluate the ability of commercially available CMV-TCIP in predicting the risk of CMV relapse.

Methods
After IRB approval, clinical and laboratory data was retrospectively collected from our Enterprise Data Warehouse and primary chart review on 74 SOTR. As part of routine clinical care, the CMV T-Cell Immunity Panel (CMV-TCIP, Viracor Eurofins, Lenexa, KS) were collected by the TID provider managing the infection; generally this was done around the time of first negative test to inform choice of 2° prophylaxis. Analysis was completed for the total patient population and a subgroup of patients with CMV-TCIP tests completed ± 21 days of the first negative CMV VL. Descriptive statistics and Cohen’s Kappa statistics were used to assess association of relapse with assay results.

Results
Patient demographics are shown in Table 1. 2° prophylaxis was given to 60 (81.1%) of total patients for a mean of 86 days (0-614 days) after the first negative CMV VL. 26 (35.1%) SOTRs had relapse – 9 with positive CD4 and 20 with positive CD8 CMV-TCIP values. There was no association between specific test results and risk of relapse in the overall study population (see table 2). Similarly, no significance was found in the subgroup analysis of patients with CMV-TCIP results ± 21 days after first negative CMV VL.

Conclusion
In this study, CMV-TCIP did not predict CMV relapse after initial infection and treatment. While prior studies have shown a potential role for assessment of CMV-specific immunity to guide need for secondary prophylaxis, more studies of the CMV-TCIP are needed to assess the utility of this assay for this indication.

Disclosures
Michael P. Angarone, DO, Abbvie: Advisor/Consultant Valentina Stosor, MD, DiaSorin: Advisor/Consultant|Eli Lilly and Company: Grant/Research Support|Med Learning Group: Honoraria Michael G. Ison, MD MS, GlaxoSmithKlein: Grant/Research Support|Pulmocide: Grant/Research Support|Viracor Eurfins: Advisor/Consultant.
215b. Real-World Experience of Letermovir Use at an Academic Transplant Center
Authors: Ryu HaYoung , Bowen Christina , Bubalo Joseph , Yu Diana , Lewis James S 
Published: December 2022

Abstract

Background
Letermovir (LMV) is indicated for cytomegalovirus (CMV) prophylaxis in seropositive adults after allogeneic hematopoietic stem cell transplants (alloSCT). LMV is well tolerated compared to its alternatives. Our institution restricts LMV use to high-risk patient groups to maximize the cost/benefit of LMV. Despite these restrictions, LMV was in our institution’s top 50 drug expenditures, prompting a formal evaluation of its use. We describe a real-world experience with LMV at a 576-bed academic transplant center.

Methods
This was a single center, retrospective, descriptive study of LMV use at a transplant center. Any hospitalized patient who received ≥ 1 dose of LMV between August 2021 and January 2022 was eligible for analysis. Data collection included age, LMV administration data, length of stay, transplant status, Infectious Diseases (ID) consultation, documented rationale for non-criteria uses, and drug cost. The primary outcome was incidence of use not aligning with restriction criteria. The secondary outcome was institutional drug expenditure for non-criteria uses compared to approved uses.

Results
Over 6 months, 388 doses of LMV were administered to 31 unique patients during 41 admissions. LMV use during 12/41 admissions (31.7%) fell outside the institutional criteria. ID consult occurred in 58.3% (7/12) of cases. 27/31 (87%) were alloSCT patients, including 1 pediatric patient. There was also 1 liver and 1 heart transplant recipient. Reasons for non-criteria use were: primary prophylaxis in the heart transplant patient to avoid ganciclovir toxicity and in 2 alloSCT patients without high risk for CMV, pre-emptive therapy due to CMV reactivation (n=2), and step-down therapy for CMV viremia (n=4). LMV was used for extended periods ( &gt; 100 days from transplant) in 2 cases. Non-criteria use of LMV accounted for $20 414 in drug cost over 6 months, 29% of total expenditure.

Conclusion
Our data suggest real world use of LMV often differs from the patient types enrolled in the phase 3 trials. Use of LMV as an alternative to available CMV therapies to avoid drug toxicities appears to drive much of this use. In addition, use outside of criteria was frequent and incurred a nontrivial cost. Modification of our criteria, such as requiring an ID consultation for off-label use, should be considered.

