bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of different obesity evaluation indexes on long-term blood pressure variability in adults
Authors: Huang R , Jing Z Q , Liu H Y , Li Z Y , Wu S S , Li D , Zhao F , Hao J , Yang C L , Song J S , Gu X Z
Published: November 2023

Background

In recent years, people have a new understanding of the treatment of hypertension. Even at the optimal blood pressure levels recommended by the guidelines, further attention to blood pressure variability is warranted. Obesity and overweight are associated with blood pressure variability, but existing studies mainly focus on the effect of traditional obesity indicators on blood pressure variability (BPV).

Objectives

To explore the correlation between the new obesity assessment indicators LAP, BRI, CVAI and blood pressure variability.

Methods

A total of 7092 subjects who had regular physical examination in a community health center, were included for analysis. We used new measures to assess obesity, including LAP, BRI, CVAI. Subjects were grouped according to the baseline CVAI quartile. We used variation independent of mean(VIM) to assess long-term variations in blood pressure. Variance analysis was used to analyze the differences among different blood pressure variables and their baseline characteristics. Stepwise multivariate linear regression and multiple logistic regression analyses were used to assess the impact of CVAI/LAP/BRI on VIM.

Results

The average age of the subjects was 60.7±6.8 years old. With the increase of CVAI and BRI, the mean blood pressure variability increased gradually. In contrast, the mean blood pressure variability decreases with increasing LAP. After adjusting for other confounding factors, multiple linear regression analysis showed that VIMSBP increased by 0.007 and 0.216 for each unit increase in CVAI and BRI, respectively. LAP found no correlation. Multiple logistic regression analysis showed that increased CVAI and BRI were risk factors for increased VIMSBP, and increased LAP was protective factor for increased VIMSBP.

Conclusion

Compared with traditional indicators, the novel obesity indicators were also associated with blood pressure variability. And it has a stronger correlation than traditional indicators.
Practice guidelines for cardiovascular disease: how is depression addressed?
Authors: Blatch Armon D , Buhayer A , Dobretz K , Mach F , Meinlschmidt G , Battegay E
Published: November 2023

Introduction

Multimorbidity is associated with increased mortality, decreased quality of life, and increased use of healthcare services and complicates medical decision-making. Depression is more prevalent among patients with CVD than in the general population, with a direct impact on cardiovascular outcomes and management. Clinical practice guidelines (CPGs) aim to provide the best available advice for improving patient care and outcomes.

Question: Do CPGs on CVD provide any practical guidance on depression screening and management?

Methods

National and international CPGs on CVD prevention and management published between 2012 and 2023. English language only. Databases: MEDLINE n=2432. EMBASE n=327; G.I.N. n=57; Guideline Central: n=97; Uptodate n=26; Society homepages (e.g. NICE, SIGN) n=7. Selection criteria: general management guidelines for adult patients diagnosed with a CVD, as well as disease-specific CPGs (e.g. heart failure (HF), coronary artery disease, peripheral arterial disease (PAD), ischaemic disease, stroke or hypertension (HT)) providing patient-management guidance. Eligible guidelines: evaluated for any mention of depression, with a focus on: 1) recommendations regarding depression screening and treatment; 2) drug-drug or drug-disease interactions associated with depression.

Results

43 CVD CPGs provide comprehensive management advice: 7 from CVD in general and 36 from specific disease in CVD (11 from HT, 7 from ischemic heart disease, 7 from HF, 5 from dyslipidemia, 3 from stroke, and 3 from PAD). 26 CVD CPGs mention depression as a CV comorbidity at least once: 22 in specific disease CPG and 4 in general CVD CPGs. 15 CVD CPGs advise to screen for depression: 4 from CVD in general and 11 from specific disease in CVD (4 from ischemic heart disease, 3 from HF, 2 from HT, 1 from PAD, and 1 from stroke). 8 CVD clinical practice guidelines provide advice on management of depression: 3 from CVD in general and 5 from specific disease (2 from HT, 2 from ischemic heart disease and 1 from HF). 4 CVD clinical practice guidelines advise on drug-drug or drug-disease interactions. When provided, the level and quality of guidance for treating physicians on how to screen and manage depression remains very low.

Conclusion

Management of CVD in the specific clinical setting of depression remains poorly addressed, despite it being documented that factors associated with poor adherence to CVD treatment include depression.

Future directions: The psychosocial needs of patients with CVD should be systematically assessed and addressed in an evidence-based manner. There is a need for clear practical guidance on the frequency at which a patient’s mental health should be reassessed. Patient panels can help provide practical information toward addressing depression in the development of guidelines.The AIDS CPG address depression in detail and could serve as a model for future CVD CPGs.
Impact of atrial fibrillation type on outcomes following aerobic exercise training: analysis from the ACTIVE-AF Trial
Authors: Elliott A , Verdicchio C V , Mahajan R , Gallagher C , Lau D H , Middeldorp M E , Sanders P
Published: November 2023

Background

The ACTIVE-AF study demonstrated that aerobic exercise prescription promotes the maintenance of sinus rhythm in patients with atrial fibrillation (AF). However, it is unclear whether these benefits are observed in patients with both paroxysmal and persistent AF.

Purpose

Compare efficacy of exercise intervention on arrhythmia recurrence between paroxysmal (ParAF) and persistent (PerAF) patients.

Methods

This study was a prospective, randomized, controlled trial of patients with symptomatic paroxysmal or persistent AF, referred for consideration of AF ablation. Randomization was 1:1 to either aerobic exercise intervention or usual medical care for a period of 6 months with a further 6 months follow-up. The exercise intervention was delivered in a hybrid format of weekly supervised exercise sessions coupled with prescribed home exercise, up to a total of 210 minutes per week. The intervention was led by a clinical exercise physiologist. Management of arrhythmia was at the discretion of a cardiologist blinded to patient randomisation. The primary endpoint reported here is recurrent AF without rhythm control strategies.

