bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of coronary revascularisation guided by cardiovascular magnetic resonance to predict death
Authors: Unger A , Lequipar A , Garot P , Toupin S , Sanguineti F , Hovasse T , Duhamel S , Akodad M , Goncalves T , Dillinger J G , Henry P , Bondue A , Bousson V , Pezel T , Garot J
Published: January 2025

Background

After the REVIVED trial, the utility of cardiovascular magnetic resonance (CMR) assessing the myocardial viability to guide coronary revascularisation remains controversial.

Objective

To assess the prognostic impact of coronary revascularisation guided by CMR-based myocardial viability to predict death in patients with ischaemic cardiomyopathy (ICM) and reduced left ventricular ejection fraction (LVEF) <50%.

Methods

From 2008 to 2022, we included all consecutive ICM patients referred for CMR-based myocardial viability assessment in a multicentric study. Eligible patients had ≥70% stenosis in ≥1 epicardial coronary vessel on angiography, a history of myocardial infarction, or prior coronary revascularisation, and LVEF<50%. We collected data on revascularisation within 90 days of the index CMR. The primary endpoint was all-cause mortality. To define myocardial viability, ischaemic-late gadolinium enhancement (LGE) transmurality was assessed for maximal scar depth, considering myocardium with LGE transmurality <50% as viable and ≥50% as non-viable.

Results

Among 6,082 patients (mean age 65±12 years; 73% male), 3,591 (59%) exhibited ischaemic-LGE. Revascularisation was performed in 2,773 (46%) patients within 90 days of CMR. Revascularisation was more frequent in patients with viable myocardium (88%) than in those with non-viable myocardium (67%, Figure 1). Over a median follow-up of 9 years (interquartile range 7-12 years), 652 patients (11%) died. Using a Cox regression analysis, revascularisation was associated with a reduced risk of mortality (HR: 0.73 95% CI: 0.58-0.91, p<0.001, Figure 2A). Patients with LGE and myocardial viability who underwent revascularization had a similar prognosis to those without LGE (p=0.48). Interestingly, patients who underwent revascularisation with myocardial viability had better outcomes than those who underwent revascularisation without myocardial viability (p<0.001, Figure 2B).

Conclusion

In a large cohort of ICM patients, coronary revascularisation was beneficial and was associated with improved survival outcomes. The impact of this revascularisation was stronger in patients with myocardial viability assessed by CMR than patients without myocardial viability.

Revascularisation in the ICM population

Survival curves
Lung ultrasound performance in predicting cardiovascular outcomes for patients with STEMI: a systematic review and meta-analysis
Authors: Aziri B , Begic E , Vilbert M , Gewehr D , Bulhoes E , Guida C
Published: January 2025

Background

Lung ultrasound (LUS) is a valuable, non-invasive tool for detecting pulmonary congestion in patients with acute heart failure (AHF), with a higher sensitivity relative to physical examination. However, the association between LUS-detected pulmonary congestion and cardiovascular outcomes in patients with ST-segment elevation (STEMI) is not well established.

Purpose

This systematic review and meta-analysis evaluated cardiovascular outcomes in patients with STEMI and congested (wet) or non-congested (dry) lungs by LUS.

Methods

We searched PubMed, Embase, and Cochrane databases, and conference abstracts for clinical trials evaluating LUS-congestion (LUS+) versus non-LUS-congestion (LUS-) in patients with STEMI. Risk ratios (RRs) and hazard ratios (HR) with 95%CIs were pooled using R software under random-effects models. We also calculated LUS sensitivity, specificity, and area under the curves (AUCs) for the prediction of in-hospital mortality and cardiogenic shock.

Results

We included five studies with 1,454 patients. The mean age was 60 to 65 years; 1,066 (73.3%) were male, and 451 (31%) had congested lungs (LUS+). Patients with congestion on LUS had a significantly higher risk of the composite endpoint of death, heart failure, acute coronary syndrome, and cardiogenic shock (HR 4.00; 95%CI 2.12-7.54; p<0.01; Figure 1A). There was also a higher risk of in-hospital mortality (RR 5.09; 95%CI 2.25-11.49; p<0.001; Figure 1B) and cardiogenic shock (RR 5.01; 95%CI 2.47-10.17; p<0.001; Figure 1C) compared to patients with non-congested lungs. Reinfarction was similar between groups (p=0.08; Figure 1D). LUS had high diagnostic accuracy for in-hospital mortality (SROC-AUC: 0.82) and cardiogenic shock (SROC-AUC: 0.77); a high sensitivity (0.84; 95%CI 0.49-0.97; Figure 2A), and moderate specificity (0.78; 95%CI 0.67-0.87; Figure 2A) for in-hospital mortality; and moderate sensitivity (0.75; 95%CI 0.42-0.93; Figure 2B) and specificity (0.76; 95% CI 0.61-0.87; Figure 2B) for cardiogenic shock.