Disclosures
James S. Lewis, PharmD, FIDSA, Cidara: Advisor/Consultant|Merck: Advisor/Consultant|SeLux Diagnostics: Advisor/Consultant.
226. Higher Doses of Adintrevimab, an Extended Half-Life Monoclonal Antibody, for the Treatment and Prevention of COVID-19: Preliminary Results from a Phase 1 Single Ascending-Dose Study
Authors: Pu Xia , Gong Jean , Campanaro Ed , Narayan Kristin , Gupta Deepali , Engler Frank , Copans Amanda , Schmidt Pete 
Published: December 2022

Abstract

Background
Adintrevimab is a fully human IgG1 monoclonal antibody engineered to have potent and broad neutralization against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other SARS-like CoVs with pandemic potential. Adintrevimab is being assessed in two separate phase 2/3 clinical trials: the EVADE trial for prevention of COVID-19 in both post-exposure and pre-exposure settings and the STAMP trial for treatment of COVID-19. Here we report higher doses being evaluated in a healthy volunteer study given that emerging variants may have varying susceptibilities to adintrevimab. Previous results 300 mg IM, 600 mg IM, and 500 mg IV cohorts have been reported.

Methods
This is an ongoing Phase 1, randomized, placebo (PBO)-controlled, single ascending-dose study of adintrevimab administered intramuscularly (IM) or intravenously (IV) to healthy adults aged 18–50 years with no current SARS-CoV-2 infection. Participants were randomized 8:2 in 3 high dose cohorts (N=10/cohort: n=8 adintrevimab, n=2 PBO): adintrevimab 1200 mg IM, 1200 mg IV, and 4500 mg IV. Safety, tolerability, and pharmacokinetics (PK) were assessed up to 21 days post dose.

Results
Overall, 30 participants received adintrevimab (n=24) or PBO (n=6). Blinded safety data for all cohorts and PK for 1200 mg IV are reported. Through 21 days post dose all doses were well-tolerated, with no study drug-related adverse events (AEs), serious AEs, injection site reactions, or hypersensitivity reactions reported. The observed PK profile of the 1200 mg IV dose included Cmax of 423±105 µg/ml. Comparison of 500 mg and 1200 mg IV doses indicate dose proportionality of Cmax and exposure (AUC Day 21).

Conclusion
A single dose of adintrevimab, up to 4500 mg, was well tolerated. These preliminary safety data and PK support potential use of higher doses of adintrevimab as needed to address emerging SARS-CoV-2 variants.

Disclosures
Xia Pu, PhD, Adagio Therapeutics: Employee|Adagio Therapeutics: Stocks/Bonds Jean Gong, PhD, Adagio Therapeutics: Employee|Adagio Therapeutics: Stocks/Bonds Ed Campanaro, BSN, MSHS, Adagio Therapeutics: Employee|Adagio Therapeutics: Stocks/Bonds Kristin Narayan, PhD, Adagio Therapeutics: Employee|Adagio Therapeutics: Stocks/Bonds Deepali Gupta, B.Sc, Adagio Therapeutics: Employee|Adagio Therapeutics: Stocks/Bonds Frank Engler, PhD, Adagio Therapeutics: Advisor/Consultant Amanda Copans, PharmD, Adagio Therapeutics: Employee|Adagio Therapeutics: Stocks/Bonds Pete Schmidt, MD, Adagio Therapeutics: Employee|Adagio Therapeutics: Stocks/Bonds.
227. Impact of Asymptomatic Bacteriuria on Primary Efficacy Analyses in the Evaluation of Novel Antimicrobials for the Treatment of Patients with Urinary Tract Infection
Authors: Aronin Steven I , Dunne Michael , Puttagunta Sailaja 
Published: December 2022

Abstract

Background
Per FDA Guidance, the primary efficacy endpoint for trials evaluating antimicrobials for treatment of uncomplicated urinary tract infection (uUTI) and complicated urinary tract infection (cUTI) is a combined clinical/microbiologic outcome response. Overall success requires both resolution of UTI symptoms and demonstration that the causative uropathogen is reduced to &lt; 103 CFU/mL at a fixed time point after randomization, regardless of whether the patient is symptomatic. In clinical practice, it is not standard of care to routinely screen for or treat asymptomatic bacteriuria (ASB), nor to obtain ‘proof of cure’ cultures. In the clinical trial setting, the impact of post-treatment asymptomatic bladder recolonization on the rates of microbiologic response, re-infection, or emergence of resistance is unknown.