Results

Of the 120 patients enrolled in the study, 74 (62%) had a history of ParAF. Patients with PerAF typically had higher body mass index (32.0±6.6 versus 29.5±5.2 Kg/m2, p=0.02) and left atrial volume (38.0±9.4 versus 28.1±6.5 mL/m2, p<0.001) but similar prevalence of hypertension, diabetes mellitus, coronary artery disease and obstructive sleep apnea. Baseline peak oxygen consumption (VO2peak) was similar between ParAF and PerAF groups (20.0±6.0 versus 19.6±5.4mL/kg/min). Over the 12-month follow-up, AF recurrence in the ParAF patients was lower in the exercise group compared to control group (Hazard Ratio 0.42, 95% CI: 0.23-0.77, p=0.005). However, we did not find evidence of any between-group difference amongst patients with PerAF (HR 0.65, 95% CI: 0.34-1.23).

Conclusions

In this post-hoc analysis of a randomised controlled trial comparing the efficacy of exercise intervention versus standard medical care amongst patients with symptomatic AF, we observed a reduction in AF recurrence for patients with ParAF, but not amongst those with PerAF. These findings support the need for early lifestyle modification amongst patients with AF, before progression to PerAF occurs. Future studies should explore whether the exercise prescription can be modified to improve outcomes for patients with more advanced AF.
HDLc levels have a protective effect for in-hospital mortality in Non-STEMI but not in STEMI patients
Authors: Cordero A , Badimon L , Alvarez-Alvarez B , Rodriguez-Manero M , Seijas-Amigo J , Escribano D , Lopez-Ayala J M , Vilahur G , Garcia-Acuna J M , Gonzalez-Juanatey J R
Published: November 2023

Background

High-density lipoprotein cholesterol (HDLc) has been associated to lower myocardial infarction size although it is not considered a primary target in cardiovascular prevention or as treatment target in patients with cardiovascular disease. The role of HDLc on in-hospital mortality in acute coronary syndrome (ACS) patients could be influenced by many variables.

Methods

We performed and observational and cross-sectional analysis of all patients admitted for an ACS in 2 tertiary hospitals in Spain between 2006 and 2016. HDL was measured in the first 24 of the admission in the first overnight fasting state.

Results

We included 8,684 patients, mean (standard deviation) age 66.88 (12.90), 27.5% women, mean GRACE score 143.13 (40.27), and 35.09% admitted for ST-elevation myocardial infarction (STEMI). Mean HDLc levels were 35.90 (13.64) mg/dL in whole cohort and were significantly lower in patients presenting as non-STEMI (35.53±13.62 vs. 36.55± 13.65 mg/dL), those with GRACE score <140 (35.09±13.00 vs. 36.78±14.24 mg/dL) and women (34.28±12.81 vs. 40.21±14.80 mg/dL) but not in patients who died or not (p=0.43). From these variables, we observed a significant interaction of HDLc levels and STEMI presentation (p=0.03) for in-hospital mortality risk and, thus, results were analyzed separately.

After natural logarithm transformation, in-hospital mortality risk had a "U-shaped" distribution in STEMI patients compared to the linear trend in Non-STEMI patients (figure 1). Multivariate analysis, adjusted by age, gender, risk factors, hemoglobin, revascularization and GRACE score, verified the interaction and the protective effect of HDLc in Non-STEMI patients (OR: 0.48 95% CI 0.28-0.80; p=0.005) but not in STEMI patients (OR: 0.96 95% CI 0.55-1.67; p=0.887) (figure 2).

Conclusions

Clinical presentation of STEMI vs. non-STEMI modifies the effect of HDLc on in-hospital mortality. HDLc might have a protective effect in patients presenting with non-STEMI only.
Longitudinal trajectories of lipid parameters and their associations with mid-life carotid intima-media thickness
Authors: Kohansal K , Abdi A M I R , Afaghi S I A M A K , Hadaegh F A R Z A D , Khalili D A V O O D
Published: November 2023

Background/Introduction

Studies showed positive associations between previous dyslipidemia and subsequent subclinical atherosclerosis.

Purpose

To examine the longitudinal association of cumulative burden of different lipid parameters and subsequent carotid intima-media thickness (CIMT).

Methods

Using data from the Coronary Artery Risk Development in Young Adults (CARDIA) study from year 0 (Y0) to year 20 (Y20), young adulthood, midlife, and also longitudinal cumulative burdens (estimated by the area under the curve (AUC) using nonlinear mixed-effects methods) values of different lipid parameters including TC, LDL-C, non-HDL-C, HDL-C, Remnant-C, and Ln TG were considered as exposures. Linear regression models were used to estimate the effect of each 1-SD change in exposure variables on mean CIMT by sex-race group.

Results

In 2991 black and white women and men participants, young adulthood, midlife, and cumulative burden of TC, LDL, and non-HDL were associated with the increased mean of CIMT in black and white and also men and women populations; higher impacts were founded in whites compared to blacks and men compared to women for young adulthood and cumulative burden values (all p for interactions <0.05). In terms of other lipid parameters, in women and whites, longitudinal increases in Remnant-C and Ln-TG cumulative burdens were associated with increased mean CIMT, whereas increases in HDL-C cumulative burdens were associated with decreased mean CIMT.