Conclusions

Congested lungs on LUS are significantly associated with a higher risk of in-hospital mortality and cardiogenic shock in patients with STEMI. Moreover, LUS has a high AUC for identifying in-hospital mortality and cardiogenic shock in this patient population.

Figure 1

Figure 2
Unveiling the prognostic power of a new marker: right ventricular scalloping index in ARVC patients-a multimodality imaging study
Authors: Ayduk Govdeli E , Yavuz M L , Dursun M , Bilge A K , Karaca Ozer P
Published: January 2025

Objectives

ARVC, a rare form of cardiomyopathy associated with a dismal prognosis, involves the replacement of cardiac myocytes with fibrofatty tissue1,2. Multiple criteria are utilized for diagnosis and risk assessment3–5. The right ventricular scalloping index has emerged as a newly proposed parameter for ARVC diagnosis, yet its prognostic implications remain unexplored in the literature6. Our study seeks to investigate the prognostic impact of cardiac MRI derived index (RVSI-MR) alongside other parameters.

Material and Methods

The study retrospectively enrolled 27 patients diagnosed with ARVC at our clinic. Primary outcomes encompassed all-cause mortality, sudden cardiac death, sustained ventricular arrhythmia, and ablation necessitated by ventricular arrhythmia. Comparative analysis, particularly focusing on the right ventricular scalloping index, was conducted on clinical, imaging, and electrocardiographic parameters within primary outcome groups. Additionally, Cox regression analysis was employed to identify parameters influencing prognosis.

Results

The average age was 42.59 ± 16.8 years, with males constituting 81.5% of the patient cohort. The median follow-up period was 134 months (0-236). Notably, in patients with the primary outcome, RVSI-MR was significantly higher (1.32 ± 0.1 vs 1.46 ± 0.2, p-value 0.007), while RVEF-MR was notably lower (54.91 ± 10.1 vs 41.32 ± 12.9, p-value 0.007). Furthermore, RVSI-MR exhibited a positive correlation with the RV mid diameter-TTE and a negative correlation with RVEF-MR (r=0.428, p-value 0.029, r=-0.477, p-value 0.016, respectively). Cox regression analysis identified RV dysfunction at diagnosis and RVEF-MR as predictors of prognosis (HR 29.364, p-value 0.004, HR 0.863, p-value 0.021, respectively). Additionally, ROC analysis revealed that an RVSI-MR value exceeding 1.43 predicted the primary outcome with 72.73% sensitivity and 87.50% specificity (AUC 0.609, p-value 0.002), while an RVEF-MR value of ≤ 49.71% predicted the primary outcome with 70% sensitivity and 73.33% specificity (AUC 0.787, p-value 0.004).

Conclusion

The right ventricular scalloping index represents a novel and easily applicable cardiac MRI parameter useful for ARVC diagnosis and risk stratification.
Imaging features of non-dilated left ventricular cardiomyopathy: differences and similarities with dilated cardiomyopathy
Authors: Olmos C , Zulet P , Sanchez I , Goirigolzarri J , Restrepo A , Poveda V , Davila C , De Agustin J A , Islas F
Published: January 2025

Background and Aim

The spectrum of dilated cardiomyopathy (DCM) includes both patients with ventricular dilation and those with systolic dysfunction and no dilation. This latter entity has been called hypokinetic non-dilated cardiomyopathy (H-NDLVC).

Our aim was to describe the epidemiological, clinical and imaging features of patients with DCM, comparing those cases of H-NDLVC with patients with classic dilated cardiomyopathy.

Methods

From January 2014 to December 2022, all patients with a new diagnosis of DCM studied at our tertiary hospital were prospectively included in a multipurpose registry. Transthoracic echocardiogram and cardiac magnetic resonance (CMR) imaging were performed as part of the study. During follow-up, hospitalizations for heart failure (HF), arrhythmic events and mortality were recorded.

Results

The median age of the patients (n = 227) was 63.8 (53-74) years, and 31.7% were women. Median follow-up was 34.3 (20-56) months. 176 patients (77.5%) had DCM, and 51 patients (22.5%) had H-NDLVC.

Epidemiological, clinical, and cardiac imaging characteristics of both groups are shown in the Table. The proportion of men was higher in patients with H-NDLVC, and the presence of left bundle branch block was also more frequent in this group (Figure 1).

No differences were found in the distribution of cardiovascular risk factors or comorbidities.

Patients with DCM had greater left atrial dilation and more significant mitral regurgitation, as well as worse diastolic function.

In relation to the CMR findings, the presence of late enhancement and late enhancement with a high-risk pattern was similar between both groups (Figure 2).

Both groups experienced significant improvement in LV systolic volumes (77ml/m2 vs 45 mL/m2 in DCM and 38 ml/m2 vs 28 mL/m2 in H-NDLVC; p<001) and LV ejection fraction (29% vs 43% in DCM and 36% vs 51% in H-NDLVC; p<001) during follow-up.

Interestingly, in the subset of patients who had genetic information available (n=78), we found a trend towards higher frequency of positive genetic testing in the group of patients with H-NDLVC (31.2 vs 17.7%; p=0.107).