Methods
Study IT001-301 and -302 are double blind, double-dummy, Phase 3 randomized trials comparing sulopenem to comparator for patients with pyuria, bacteriuria, and clinical signs/symptoms of uUTI and cUTI, respectively. In Study 301, 1671 ambulatory female adults with uUTI were randomized to oral sulopenem bid x 5d or oral ciprofloxacin bid x 3d. In Study 302, 1395 hospitalized adults with cUTI were randomized to sulopenem IV once daily x 5d followed by oral sulopenem bid or ertapenem IV once daily x 5d followed by either oral ciprofloxacin or amoxicillin-clavulanate bid, depending on baseline uropathogen susceptibility. The primary endpoint was overall (clinical + microbiologic) response in micro-MITT population at TOC visit (D12 in uUTI study and D21 in cUTI study).

Results
Figure 1

Conclusion
Different classes of antibiotics appear to have a differential effect on the frequency of post-treatment ASB with quinolones having a lower rate relative to beta-lactams. The presence of ASB a week or more after completing UTI therapy was not associated with a higher rate of clinical relapse for UTI patients; treatment with ciprofloxacin was associated with the selection of resistant pathogens in the post-treatment flora. Inclusion of ASB in the primary endpoint for studies of UTI should be reconsidered as it implies that a post-treatment culture should be obtained to document resolution of infection, a practice inconsistent with available treatment recommendations.

Disclosures
Steven I. Aronin, MD, Iterum Therapeutics: Stocks/Bonds Michael Dunne, MD, Iterum Therapeutics: Advisor/Consultant|Iterum Therapeutics: Board Member|Iterum Therapeutics: Stocks/Bonds Sailaja Puttagunta, MD, Iterum Therapeutics: Stocks/Bonds.
245. Can Inflammatory Markers be used as an Early predictor for Mechanical ventilation in COVID-19 patients with Stages IIIb-V Chronic Kidney Disease?
Authors: Geetha Harinivaas Shanmugavel , Gogtay Maya , Prabhu Sushmita , Sekar Abinesh , Singh Yuvaraj , Abraham George M , Martin Suzanne 
Published: December 2022

Abstract

Background
The clinical use of inflammatory markers soared during the COVID-19 pandemic. Though studies have shown C-reactive protein (CRP) to predict mechanical ventilation (MV) in patients with COVID-19, its utility is unknown in patients with chronic kidney disease (CKD), who have elevated baseline CRP levels due to chronic inflammation and reduced renal clearance of inflammatory cytokines. Our aim was to assess the association of inflammatory markers like CRP, ferritin, LDH, D dimer, and MV rate in patients with stages IIIb-V CKD and COVID-19.

Methods
We conducted a cross-sectional study on inpatients in a community hospital from 12/1/19 to 1/1/22 with COVID-19 and stages IIIb-V CKD without a previous renal transplant. Primary endpoints were invasive MV (IMV) rates, noninvasive MV (NIMV) rates, and no MV. Statistical analyses used unpaired t-test for continuous variables and chi-square analysis for categorical variables. Cutoffs for variables were CRP 100 mg/L, ferritin 530ng/ml, D-dimer 0.5mg/L and LDH 590 U/L. Univariate analysis and Area under curve (AUC-ROC) between the covariates and outcomes were computed.

Results
290 patients were screened, and 118 patients met inclusion criteria. CRP, D dimer, and ferritin were significantly different among the three groups. On univariate analysis for IMV, CRP had an OR 5.44; ferritin, OR 2.8; LDH, OR 7.7; D-dimer, OR 3.9, WBC count, OR 4.2 (p&lt; 0.05). Admission CRP level was 0.747 for the IMV group (AUC-ROC, sensitivity 80.8%, specificity 50%) and 0.663 for the NIMV group (AUC-ROC, sensitivity 69.2%, specificity 53%)

Conclusion
Our results illustrate a positive correlation between CRP, ferritin, and D-dimer levels and MV and NIMV rates. The ROC demonstrates a good sensitivity for CRP levels in detecting MV thereby emphasizing the utility of these biomarkers as good predictive markers in COVID-19 patients with CKD. With increasing use of inflammatory markers to prognosticate disease severity in COVID, the applicability of these markers in different populations should be investigated. A similar pattern of elevated inflammatory markers predicting the rate of MV was found in patients with stages IIIb-V CKD. This may be because of the greater magnitude of increased inflammation due to COVID-19 itself compared with increased inflammation due to CKD alone.