Conclusions

Midlife to later-life cumulative burdens of different lipid parameters are associated with mean CIMT which these associations are different between races and genders.12
Strike Cover, Consultation and Quashing: An Analysis of R. (Associated Society of Locomotive Engineers and Firemen) v Secretary of State
Authors: Bell Joanna
Published: November 2023

In June 2022, the UK Government enacted Regulations purporting to remove the offence of introducing or supplying workers to cover those on strike. In R. (Associated Society of Locomotive Engineers and Firemen) v Secretary of State the High Court held that the decision-making process preceding the enactment of the Regulations was unlawful and quashed them. This analysis outlines the case, with a particular focus on the central role played by the existence of a statutory duty to consult in the court's reasoning and the extent to which third party interests were considered in the course of determining the proper remedy.
Role of the integrin-linked kinase/TGF-β/SMAD pathway in sitagliptin-mediated cardioprotective effects in a rat model of diabetic cardiomyopathy
Authors: Bin Dayel Anfal F , Alonazi Asma S , Alrasheed Nawal M , Alamin Maha A , Sarawi Wedad S , Alharbi Abeer O , Alabbad Nahla’a A , Albuaijan Danah A , Alassiri Dareen N , Aljarbua Alanoud F , Almusaytir Fatimah K , Alrasheed Nouf M
Published: November 2023

Objectives

Diabetic cardiomyopathy is a known complication of diabetes mellitus. Herein, we aimed to determine whether glycemic control mediated by sitagliptin, a dipeptidyl peptidase-4 inhibitor, can ameliorate diabetic myocardial abnormalities by modulating TGF-β signaling via the SMAD and integrin-linked kinase (ILK) pathways.

Methods

Four groups of male Wistar albino rats were used, with six rats in each group. Two nondiabetic and two diabetic (produced by a single intraperitoneal dose of streptozotocin (55 mg/kg)) groups were administered either normal saline or sitagliptin (100 mg/kg) orally for 6 weeks. Subsequently, HW/BW ratios and cardiac enzymes were assessed, along with a histological examination of cardiac tissues. Levels of TGF-β, collagen I, p-SMAD2/3, TNF-α, MMP-9, and ILK were detected.

Results

Compared with the diabetic control group, sitagliptin-treated diabetic rats exhibited considerably reduced HW/BW ratios and troponin I and creatine kinase-MB levels, with improvements in histopathological changes in cardiac tissues. TGF-β, collagen I, p-SMAD2/3, TNF-α, and MMP-9 levels were significantly decreased in the sitagliptin-treated diabetic group, whereas ILK was elevated following sitagliptin treatment.

Conclusion

Sitagliptin could afford cardioprotective effects for the first time by altering ILK-associated TGF-β/SMAD signaling pathways. Thus, sitagliptin may be a promising therapeutic target for the prevention of diabetic cardiomyopathy.
MATLAB-Based Algorithm and Software for Analysis of Wavy Collagen Fibers
Authors: Polzer Stanislav , Thompson Sarah , Vittalbabu Swathi , Ulu Arzu , Carter David , Nordgren Tara , Eskandari Mona
Published: November 2023

Knowledge of soft tissue fiber structure is necessary for accurate characterization and modeling of their mechanical response. Fiber configuration and structure informs both our understanding of healthy tissue physiology and of pathological processes resulting from diseased states. This study develops an automatic algorithm to simultaneously estimate fiber global orientation, abundance, and waviness in an investigated image. To our best knowledge, this is the first validated algorithm which can reliably separate fiber waviness from its global orientation for considerably wavy fibers. This is much needed feature for biological tissue characterization. The algorithm is based on incremental movement of local regions of interest (ROI) and analyzes two-dimensional images. Pixels belonging to the fiber are identified in the ROI, and ROI movement is determined according to local orientation of fiber within the ROI. The algorithm is validated with artificial images and ten images of porcine trachea containing wavy fibers. In each image, 80–120 fibers were tracked manually to serve as verification. The coefficient of determination R2 between curve lengths and histograms documenting the fiber waviness and global orientation were used as metrics for analysis. Verification-confirmed results were independent of image rotation and degree of fiber waviness, with curve length accuracy demonstrated to be below 1% of fiber curved length. Validation-confirmed median and interquartile range of R2, respectively, were 0.90 and 0.05 for curved length, 0.92 and 0.07 for waviness, and 0.96 and 0.04 for global orientation histograms. Software constructed from the proposed algorithm was able to track one fiber in about 1.1 s using a typical office computer. The proposed algorithm can reliably and accurately estimate fiber waviness, curve length, and global orientation simultaneously, moving beyond the limitations of prior methods.
Connecting core galaxy properties to the massive black hole binary population
Authors: Harris C J , Gültekin Kayhan
Published: November 2023

We investigate how the properties of massive black hole binaries influence the observed properties of core galaxies. We compare the observed trend in stellar mass deficit as a function of total stellar mass in the core galaxy with predicted trends in IllustrisTNG. We calculate mass deficits in simulated galaxies by applying subgrid, post-processing physics based on the results of literature N-body experiments. We find that the median value of the posterior distribution for the minimum binary mass ratio capable of creating a core is 0.7. For the gas mass fraction above which a core is erased, we find a median value of 0.6. Thus, low mass ratio binaries do not contribute to core formation and gas-rich mergers must lead to star formation within the nucleus, ultimately erasing the core. Such constraints have important implications for the overall massive black hole binary population, black hole–galaxy co-evolution, and the origin of the gravitational wave background.
Black hole binary mergers in dense star clusters: the importance of primordial binaries
Authors: Barber Jordan , Chattopadhyay Debatri , Antonini Fabio
Published: November 2023