There was a non-significant trend towards lower incidence of events (hospitalization for HF, ventricular arrhythmias, mortality) in patients with H-NDLVC.

Conclusions

H-NDLVC represent one in 5 patients in our DCM cohort. These patients have less reduction in systolic function, less alteration in diastolic function and less frequency of significant mitral regurgitation. However, the percentage of patients with late gadolinium enhancement and a high-risk pattern is similar to those with true ventricular dilation, and genetic testing was positive in one out of three patients tested. Thus, these patients benefit from an integrated approach with using advance imaging and genetics.

Clinical characteristics

Imaging findings
Negative Aging Stereotypes and Clinical Insomnia in Older U.S. Military Veterans
Authors: Boyle Julia T , Fischer Ian , Bashian Hannah M , Moye Jennifer , Levy Becca R , Pietrzak Robert H
Published: January 2025

Background and Objectives

Insomnia symptoms are more prevalent in older age and may be impacted by negative perceptions of aging; however, more research is needed. The present study characterizes the relationship between negative aging stereotypes and clinical insomnia symptoms in a nationally representative sample of older United States (U.S.) veterans.

Research Design and Methods

Data were analyzed from 3,000 U.S. veterans (aged 60-99) who participated in the National Health and Resilience in Veterans Study (NHRVS). Multivariable regression analyses were conducted to examine associations between negative aging stereotypes (assessed with the Expectations Regarding Aging Scale) and clinical insomnia (assessed with the Insomnia Severity Index).

Results

A total of 213 veterans (7.1%) screened positive for clinical insomnia and scored significantly higher on measures of negative emotional (p<.001), physical (p=.003), and cognitive (p=.013) aging stereotypes relative to veterans without clinical insomnia. Multivariable regression analyses revealed that, after adjusting for covariates, greater endorsement of negative stereotypes regarding emotional aging was associated with significantly greater odds of screening positive for clinical insomnia (OR=1.56, 95%CI=1.26-1.95, p<.001), sleep disturbance (OR=1.49, 95%CI=1.25-1.77, p<.001) and daytime dysfunction (OR=1.58, 95%CI=1.34-1.88, p<.001). Veterans who ‘somewhat’ and ‘fully’ endorsed these negative stereotypes were 3- and 6-times more likely to screen positive for clinical insomnia, respectively (probabilities=0.110 and 0.246 vs. 0.040).

Discussion and Implications

Negative aging stereotypes, particularly those related to emotional aging, are independently associated with clinical insomnia in older U.S. veterans. Efforts to modify these stereotypes in older veterans may help improve overall sleep quality.
Structure and release function of fragrance glands
Authors: Chen Yunyi , Jiang Ziying , Wu Sihui , Cheng Bixuan , Zhou Lijun , Liu Tinghan , Yu Chao
Published: January 2025

Volatile compounds serve physiological, signaling, and defensive purposes in plants and have beneficial effects on the growth, reproduction, resistance, and yield of horticultural plants. They are released through fragrance glands and become gasses by passing through the plasma membrane, cell walls that contain water, and cuticle. Transporter proteins facilitate their transport and reduce the resistance of these barriers. They also regulate the rate of release and concentration of volatiles inside and outside of the membrane. However, there has been no summary of the structure and function of the fragrance glands of horticultural plants, as well as an introduction to the latest research progress on the mechanism of the transport of volatiles. This review focuses on the structure and function of the release of aromas in horticultural plants and explores the mechanism of the release of volatiles through a transporter model. Additionally, it considers the factors that affect their release and ecological functions and suggests directions for future research.
Do patients with ischaemic cardiomyopathy benefit from off-pump coronary bypass surgery? (from the krok registry)
Authors: Kosiorowska Kinga , Jasiński Marek , Przybylski Roman , Deja Marek , Rogowski Jan , Gerber Witold , Pacholewicz Jerzy , Cichoń Romuald , Cisowski Marek , Pawliszak Wojciech , Bugajski Paweł , Krejca Michał , Hirnle Tomasz , Perek Bartłomiej , Tobota Zdzisław , Maruszewski Bohdan , Hrapkowicz Tomasz ,   On Behalf Of KROK Investigators
Published: January 2025

OBJECTIVES

This study aimed to compare perioperative outcomes and long-term mortality between off-pump coronary artery bypass grafting and on-pump coronary artery bypass grafting in patients with ischaemic cardiomyopathy who had a left ventricle ejection fraction of ≤ 35%.

METHODS

A retrospective cohort analysis was conducted using data from the Polish National Registry of Cardiac Surgery Procedures (KROK) database, encompassing patients who underwent isolated coronary artery bypass grafting in Poland between 2012 and 2022. Patients were divided into two groups: on-pump and off-pump. Propensity score matching was used to balance the groups. The primary outcome was long-term all-cause mortality following surgical revascularization.