Disclosures
All Authors: No reported disclosures.
247. Catching CAPA: The Healthcare Impact of COVID-19-Associated Pulmonary Aspergillosis in an Academic Medical Center
Authors: Hamilton Caroline , Tran Sarah , Dinh Judy , Askar Gina , Askar Gina , Askar Gina , Askar Gina 
Published: December 2022

Abstract

Background
COVID-19 associated pulmonary aspergillosis (CAPA) is a known complication of COVID-19 which carries a high mortality rate. While there are proposed diagnostic criteria, CAPA remains likely underdiagnosed. Our objectives are to evaluate markers of disease severity, bacterial coinfections, and outcome measures in order to assess the clinical impact of CAPA in patients admitted with COVID-19.

Methods
A retrospective chart review was performed on all adult patients admitted to a single-center, tertiary hospital from March 1, 2020 to May 1, 2022 with a positive COVID-19 PCR and probable or proven CAPA based on ECMM/ISHAM consensus criteria. Admission data, ICU status, time to CAPA diagnosis, respiratory cultures, and 90-day mortality were identified.

Results
14 patients met criteria for probable CAPA. 10 of 14 patients (71.4%) were immediately admitted to the ICU. By day 14, 13 patients (92.9%) were intubated.
The average time from admission to CAPA diagnosis was 31.3 days. 12 patients were diagnosed by BAL galactomannan, while 2 patients were diagnosed by growth on respiratory culture. 12 patients (85.7%) also had bacterial growth on respiratory cultures. The most common pathogen was Staphylococcus aureus, which was seen in 6 patients.
All-cause mortality was 42.8%, or 6 of 14 patients, at day 90. In patients with a CAPA diagnosis, the average length of ICU stay was 36.4 days and average total hospital length of stay was 43.6 days, compared to 6.3 and 12.5 days, respectively, for all patients admitted with COVID-19 disease.

Conclusion
CAPA is a rare complication of COVID-19 but had substantial negative impacts on affected patients. The late onset of CAPA may be a result from longer hospitalizations and increased healthcare-associated infections. The association of CAPA with bacterial coinfections is consistent with literature on other viral infections such as influenza predisposing to secondary pneumonias. As the majority of cases were diagnosed by galactomannan rather than culture, providers should have a low threshold for testing in patients with protracted hospitalization for COVID-19. This case series emphasizes the poor outcomes associated with CAPA and its burden on already strained hospital resources, highlighting the need for improved disease awareness and further study.

Disclosures
All Authors: No reported disclosures.
250. Clinical Disease in Pediatric Long Covid
Authors: Wells Taylor , Gillen Sarah , Sharon Bazak 
Published: December 2022

Abstract

Background
Even weeks and months after initial infection, full recovery from a Covid-19 infection is elusive for some pediatric patients. Long Covid is now recognized as a chronic condition with a constellation of lingering health problems. As the long term sequala of Covid-19 continue to become apparent, it is imperative to study this emerging disease in the pediatric population.

Methods
The University of Minnesota Pediatric Covid Clinic has been receiving referrals since April 2020. The clinic is participating in a national registry (PIDTRAN-6_Covid-19), facilitating IRB approved collection of anonymized clinical data from children diagnosed with Long Covid syndrome.

Results
We have identified 47 children (female 28, male 19) who were diagnosed with Long Covid at the University of Minnesota Covid Clinic. The majority were previously healthy (40) and the average age was 14.7 years (4-18yr). Acute symptomatic infection preceded the diagnosis in 41 children and 6 children were asymptomatic. Common symptoms reported by the patients included: fatigue (35), dizziness and/or lightheadedness and/or palpitation (16), abnormal taste/smell (15), headache (14), difficulty concentrating/focusing [brain fog] (13), myalgia/arthralgia (15), dyspnea (12), abdominal pain (10), and sleep disturbance (6).
Clinical Symptoms of Long Covid
The nine most common clinical symptoms of Long Covid are shown in the chart above with the numbers corresponding to the number of patients who reported experiencing each symptom.
Demographics of Long Covid
The above graphic depicts the demographics of patients seen at the University of Minnesota Pediatric Long Covid Clinic.

Conclusion
Pediatric populations, like adult populations, have patients who suffer from the lingering health effects of what is now termed Long Covid. The majority of patients presenting with Long Covid are teenagers, with females being more commonly affected than males. These patients often suffer from fatigue and are experiencing a constellation of symptoms that are reminiscent of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and positional orthostatic tachycardia syndrome (POTS). This suggests a post-viral autoimmune injury as the likely pathophysiology for Long Covid syndrome. Further population based studies are needed to better understand the extent and prevalence of this debilitating disease.