Dense stellar clusters are expected to house the ideal conditions for binary black hole (BBH) formation, both through binary stellar evolution and through dynamical encounters. We use theoretical arguments as well as N-body simulations to make predictions for the evolution of BBHs formed through stellar evolution inside clusters from the cluster birth (which we term primordial binaries), and for the sub-population of merging BBHs. We identify three key populations: (i) BBHs that form in the cluster, and merge before experiencing any strong dynamical interaction; (ii) binaries that are ejected from the cluster after only one dynamical interaction; and (iii) BBHs that experience more than one strong interaction inside the cluster. We find that populations (i) and (ii) are the dominant source of all BBH mergers formed in clusters with escape velocity vesc ≤ 30 $\mathrm{km\, s^{-1}}$. At higher escape velocities, dynamics are predicted to play a major role both for the formation and subsequent evolution of BBHs. Finally, we argue that for sub-Solar metallicity clusters with vesc ≲ 100 $\mathrm{km\, s^{-1}}$, the dominant form of interaction experienced by primordial BBHs (BBHs formed from primordial binaries) within the cluster is with other BBHs. The complexity of these binary–binary interactions will complicate the future evolution of the BBH and influence the total number of mergers produced.
88. Fostamatinib for the Treatment of Hospitalized Patients With COVID-19 Who Required Oxygen Supplementation: Results of a Phase 3 Trial
Authors: Gotur Deepa B , Malik Anuj , Markovtsov Vadim , Yan Lucy , Dummer Wolfgang , Mallat Ziad
Published: November 2023

Background

Severe COVID-19 is linked to hyperactivation of the host immune response involving signaling through multiple spleen tyrosine kinase (SYK) pathways. Fostamatinib is an orally administered potent and selective inhibitor of SYK that has been approved in the US, Canada, Japan, and Europe for the treatment of chronic immune thrombocytopenia (ITP).

Methods

We conducted a double-blind, randomized, placebo-controlled phase 3 trial of fostamatinib in adults hospitalized for COVID-19 who required oxygen supplementation (NCT04629703). Patients (pts) were randomly assigned 1:1 to receive fostamatinib (150 mg BID administered orally) or placebo for 14 days. All pts additionally received standard of care at their hospital. The primary endpoint was days on oxygen (days 1-29).

Results

A total of 280 pts underwent randomization (with 141 assigned to fostamatinib and 139 to placebo). The primary endpoint was met; those who received fostamatinib had lower mean days on oxygen than those who received placebo (4.8 vs. 7.6 days, P=0.0136; Table 1).

Fostamatinib showed significance or trend towards significance in all secondary endpoints of reducing mortality and morbidity compared to placebo. The mean change in the 8-point ordinal score from baseline to the average of Day 5 to 15 was significantly improved in pts who received fostamatinib vs. placebo (P=0.0092,Table 1). Furthermore, 6 pts were enrolled with a baseline ordinal score of 6 (3 in each group). All patients in the fostamatinib group survived, and all in the placebo group died by Day 30. A significantly higher proportion of pts who received fostamatinib were discharged from the hospital by Day 15 compared to placebo (P=0.0029,Table 1). Significantly more patients were alive and oxygen-free by Day 29 and Day 60 with fostamatinib treatment in comparison to placebo (P=0.0213 and P=0.0271, respectively, Table 1). Treatment-emergent adverse events were consistent with previous studies and were similar between the 2 groups.

Conclusion

The addition of fostamatinib to standard of care treatment resulted in significantly fewer days on oxygen, an improved 8-point ordinal scale score, and significantly more patients alive and oxygen-free by Day 60 compared to placebo in pts with COVID-19 requiring hospitalization and supplemental oxygen.

Disclosures

Deepa B. Gotur, MD, FCCP, FCCM, GSK: Advisor/Consultant|GSK: Speaker at ATS|Moderna: Advisor/Consultant Vadim Markovtsov, PhD, Rigel Pharmaceuticals, Inc.: Employee|Rigel Pharmaceuticals, Inc.: Stocks/Bonds Lucy Yan, MD, PhD, Rigel Pharmaceuticals, Inc.: Employee|Rigel Pharmaceuticals, Inc.: Stocks/Bonds Wolfgang Dummer, MD, PhD, Rigel Pharmaceuticals, Inc.: Stocks/Bonds.
98. Resurgence of Invasive Group A Streptococcal Disease in Utah Children
Authors: McMillion Benjamin , Pershing Nicole L , Crandall Hillary , Krow Ampofo Kwabena , Hersh Adam , Olson Jared , Oakeson Kelly F , Wagner Jennifer M , Young Erin L , Nielsen Shannon , Dickey Mandy , Huynh Kelly , Pavia Andrew T , Blaschke Anne J
Published: November 2023

Background

Streptococcus pyogenes (GAS) is a common cause of non-invasive mucosal infections in childhood as well as life-threatening invasive infections. Since 1997, emm1 has been the most common emm type associated with invasive GAS (iGAS) in the US. Apparent increases in iGAS have been reported in several countries during the winter of 2022-23. We sought to characterize changing clinical and molecular epidemiology of iGAS disease in Utah children before and after the emergence of COVID-19.

Methods

We retrospectively identified children 0-18 years with iGAS treated at Primary Children’s Hospital (Salt Lake City, Utah) from 2018- 2023. Cases were identified through the laboratory database. Electronic health record review confirmed that cases met the CDC definition of iGAS and streptococcal toxic shock syndrome (STSS). We abstracted demographics, disease classification and outcomes (Table). Comparisons were made across years. GAS isolates underwent whole genome sequencing for emm type determination.   

Results

From 1/2018 to 3/2023, we identified 141 cases of iGAS. Case numbers ranged from 6/yr (2021) to 39 (2019). The highest number of cases by quarter was seen in Q1 2023 (Figure). We observed a marked decrease in iGAS from Q1 2020 through Q3 2022 followed by a steep increase, coinciding with surges in RSV and influenza. Demographics were similar across the study period. 60% of iGAS cases were in males. Complicated pneumonia and head/neck infections predominated. iGAS associated with STSS appeared higher post-pandemic (4/73 [5%] cases in 2018-19 vs. 8/51 [16%] in 2022-23 [OR = 3.2; 95% CI 0.8-15]). The majority of STSS (7/12; 57%) was associated with complicated pneumonia. Clinical outcomes were comparable pre- and post-pandemic. emm types were available for 49/51 (96%) of isolates in 2022-23. emm1 and emm12 were associated with 67% of iGAS disease (emm1 n = 16 [33%]; emm12 n = 17 [35%]).