RESULTS

A total of 9,920 patients were included, with 3,116 patients in each group after propensity score matching. The median follow-up period was 4 years. The off-pump group was associated with a lower 30-day mortality rate (6.4% vs 9.1%, p = 0.002) and fewer perioperative complications. However, long-term survival analysis revealed a modest but statistically significant advantage for on-pump group at the 10-year follow-up (p = 0.047).

CONCLUSIONS

Off-pump provides short-term benefits, including reduced early mortality and fewer complications compared to on-pump technique. However, these advantages do not translate into improved long-term survival, where on-pump demonstrates a slight benefit. The choice between off-pump and on-pump technique should be individualized based on patient-specific factors and surgical expertise.
Operator Systems Generated by Projections
Authors: Araiza Roy , Russell Travis
Published: January 2025

We construct a family of operator systems and $k$-AOU spaces generated by a finite number of projections satisfying a set of linear relations. This family is universal in the sense that the map sending the generating projections to any other set of projections which satisfy the same relations is completely positive. These operator systems are constructed as inductive limits of explicitly defined operator systems. By choosing the linear relations to be the nonsignalling relations from quantum correlation theory, we obtain a hierarchy of ordered vector spaces dual to the hierarchy of quantum correlation sets. By considering another set of relations, we also find a new necessary condition for the existence of SIC-POVM’s.
Controlled Human Infection Studies Accelerate Vaccine Development
Authors: Laurens Matthew B
Published: January 2025

Clinical trials that use human challenge, also known as controlled human infection models (CHIMs), have rapidly advanced vaccine development for multiple pathogens, including at least 30 disease models to date. CHIM studies, championed by networks of researchers, regulators, ethicists, technical experts, and other stakeholders, limit exposure of individuals to an investigational product, de-risk product investments, identify correlates of protection, and, most importantly, provide a prompt readout of vaccine efficacy. While CHIM studies provide multiple advantages, important challenges exist, including strengthening the relevance and comparability of CHIM study results to efficacy trials in endemic areas, particularly in resource-limited settings.
Breed and trace mineral source influence the performance of beef heifers during periods of nutrient restriction and grazing forage at early vegetative stage
Authors: Souza Isabella R T , Moriel Philipe , dos Santos Taynara C , de Miranda André V , Monar Gabriel R R , Rezende Maria E , Augusto Karolina V Z , Porcionato Marco A F , Sanz-Fernandez M Victoria , Souza Izadora S , Mackey Shea J , Cooke Reinaldo F , Vendramini J M B , Araujo Davi B , Vasconcelos José L M
Published: January 2025

We evaluated the effects of breed and mineral source on heifer performance during periods of nutrient restriction and grazing. On day -7, ½ Angus × ½ Nelore (ANE) and Nelore (NE) heifers (12 heifers per breed; body weight, BW = 264 ± 35 kg; age = 15 ± 1 mo) were assigned to individual drylot pens to receive ad libitum Tifton 85 (Cynodon sp.) hay and white salt for 7 days. On day 0, within each breed, heifers were randomly assigned (2 × 2 factorial arrangement) to receive protein supplementation (0.20% of BW; dry matter, DM) added with sulfate (SUL) or hydroxychloride (HYD) sources of Cu, Mn, and Zn from day 0 to 49. From day 0 to 34, hay DM intake was restricted to 50% of the ad libitum intake recorded from day -7 to -1. On day 35, heifers were transferred to individual pastures to graze Tifton 85 forage at early vegetative stage until day 49. No effects of breed × mineral source × day and breed × mineral source were detected (P ≥ 0.11). Nelore heifers had greater (P ≤ 0.02) average daily gain (ADG) from day 0 to 35 and day 0 to 49 compared to ANE heifers. Cumulative diarrhea incidence, fecal pH and total days of diarrhea symptoms did not differ (P ≥ 0.19) between breeds. Nelore heifers had greater (P ≤ 0.05) serum concentrations of insulin-like growth factor 1 (IGF-1) from day 35 to 45 but had less (P ≤ 0.05) serum concentrations of cortisol and haptoglobin on day 42 and 45, respectively. Serum concentrations of urea N were greater (P ≤ 0.05) for NE vs. ANE heifers on days 0 and 42 and were less (P ≤ 0.05) for NE vs. ANE on days 38, 45 and 49. Heifers supplemented with HYD had (P ≤ 0.05) greater ADG from day 0 to 35, lower cumulative diarrhea incidence and percentage of heifers exhibiting ≥ 2 days of diarrhea from day 36 to 49, less serum concentrations of non-esterified fatty acids (NEFA) on day 35, and less serum concentrations of NEFA, cortisol and urea N on day 38 compared to SUL heifers. In summary, breed influenced serum concentrations of haptoglobin, cortisol, urea N, insulin and IGF-1, and the growth of beef heifers during nutrient restriction, but did not impact growth and incidence of diarrhea during periods of grazing forage at early vegetative stage. Regardless of breed, replacing sulfate with hydroxychloride sources of Cu, Mn, and Zn led to minimal reductions on serum concentrations of NEFA, cortisol and urea N, enhanced growth during nutrient restriction, and reduced diarrhea incidence during grazing of early vegetative forage.
Overseas-acquired infections in travellers returning to Queensland, Australia
Authors: Furuya-Kanamori Luis , Young Megan , Williams Olivia , Vasant Bhakti , Mills Deborah J , Lau Colleen L , Smoll Nicolas
Published: January 2025