Disclosures
All Authors: No reported disclosures.
255. Clinical, echocardiographic and electrocardiographic manifestations of COVID-19 multisystem inflammatory syndrome in children in the Dominican Republic
Authors: Roque Yori A , Luna David De , Mena Lora Alfredo J , Espinal Kelvin , Peralta Franzory , Maria Hilario 
Published: December 2022

Abstract

Background
The COVID-19 pandemic has spread globally and millions of infections have occurred. As cases mount, atypical manifestations of COVID-19 and post-infectious complications such as multisystem inflammatory syndrome in children (MIS-C) become more likely. MIS-C is a life threatening post-infectious complication of COVID-19. There is a paucity of data of MIS-C in the Dominican Republic (DR). We seek to understand the clinical manifestations of MISC-C in the DR.

Methods
This is a retrospective review of cases admitted to a pediatric hospital in the Dominican Republic from March 2020 to December 2021. Patients with clinical findings and a diagnosis of MIS-C were included. Echocardiographic (Echo) and electrocardiographic (ECG) changes were reviewed.

Results
A total of 16 patients were included in our study, of which 68.75 were male. Ages were 12.5% &lt; 1 years old, 12.5% between 1-4, 62.5% 5-12 and 12.5% over 12. Fever and rash were the most common clinical findings (Figure 1), while 69% had a new abnormality on echo and 50% had new ECG abnormalities. Echocardiographic findings are listed in Figure 2.
Clinical findings in patients admitted with MIS-C
Echo findings
ECG findings

Conclusion
The clinical manifestation of MIS-C are primarily fever, conjunctivitis, rash and hypotension. Because these findings can be non-specific, a high level of suspicion is needed. With over two thirds of patients with MIS-C showing echocardiographic changes and more than 50% showing ECG changes, these two tests can add significant diagnostic value in the right clinical setting. Clinicians should consider early echocardiography and ECG in patients with possible or suspected MIS-C.

Disclosures
All Authors: No reported disclosures.
258. Comparison of Different COVID Waves during COVID-19 Pandemic: A Retrospective Study from a Dedicated COVID-19 Facility of Karachi Pakistan
Authors: Sayeed Muneeba A 
Published: December 2022

Abstract

Background
In Pakistan, the first case of COVID-19 was reported in February2020. To date Pakistan has experienced 5 waves of COVID-19 and each COVID-19 wave is driven by a unique SARS CoV2 strain. In this study we have compared the clinical spectrum and outcome of different COVID-19 waves in a dedicated COVID-19 facility of Karachi.

Methods
We conducted a retrospective study at the Sindh Infectious Diseases Hospital and Research Centre (SIDH &RC), a 175 bedded dedicated first Infectious Diseases Hospital of Karachi, Pakistan. The hospital was established in July 2020. All patients &gt;16 years of age who were admitted with a positive COVID PCR from July 2020–Mar 2022 were included. First COVID wave in Pakistan lasted from Mar-July 2020, second wave from Oct 2020 to Jan 2021, third wave from Mar-May 2021, fourth from July to Sept 2021 while fifth from Jan 2022 to Mar 2022. Demographic and clinical data was collected of patients from each wave and analyzed by SPSS to compare the difference amongst different COVID waves. Chi-square and t-test were used for analysis.

Results
From July 2020-Mar 2022, 2900 COVID-19 patients were admitted. The total number of patients in each wave (from second to fifth waves) were 1217,783,590 and 310 respectively. The mean age in years was 60 in 2nd and 3rdwaves while it was 58 in 4th and 66 in 5th wave with 64.5%, 62.5%, 51.8%and 54% of males in each wave. On comparison majority 42% had moderate COVID in 2nd wave, 37% and 48.5% had severe COVID in 3rd and 4th waves respectively while the disease was mild (31%) in 5th wave (p-value of &lt; 0.001).Cytokine releasing syndrome (CRS) was common in 3rd wave (33%). Most intubations were done in 4thwave (21%). Compared to other waves mortality rate was also highest in 4thwave (35%, with p-valve of 0.03).

Conclusion
Based on our data fourth wave which was mostly driven by delta variant was the deadliest in terms of disease category and outcome.

Disclosures
All Authors: No reported disclosures.