Conclusion

After a marked drop in iGAS infections in children during the COVID-19 pandemic in Utah there was a resurgence of iGAS starting in late 2022 and early 2023, modestly exceeding pre-pandemic levels. emm1 and emm12 predominated in the surge. Further analysis of disease severity and molecular epidemiology are in progress. 

Disclosures

Kwabena Krow Ampofo, MD, Merck: Advisor/Consultant|Merck: Grant/Research Support Andrew T. Pavia, MD, GlaxoSmith Kline: Advisor/Consultant|Sanofi: Advisor/Consultant Anne J. Blaschke, MD, PhD, BioFire Diagnostics: Grant/Research Support|BioFire Diagnostics: I have IP owned by the U. of Utah licensed to BioFire and receive royalties. I have been a consultant and received grant support as well.|Merck and Company, Inc.: Advisor/Consultant
101. Serious Adverse Event Rates for Cefazolin and Ceftriaxone Outpatient Parenteral Antimicrobial Therapy
Authors: Sunagawa Shawnalyn , Arduser Sarah , Miller Molly M , Lyden Elizabeth , Cortes-Penfield Nicolas W , Hankins Richard , Bergman Scott J , Alexander Bryan T
Published: November 2023

Background

Beta-lactams are thought to be well-tolerated in outpatient parenteral antimicrobial therapy (OPAT), but few studies address the utility of regularly monitoring laboratory parameters for beta-lactams in the OPAT setting. Our aim was to assess OPAT adverse event (AE) rates for cefazolin and ceftriaxone to better define appropriate laboratory monitoring for these antimicrobials.

Methods

We retrospectively evaluated patients prescribed either cefazolin or ceftriaxone via OPAT between 3/1/2019-9/30/2022. Combination intravenous antimicrobial therapies were excluded. The primary outcome was incidence of clinically significant OPAT-related AEs, defined as drug-related AE leading to treatment alterations (e.g., abnormal labs, allergic reactions, Clostridioides difficile infection) or any catheter-associated AE. Secondary outcomes included time from start of therapy to clinically significant AEs, unplanned healthcare utilization (e.g., emergency department visits, readmissions), and factors associated with increased risk of clinically significant AEs. We performed descriptive statistics for cohort characteristics, Fisher’s exact and independent sample T-tests for associations with primary and secondary outcomes, and univariate and multivariate regressions for predictors of AEs.

Results

Characteristics of the cohort are listed in Table 1. Primary and secondary outcomes are reported in Table 2. There were 3282 sets of weekly labs, 99.7% were obtained and reviewed within 72 hours from lab draw. Laboratory monitoring detected 2.7 clinically significant AEs per 1000 sets of weekly labs. Median time from start of therapy to abnormal lab drug-associated AE was 26 days (IQR 19, 34). Univariate and multivariate logistic regressions are listed in Table 3. There were no statistically significant differences in antibiotic, duration of therapy, or OPAT modality between the groups with or without clinically significant drug-related AE.

Conclusion

Cefazolin and ceftriaxone were well tolerated during OPAT, with few drug-associated AEs mainly occurring beyond 3 weeks of therapy. As we identified just 2.7 clinically significant AEs per 1000 sets of weekly labs, routine weekly laboratory monitoring for cefazolin and ceftriaxone in the OPAT setting may be excessive.

Disclosures

Scott J. Bergman, PharmD, bioMerieux, Inc.: Honoraria Bryan T. Alexander, PharmD, BCIDP, AAHIVP, Astellas Pharma: Advisor/Consultant|F2G: Advisor/Consultant|Merck: Grant/Research Support
961. Prevalence of Surgical Site Infections and Bacteremia in Pediatric Patients Receiving Extracorporeal Membrane Oxygentaion
Authors: Siraj Althagafi Samiyah , Abdullah Alsuhaibani Mohammed , Murdhi Alenzi Mashael , Abdulrahaman Alyabes Ohoud , Mohammed Beheri Reem , Khalid Alrawaf Fahad , Abdullah Almalki Afnan , Tariq Alhuthil Raghad
Published: November 2023

Background

Extracorporeal membrane oxygenation (ECMO) is a well-known type of advanced life support used in critically ill patients with serious heart and/or lung problems. ECMO treatment is associated with multiple life-threatening complications. The objectives of this study were to identify the prevalence of surgical site infections (SSI) and bloodstream infections (BSI) along with the associated risk factors and outcomes in patients on ECMO.

Methods

In this retrospective study, clinical charts of patients were reviewed from January 2012 to April 2023. All admitted pediatric patients 14 years or less who received ECMO treatment were enrolled. Mann-Whitney and Fisher exact tests were used to assess mortality-related risk factors.

Results

A total of 165 patients were included in the study, 79 (47.88%) females and 86 (52.12%) males, with a median age of 4 [IQR 0.8-24] months. BSI were found in 33 (20%) of them, 10 (30.30%) were gram-positive, 25 (75.75%) were gram-negative, and 6 (18.18%) were fungi. Furthermore, 33 (20%) developed SSI. The overall mortality rate in this study is (50.30%) with a median duration from ECMO procedure initiation to death being 11 [IQR: 5-26] days. Most of mortalities (78.31%) were noticed in infants aged ≤24 months. Compared with patient with neither SSI nor BSI, patients with SSI and BSI had a higher mortality rates of 19 (22.89%) and 16 (19.28%) respectively.

Additionally, other noted complications were mediastinitis 4 (2.42%), sternal osteomyelitis 2 (1.21%), infective endocarditis 4 (2.42%).

Younger age and thrombocytopenia were found to be a mortality related risk factors (P value 0.04 and 0.01 respectively).

Conclusion

Our study found a high rate of bacteremia and SSI in pediatric patients receiving ECMO. Younger age, thrombocytopenia were the potential risk factors associated with higher mortality rates in this group.