A total of 7448 cases of overseas-acquired infections reported between 2009 and 2023 in Queensland were analysed. Vector-borne diseases (56.7%) were most common, with dengue and malaria leading. Vaccine-preventable diseases (32.8%) highlighted low vaccination uptake (16.8%). Findings stress the need for enhanced pre-travel health awareness, improved vaccination coverage and targeted vector-borne diseases prevention strategies.
Comparative population genomics unveils congruent secondary suture zone in Southwest Pacific Hydrothermal Vents
Authors: Tran Lu Y Adrien , Ruault Stéphanie , Daguin-Thiébaut Claire , Le Port Anne-Sophie , Ballenghien Marion , Castel Jade , Gagnaire Pierre-Alexandre , Bierne Nicolas , Arnaud-Haond Sophie , Poitrimol Camille , Thiébaut Eric , Lallier François H , Broquet Thomas , Jollivet Didier , Bonhomme François , Hourdez Stéphane
Published: January 2025

How the interplay of biotic and abiotic factors shapes current genetic diversity at the community level remains an open question, particularly in the deep sea. Comparative phylogeography of multiple species can reveal the influence of past climatic events, geographic barriers, and species life history traits on spatial patterns of genetic structure across lineages.

To shed light on the factors that shape community-level genetic variation and to improve our understanding of deep-sea biogeographic patterns, we conducted a comparative population genomics study on seven hydrothermal vent species co-distributed in the Back-Arc Basins (BABs) of the Southwest Pacific region. Using ddRAD-seq, we compared the range-wide distribution of genomic diversity across species and discovered a shared phylogeographic break. Demogenetic inference revealed shared histories of lineage divergence and a secondary contact. Low levels of asymmetric gene flow probably occurred in most species between the Woodlark and North Fiji basins, but the exact location of contact zones varied from species to species. For two species, we found individuals from the two lineages co-occurring in sympatry in Woodlark Basin. Although species exhibit congruent patterns of spatial structure (Eastern vs Western sites), they also show variation in the degree of divergence among lineages across the suture zone. Our results also show heterogeneous gene flow across the genome, indicating possible partial reproductive isolation between lineages and early speciation.

Our comparative study highlights the pivotal role of historical and contemporary factors, underscoring the need for a comprehensive approach—especially in addressing knowledge gaps on the life history traits of deep-sea species.
Selection of initiator tRNA and start codon by mammalian mitochondrial initiation factor 3 in leaderless mRNA translation
Authors: Lee Muhoon , Wakigawa Taisei , Jia Qimin , Liu Chang , Huang Ruiyuan , Huang Shuai , Nagao Asuteka , Suzuki Tsutomu , Tomita Kozo , Iwasaki Shintaro , Takeuchi-Tomita Nono
Published: January 2025

The mammalian mitochondrial protein synthesis system produces 13 essential subunits of oxidative phosphorylation (OXPHOS) complexes. Translation initiation in mammalian mitochondria is characterized by the use of leaderless messenger RNAs (mRNAs) and non-AUG start codons, where the proofreading function of IF-3mt still remains elusive. Here, we developed a reconstituted mammalian mitochondrial translation system using in vitro transcribed and native mitochondrial transfer RNAs (tRNAs) to investigate IF-3mt’s proofreading function. Similar to bacterial IF-3, IF-3mt permits an initiator tRNA to participate in initiation by discriminating the three G–C pairs in its anticodon stem, and by the cognate interactions of its anticodon with the AUG start codon. As a result, IF-3mt promotes the accurate initiation of leaderless mRNAs. Nevertheless, IF-3mt can also facilitate initiation from the non-AUG(AUA) start codon through its unique N- and C-terminal extensions, in concert with the 5-methylcytidine (m5C) or 5-formylcytidine (f5C) modification at the anticodon wobble position of mt-tRNAMet. This is partly because the IF-3mt-specific N- and C-terminal extensions and the KKGK-motif favor leaderless mRNA initiation and relax non-AUG start codon discrimination. Analyses of IF-3mt-depleted human cells revealed that IF-3mt indeed participates in translating the open reading frames (ORFs) of leaderless mRNAs, as well as the internal ORFs of dicistronic mRNAs.
The ortholog of human DNAJC9 promotes histone H3–H4 degradation and is counteracted by Asf1 in fission yeast
Authors: Ding Yan , Li Jun , Jiang He-Li , Suo Fang , Shao Guang-Can , Zhang Xiao-Ran , Dong Meng-Qiu , Liu Chao-Pei , Xu Rui-Ming , Du Li-Lin
Published: January 2025