Disclosures

All Authors: No reported disclosures
987. Identification of Fungal Pathogens In Formalin-Fixed Paraffin-Embedded (FFPE) Tissues by Targeted Next-Generation Sequencing (NGS) Technology
Authors: Totten Marissa C , Morris Christopher P , Ariyaratne Pramila , Zhang Tony , Zhang Sean , Lee Charlie
Published: November 2023

Background

Histological presence of fungal organisms associated with tissue damage is the hallmark for invasive fungal diseases. Rapid and accurate identification (ID) of these fungal pathogens present is critical for initiating appropriate treatment without delay. We investigated an automated sample-to-answer targeted NGS workflow for the ID of fungi directly from FFPE tissues.

Methods

170 FFPE tissues (93 cases) from 2002 to 2022 at Johns Hopkins Hospital were selected based on histologic findings of the presence of fungal pathogens. Samples were run by PathoKey SQ Flex assay, (Vela Diagnostics) which includes automated extraction, library preparation and emulsion PCR followed by NGS on a Sentosa SQ301 and analyzed using Vela’s curated database. Two negative controls (NCs) were included on each run. To compare NGS results, 51 samples were extracted using the MagMAX™ FFPE DNA/RNA Ultra Kit (Applied Biosystems) followed by pan-fungal PCR (ITS1/ITS2/D1D2) and Sanger sequencing (SS) and analyzed through NCBI nucleotide blast for ID.

Results

116/170 (68%) samples had culture results: 69/116 (59%) were concordant with Vela NGS (VS) ID to the genus/species level; 18/28 (64%) samples were concordant with SS ID to the genus/species level. Among 54 samples with no/negative culture results: 26/54 (48%) were presumptive Mucorales, of which 23/26 (88.5%) were supported by VS ID and 5/12 (42%) supported by SS ID; 12/54 (22%) were presumptive aspergillus-like hyphae fungi, of which 10/12 (83%) were supported by VS ID and 4/9 (44%) supported by SS ID. 15/170 (8.8%) samples had no VS ID due to QC failures, and 15/26 (58%) with no VS ID had no organism seen or scant amount of fungal load in the histology slide.

Conclusion

VS detected fungal organisms in 76% (129/170) of FFPE tissues, of which it correctly ID-ed pathogens down to the genus/species level in 94% (102/129) of samples. VS is more sensitive to pathogen ID than SS. Samples with discordant or no results by VS were mostly due to small tissue input or low fungal loads present in histology. Environmental or human skin flora contamination reads overshadowing possible pathogens were observed in few cases; therefore, it is critical to include NCs in each run to distinguish them from clinically significant fungal pathogens.

Disclosures

Marissa C. Totten, MA, Vela Diagnostics: Grant/Research Support Pramila Ariyaratne, n/a, Vela Diagnostics: Employee Tony Zhang, n/a, Vela Diagnostics: Employee Sean Zhang, MD, PhD, Applied BioCode: Grant/Research Support|IMMY Diagnostics: Grant/Research Support|KARIUS: Advisor/Consultant|Pearl Diagnostics: Grant/Research Support|Scanogen: Grant/Research Support|T2 biosystems: Advisor/Consultant|Vela Diagnostics: Grant/Research Support Charlie Lee, Ph.D, Vela Diagnostics: Employee
1021. Semi-nested Molecular Method for the Diagnosis of Invasive Fungal Infections in Combat Injured
Authors: Ellis Graham C , Shaikh Faraz , Carson M Leigh , Sercy Erica , Stewart Laveta , Andrews Jared M , Campbell Wesley , Mende Katrin , Yabes Joseph , Bialek Ralf , Tribble David R , Wickes Brian , Ganesan Anuradha
Published: November 2023

Background

Among combat injured, invasive fungal infections (IFI) result in significant morbidity (eg surgical amputations). Primary diagnostic methods are limited as cultures are insensitive and time delayed, and histopathology often cannot provide genus level identification needed for directed treatment. We previously evaluated a panfungal PCR (PF) assay and it was 83% sensitive and 99% specific for angioinvasive IFI (AIFI). The PF assay requires substantial expertise and cannot be easily performed at all facilities. Thus, we evaluated less resource intensive semi-nested PCR (SN) targeted to clinically relevant fungi (order Mucorales and genus Aspergillus and Fusarium).

Methods

Formalin-fixed paraffin-embedded tissue (FFPE) specimens from a multicenter trauma IFI cohort (2009-14) were used. Cases were US military personnel injured in Afghanistan with histopathologic IFI evidence. Controls were patients with similar injury patterns and no laboratory IFI evidence (negative culture and histopathology). SN assays specific to Mucorales (V4/V5 regions of 18S rDNA), Aspergillus (P2/Asp2 regions of mitochondrial tRNA), and Fusarium (internal transcribed spacer [ITS]/28A regions of DNA) were compared to a PF assay amplifying the ITS2 region of rDNA and to histopathology. Performance characteristics and Cohen’s Kappa coefficients were calculated.

Results

Specimens from 92 injury sites (62 subjects) were compared to control specimens from 117 injuries (101 subjects; Fig 1). We observed substantial agreement between SN and PF assays overall and for order Mucorales (Table 1). Moderate agreement was observed at the genus level for Aspergillus and Fusarium. When compared with histopathology, sensitivity and specificity of SN assays were 64.7% and 96.6% respectively (91.7% and 96.6% when restricted to AIFI; Table 2). No statistically significant difference in performance between the SN and PF assays was observed.

Conclusion

Prior studies of SN molecular diagnostics have focused on culture-negative samples from immunocompromised patients. Our findings underscore utility of the SN approach in diagnosing IFI using FFPE samples, especially AIFI. Given the known DNA degradation with formalin fixation, sensitivity of SN assays may be higher in unfixed specimens and should be examined.