Mammalian J-domain protein DNAJC9 interacts with histones H3–H4 and is important for cell proliferation. However, its exact function remains unclear. Here, we show that, in the fission yeast Schizosaccharomyces pombe, loss of Djc9, the ortholog of DNAJC9, renders the histone chaperone Asf1 no longer essential for growth. Utilizing AlphaFold-based structural prediction, we identified a histone-binding surface on Djc9 that binds to helix α3 of H3 in a manner that precludes simultaneous helix α3-binding by Asf1. Djc9 and Asf1 indeed compete for binding to the H3–H4 dimer in vitro, and an H3-α3 mutation impeding Djc9 binding also renders Asf1 non-essential, indicating that the role of Asf1 needed for growth in fission yeast is to prevent histone binding by Djc9. In the absence of Asf1, cell growth is hindered due to unrestrained Djc9-mediated downregulation of H3 and H4. In the presence of Asf1, Djc9 confers resistance to the DNA replication inhibitor hydroxyurea and dominant negative disease-related histone mutants by promoting the degradation of superfluous or dysfunctional histones. Our findings provide new insights into the function and mechanism of this conserved histone-binding protein.
The Promotion of Oral Nicotine Pouches for Non-Smoking Cessation Purposes on TikTok
Authors: Zenone Marco , Harries Bethan , Hartwell Greg
Published: January 2025

Introduction

Oral nicotine pouches (ONPs) are increasingly prevalent among young people and feature widely within social media content. This study systematically analyzes the most viewed videos on TikTok relating to ZYN (the most popular ONP, manufactured by a subsidiary of Philip Morris International) to understand their content sentiment and patterns, as well as the demographics and potential commercial biases of their creators.

Methods

We used an Apify scraper in July 2024 to collect URLs and metadata for the top 100 most viewed videos on TikTok under the #ZYN hashtag. Profiles of content creators, plus their externally linked sites, were examined for commercial connections to ONP entities. We then undertook an inductive manifest content analysis.

Results

The top 100 TikTok videos identified garnered over 400 million views and over 3.8 million shares. 10.3% (n=9) of content creators had an external link to a website which sold ONPs. Videos predominantly indicated positive sentiment towards ZYN products or other ONPs (79%), and portrayed young men enthusing about the products, often employing humour. ZYN products featured directly in 71% of videos. Few videos contained disclaimers or warnings about potential risks of ONPs and only 5% portrayed ZYN as a vaping or smoking cessation tool.

Discussion

Our findings suggest the most widely viewed content relating to ZYN on TikTok is overwhelmingly positive in sentiment, commonly featuring young men and often portraying ONP use in a humorous context, minimising risks. Many content creators actively sell ONP products through TikTok, some overtly and some via external links.

IMPLICATIONS

ZYN oral nicotine pouches are presented positively and primarily for recreational purposes on TikTok. Few videos referenced ZYN for smoking cessation purposes or mentioned the risks of nicotine. Nearly 10% of the creators linked their profile to an external website selling oral nicotine pouches, which appears inconsistent with TikTok’s policies. The use of humour and downplaying or omission of addiction and health risks across most of the sample echoes marketing efforts by the tobacco industry to present oral nicotine pouches as fun and safe.
380. Implementation of Pooled Saliva Tests for Universal Screening of Congenital Cytomegalovirus (cCMV) Infection: Lessons Derived Over a 25-Months Period
Authors: Oiknine-Djian Esther , Eventov Friedman Smadar , Ofek Shlomai Noa , Yassour Moran , Wolf Dana
Published: January 2025

Background

cCMV infection is the most common intrauterine infection, leading to infant neurodevelopmental disabilities and hearing loss, which can manifest at birth or develop later during childhood. Currently, targeted screening of cCMV by PCR testing of saliva samples is employed in many centers. However, targeted screening of high-risk neonates misses the majority of infants with cCMV who are asymptomatic at birth, yet are at risk for late-onset sequelae. Thus, universal newborn screening of cCMV has been increasingly advocated. In the absence of a high-throughput screening test that can identify all infected neonates, the development of an accurate and efficient testing strategy for universal cCMV screening has remained an ongoing challenge. We have recently reported on the development of a new saliva pooling setup for universal screening of cCMV (Nature Medicine 2024). Here we report on lessons derived over a 25-months period of its routine implementation.

Methods

This prospective study took place in 2 hospitals of Jerusalem from April 2022 through April 2024. Saliva samples of all newborns with parental consent were tested for cCMV in 8-sample pools. Positive saliva results were confirmed by urine testing.

Results

During the study period, 32,413 infants (94.4% of all live newborns) were screened for cCMV using the pooled approach. The pooling strategy proved highly efficient, with each PCR test covering an average of 6 newborns during the first 13 months of the study, thus reducing the number of required saliva tests by 83%. PCR loss of sensitivity was minor, in accordance with the theoretical prediction for an 8-sample pool. cCMV was identified in 123 newborns, with a birth prevalence of 3.8 per 1000. Over half (57.7%) of infants with cCMV identified by universal screening were asymptomatic at birth and would have been missed by targeted screening.

Conclusion

The study demonstrates the wide feasibility and benefits of pooled-saliva cCMV testing as an accurate and cost-sparing approach, which could revolutionise the implementation of universal cCMV screening. Beyond the clinical implications toward early diagnosis, monitoring and treatment of cCMV, data derived from the implemented universal screening will serve to define the burden, risk factors, and long-term clinical outcomes of cCMV.

Disclosures

Dana Wolf, MD, GSK: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Grant/Research Support|MSD: Advisor/Consultant|Takeda: Advisor/Consultant
90. Impact of anti-CD20 therapy on COVID-19 in immunocompromised patients: A nationwide cohort study in Korea
Authors: Mi Lee Chan , Kim Suhyun , Kim Seungyeon , Bae Jiyeon , Jae Jo Hyeon , Kyung Kang Chang , Gyun Choe Pyoeng , Beom Park Wan , Joong Kim Nam
Published: January 2025

Background

During the coronavirus disease 2019 (COVID-19) pandemic, we observed that patients received anti-CD20 therapy progressed to severe pneumonia and underwent persistent viral shedding. We aimed to identify the association between anti-CD20 therapy and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as well as the outcomes of COVID-19.

Methods

Using claims data derived from the Korean National Health Insurance Service, we conducted a matched nationwide retrospective cohort study. We included individuals aged ≥ 20 years diagnosed with conditions for which anti-CD20 therapy could be considered from January 2020 to December 2021. We defined the exposure variable by prescribing rituximab (RTX) at least once according to the database. COVID-19-related outcomes included hospitalization for COVID-19, ICU admission, mechanical ventilation administration, and all-case death. Patients prescribed RTX and those not prescribed RTX were defined as RTX users and non-users, respectively. The RTX users and non-users were 1:10 propensity score matched using sex, age, insurance type, and comorbidities. Logistic regression analyses were used to estimate the association between RTX and SARS-CoV-2 infection, as well as COVID-19-related outcomes.

Results

After 1:10 propensity score matching, 932 RTX users and 8,361 RTX non-users were analyzed. The proportion of vaccinated individuals was significantly lower in RTX users than in RTX non-users (69.3% vs. 90.9%; P < 0.001). RTX use was associated with an increased risk of all-case death (adjusted odds ratio [aOR] 1.85, 95% confidence interval [CI] 1.39–2.46, P < 0.001). In the subgroup analysis for vaccinated individuals, the risk of SARS-CoV-2 infection was significantly greater for RTX users compared to non-users (aOR 2.48, 95% CI 1.02–6.04, P = 0.045), and RTX use was also associated with a significantly increased risk of hospitalization (aOR 3.79, 95% CI 1.28–11.23, P = 0.016) and all-case death (aOR 3.85, 95% CI 2.54–5.84, P < 0.001).

Conclusion

The use of RTX was associated with an increased risk of all-cause death in immunocompromised patients. Among vaccinated individuals, RTX users were at an increased risk of SARS-CoV-2 infection, as well as an increased risk for hospitalization of COVID-19 and all-cause death.

Disclosures

All Authors: No reported disclosures
173. Identifying Opportunities for Urine Culture Diagnostic Stewardship in a Pediatric Health System
Authors: Yoon Hee-won , Meyahnwi Didien , Chiotos Kathleen , Dunn Michelle , Green Rebecca , Ku Brandon , Mutucumarana Charmaine , Overland Maya , Polsky Tracey , Gwyneth Sharer , Smith Kenneth , Swami Sanjeev K , Same Rebecca
Published: January 2025

Background

Reflex urine cultures based on urinalysis (UA) parameters are commonly used to avoid excess urine cultures and reduce treatment of asymptomatic bacteriuria in adults. Reflex testing is less common in pediatrics and optimal UA parameters in children are unknown. We aimed to evaluate performance of laboratory and point of care (POC) UA for prediction of significant bacteriuria in children.

Methods

We performed a retrospective cohort study of all urine cultures performed in the emergency departments and inpatient units of two hospitals within a tertiary care children’s health system between January 2023 and March 2024. We identified core laboratory-performed UAs (macroscopic UA with reflex to microscopic UA for presence of blood, leukocyte esterase (LE), nitrite, or protein) and POC UAs performed within 48 hours of each culture to characterize diagnostic practices. We defined a negative culture as < 50,000 CFU/mL of bacteria or results consistent with contamination. Limiting analysis to UAs performed within 24 hours of a culture, we then determined the performance characteristics of POC and lab UA parameters for prediction of significant bacteriuria, using a threshold of ≥ 50,000 CFU/mL and ≥ 100,000 CFU/mL.