Disclosures

All Authors: No reported disclosures
1102. Pediatric Hepatitis C Screening by Maternal Hepatitis C Viral Load Status in Pregnancy
Authors: DiNicola Julia , Chappell Catherine , Rick Anne-Marie
Published: November 2023

Background

The rise of hepatitis C (HCV) infections among reproductive-age women increases the number of infants at risk for perinatal HCV infection, but screening remains low. It is unknown if maternal HCV viral load (VL) during pregnancy influences infant screening practices.

Methods

Using an existing retrospective cohort of mother-infant pairs with longitudinal well-child care from a single healthcare system, we included infants born from 2015 to 2019 with perinatal HCV exposure based on maternal or infant HCV-specific ICD diagnosis codes and/or laboratory testing and confirmed by reviewing electronic health records. Maternal HCV VL during pregnancy was classified as positive (+), negative (-) or unknown based on HCV RNA testing (or lack-thereof) obtained between 12 months before to 3 months after the infant’s birth date. Adequate infant screening included an HCV RNA test obtained ≥ 2 months of age or an HCV antibody test ≥ 12 months of age. We used univariate logistic regression to compare odds of infant screening based on maternal HCV VL during pregnancy.

Results

Of the 501 HCV-exposed infants, 139 (28%) were born to HCV+/VL- women, 100 (20%) to HCV+/VL unknown women, and 262 (52%) to HCV+/VL+ women. The proportion of screening tests ordered ranged from 68-82%, while test completion ranged from 64-70% (Figure 1). Overall, screening for HCV varied by maternal HCV VL (43% (60/139) HCV+/VL-; 50% (50/100) HCV+/VL unknown; 58% (152/262) HCV+/VL+). Perinatal HCV ranged from 1.7-6% depending on maternal HCV VL status (Figure 1). Infants born to HCV+/VL+ women were two times more likely to have a screening order compared to infants of HCV+/VL- women; but there was no difference for infants of HCV+/VL unknown women (Table 1). Among those with tests ordered, there was no difference in completion between groups (Table 1).Figure 1.Flow Diagram of Perinatal Hepatitis C Screening of Infants Exposed to Hepatitis C in utero.

Conclusion

Although infants born to HCV+/VL+ women are more likely to be screened for HCV, many, regardless of maternal HCV VL during pregnancy, are never adequately screened and pediatric HCV infections are going undetected. Efforts to increase caregiver and clinician awareness of infant HCV screening guidelines, including consideration of earlier RNA or office-based HCV screening, may improve screening rates and detection of HCV infected infants.

Disclosures

Catherine Chappell, MD, MSc, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Organon: Grant/Research Support
1940. Real-Life Impact of Pneumococcal Conjugate Vaccines (PCVs) on Hospitalization of Young Children with RSV-Associated Community-acquired Alveolar Pneumonia (CAAP)
Authors: Dagan Ron , van der Beek Bart Adriaan , Greenberg David , Ben-Shimol Shalom
Published: November 2023

Background

The important role of streptococcus pneumoniae in pediatric community-acquired alveolar pneumonia (CAAP) has been demonstrated, mainly through PCV impact on CAAP rates in young children, in whom RSV is also frequently detected. The causative role of RSV on CAAP has been strongly suggested from multiple epidemiological studies. Although pneumococcal-RSV coinfections in pneumonia were suggested by a pre-licensee PCV9 study, no solid real-life data were generated to substantiate the potential effect of PCVs on RSV-associated CAAP (RSV-CAAP). The current prospective study evaluates the impact of PCV7/PCV13 implementation in Israel on all-cause CAAP and RSV-CAAP incidence dynamics in young children during RSV seasons.

Methods

PCV7/PCV13 were implemented in Israel in July 2009/November 2010. A prospective population-based surveillance on CAAP rates in children < 5 years in southern Israel has been ongoing since 2002 (Ben-Shimol, CID 71:177, 2020). Nasal samples of RSV (by PCR) were tested in most episodes and were extrapolated for total CAAP episodes. RSV season was defined as all months with >5 positive RSV tests in southern Israel. The impact was determined by incidence rate ratio (IRR) comparing each RSV season (and the four years 2015-19 combined) to the five pre-PCV implementation years, 2004-09, combined).

Results

From Jul-2004 to Jun-2019, 7,654 CAAP episodes were recorded; 3,661 (47.8%) were tested for RSV, of which 1,662 (45.4%) were positive. The seasonal proportions of RSV-CAAP of all episodes ranged from 37.4% to 67.2%. Compared to 2004-09 (combined), IRR (95% CI) for 2015-19 were 0.68 (0.56-0.84) for RSV CAAP and 0.70 (0.61 – 0.80) for all-cause CAAP (Table, Figure). Generally, yearly seasonal IRRs for all-cause CAAP and RSV-CAAP were similar.

Conclusion

The abrupt, steep , and seasonal reduction of hospitalization of young children for both all-cause CAAP and RSV-CAAP strongly support the important role of RSV-S. pneumoniae coinfections in CAAP. The dynamics observed in CAAP and other pneumococcus-associated diseases in association with RSV activities during COVID-19 (Dagan, EBioMedicne, 90:104993, 2023) together with the real-life impact of PCVs on RSV-CAAP confirm the mutual role of RSV and S. pneumoniae in CAAP.

Disclosures

Ron Dagan, Professor MD, GSK: Honoraria|MedIMmune/AstraZeneca: Grant/Research Support|MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Expert Testimony|Pfizer: Grant/Research Support|Pfizer: Honoraria|Sanofi Pasteur: Honoraria David Greenberg, Professor MD, GSK: Advisor/Consultant|GSK: Honoraria|MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Honoraria Shalom Ben-Shimol, Dr. MD, GSK: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria
1945. Antibacterial activity of cefepime/enmetazobactam and comparator agents against U.S. Enterobacterales clinical isolates collected from 2019-2021
Authors: Belley Adam , Kothari Nimmi , Monti Federica , Hawser Stephen
Published: November 2023

Background

The investigational β-lactam/β-lactamase inhibitor combination of cefepime/enmetazobactam (FPE) met criteria for non-inferiority and superiority compared to piperacillin-tazobactam (PTZ) in a phase 3 clinical trial of adult patients with complicated urinary tract infections/acute pyelonephritis. FPE has demonstrated potent in vitro antibacterial activity against Gram-negative pathogens expressing extended spectrum β-lactamases (ESBL), the leading cause of resistance to 3rd-generation cephalosporins (3GC). In this study, the in vitro activity of FPE and comparator agents was assessed against Gram-negative clinical isolates obtained from the U.S. between 2019 and 2021.

Methods

Broth microdilution minimum inhibitory concentrations (MIC) were determined for 2,241 Enterobacterales clinical isolates following CLSI guidelines. For determination of phenotypic resistance to 3GC, isolates resistant to both ceftriaxone and ceftazidime but susceptible to the carbapenem meropenem (MEM) were selected. ESBL genotyping was performed using a multiplex PCR method. Cefepime breakpoints of susceptible (S) ≤2 µg/ml and susceptible-dose dependent (SDD) ≤8 µg/ml were used as provisional breakpoints for FPE.

Results

FPE demonstrated potent in vitro activity against the surveillance isolates obtained from US medical centers, with an MIC90 of 0.12 µg/ml that was comparable to those of MEM (0.06 µg/ml) and ceftazidime/avibactam (CZA; 0.25 µg/ml). When applying cefepime breakpoints, susceptibility to FPE was ≥98.4 µg/ml whereas susceptibility to 3GCs and PTZ was ≤85.8%. Against Enterobacterales with either an ESBL genotype or exhibiting a 3GC-resistant phenotype, FPE retained potent in vitro activity (MIC90 = 0.5 and 1 µg/ml) and provisional susceptibility was ≥95.6%. In contrast, susceptibility to 3GCs and PTZ ranged from 0.0 to 65.9%.

Summary of the in vitro activity of cefepime/enmetazobactam and comparator agents against US Enterobacterales clinical isolates collected from 2019-2021

Conclusion

These results demonstrate that diminished susceptibility to 3GCs and piperacillin/tazobactam has compromised their reliability as empiric therapies. Cefepime/enmetazobactam demonstrates potent in vitro activity comparable to meropenem against ESBL-producing Enterobacterales and is intended as empiric therapy in settings where ESBL are endemic.

Disclosures

Adam Belley, PhD, Allecra Therapeutics SAS: Advisor/Consultant Nimmi Kothari, PhD, Allecra: Allecra (study funding)|Innoviva Specialty Therapeutics, Inc.: Honoraria|Roche: Honoraria|Roche: This project has been funded by BARDA (HHSO100201600038C). Federica Monti, PhD, Allecra: Study funded|Innoviva Specialty Therapeutics, Inc.: Honoraria Stephen Hawser, PhD, Allecra: study funding|Innoviva Specialty Therapeutics, Inc.: Honoraria|Roche: Honoraria|Roche: This project has been funded by BARDA (HHSO100201600038C).
1163. Influenza Vaccination Coverage through December among Persons Ages Six Months and Older in the Vaccine Safety Datalink, 2017-18 through 2022-23 Influenza Seasons
Authors: Irving Stephanie , Groom Holly C , Belongia Edward , Crane Bradley , Daley Matthew F , Goddard Kristin , Jackson Lisa , Kenigsberg Tat’Yana A , Kuckler Leslie , Naleway Allison L , Patel Suchita A , Tseng Hung Fu , Williams Joshua T B , Weintraub Eric
Published: November 2023

Background

In the United States, annual vaccination against seasonal influenza is recommended for all people ages ≥ 6 months. Vaccination coverage assessments can identify populations with lower vaccination rates and help to tailor vaccination efforts. Within the Vaccine Safety Datalink population ages ≥ 6 months, we report influenza vaccination coverage through December of the 2022-23 influenza season and compare estimates to similar periods within the 2017-18 through 2021-22 seasons.

Methods

Using electronic health record data, we captured all influenza vaccines administered between August 1 and December 31 of each season. Crude, single-dose coverage was calculated for each season, overall and by sex; age group; race and ethnicity; and number of separate categories of diagnoses associated with an increased risk of severe illness and complications from influenza – these conditions were identified using ICD-10-CM diagnosis codes assigned in the year preceding each influenza season.

Results

Among cohorts of more than 11 million individuals each season, crude influenza vaccination coverage through December ranged from a high of 44% (2020-21) to a low of 37% (2022-23). In each of the six seasons, coverage was lowest among males, 18-49-year-olds (Figure), non-Hispanic Black people, and those without conditions associated with increased risk of severe illness and complications from influenza. While decreases in coverage in recent seasons were present in all age groups, the declines were most dramatic among children: during the 2022-23 season, coverage for children ages < 9 and 9-17 years decreased 25% and 26% (12 and 10 absolute percentage points), respectively, from peak coverage in prior seasons (Figure).

Conclusion

Influenza vaccination coverage increased from the 2017-18 through 2020-21 seasons, then decreased to the lowest level in the 2022-23 season. Overall Vaccine Safety Datalink population estimates are far below United States vaccination targets. We identified persistent disparities in influenza vaccination coverage by sex, age, and race and ethnicity. The overall low coverage, disparities in coverage, and recent decreases in coverage raise significant public health concerns.

Disclosures

Edward Belongia, MD, Seqirus: Grant/Research Support Lisa Jackson, MD, MPH, Pfizer: Grant/Research Support Hung Fu Tseng, PhD MPH, GSK: Grant/Research Support|Moderna: Grant/Research Support