Results

There were a total of 10,115 urine cultures performed in 7,152 children (Table 1). There were 8,638 (85%) negative cultures. No UA was done in 2,019 (20%). Of cultures with a UA, 8,021 (99%) were done within 24 hours. Of 6,856 cultures with a lab UA, 4,828 (70%) had < 5 WBCs/hpf or no WBC reported due to negative macroscopic UA. Of these, 4,608 (95%) cultures were negative. At least 5 WBCs/hpf had a sensitivity of 86%, specificity of 55%, and negative predictive value (NPV) of 93.5% for growth of ≥ 50,000 CFU/mL in culture (Table 2). POC UA LE had similar sensitivity but lower specificity, positive predictive value (PPV), and NPV compared to lab UA. POC UA nitrite had higher sensitivity and similar specificity, PPV, and NPV compared to lab UA (Table 3).

Conclusion

Over 10,000 urine cultures were sent in a 15-month period. Pyuria had a high NPV for significant bacteriuria. Because 70% of lab UAs do not have pyuria, implementation of a reflex urine culture could eliminate many unnecessary urine cultures without significantly compromising detection of bacteriuria.

Disclosures

All Authors: No reported disclosures
175. Concordance of UTI Antibiotic Treatments with Facility-Specific Antibiograms in Nursing Homes
Authors: Langenstroer Madeline C , Jolles Sally , Crnich Christopher J , Jump Robin , Wilson Brigid , Bej Taissa A , Kowal Corinne , Hicks Oteshia , Taylor Lindsay , Multhauf Grace , Furuno Jon P , Santos Evita T , Shilling Hailey , Zhou Michelle H , Nace David A , Murillo Theresa N , Mangal Krishnendu
Published: January 2025

Background

Empiric antibiotic treatment of urinary tract infections (UTI) in nursing homes (NHs) is complicated by increasing antibiotic resistance. Antibiograms may enhance empiric antibiotic treatment decisions in this setting. We conducted a pilot study of a urine-specific antibiogram in 9 NHs in Oregon and Pennsylvania. The objectives of this study were to (1) characterize patterns of antibiotic resistance among uropathogens recovered from study NHs and (2) determine the concordance between antibiotic prescriptions and facility-specific antibiograms.Table 1.WISCA-Concordant Antibiotics across 9 NHs

Methods

We developed a facility-specific weighted incidence syndromic cumulative antibiogram (WISCA) using two years of urine culture results for each study NH. The WISCA conveyed the cumulative susceptibility of facility-collected uropathogens to 7 antibiotics in three susceptibility strata ( >90%, 80-89%, and < 80%). Data on antibiotic prescriptions for the empiric treatment of UTI during the 6-month pilot were abstracted from facility health records and entered into a REDCap database. Antibiotic prescriptions with a probability of activity exceeding the 80% susceptibility threshold were classified as WISCA-concordant.Figure 1.Concordance of Empiric Antibiotic Selection with Facility-Specific WISCAs

Results

WISCA susceptibility patterns varied considerably across NHs and regions (Table 1). On average, two oral antibiotic options with projected activity exceeding 80% were available in most Oregon NHs. In contrast, oral antibiotic options with activity exceeding 80% were uncommon in Pennsylvania NHs. Ceftriaxone and Ciprofloxacin were the only antibiotics with activity in these facilities. There were 173 empiric antibiotic treatments for UTI in study NHs during the pilot. A minority of the antibiotics chosen were concordant with the facility-specific WISCA (n = 69, 39.9%), although this varied by facility (Figure 1).

Conclusion

Our study demonstrates wide variability in antibiotic susceptibility of uropathogens at both the facility and regional levels. Antibiotics selected for the empiric treatment of UTI in study NHs were projected to have limited activity based on facility-specific WISCAs. Further studies to examine the factors influencing antibiotic choice and level of concordance with patient-specific culture results are ongoing.

Disclosures

Robin Jump, MD, PhD, Abacus: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support Jon P. Furuno, PhD, Merck & Co., Inc: Grant/Research Support
176. A Quality Improvement Endeavor to Improve Antibiotic Prescribing for Children with Acute Otitis Media in Emergency and Urgent Care Settings
Authors: Dimo Joana , Weber Matthew J , Birkholz Meghan C , Topoz Irina , Poole Nicole M
Published: January 2025

Background

Acute otitis media (AOM) self-resolves without antibiotics in 60-75% of cases. This study evaluates the impact of a quality improvement intervention on antibiotic prescribing for pediatric AOM.Figure 1.Proportion of antibiotics prescribed per all AOM diagnoses in patients 61 days to 18 years old.

Methods

A bundled intervention for AOM included (1) an electronic health record (EHR) order set that preselected a 5-day antibiotic duration for children 24 months and older (April 2021) and (2) creation of a local clinical care pathway (CCP) for AOM (December 2022). The CCP encouraged observation and pain management in children 24 months and older, as well as children 6-23 months with unilateral, non-severe AOM. A retrospective review of patients 61 days to 18 years old presenting to emergency and urgent care centers between January 2019 through September 2023 was conducted. Outcomes were (1) rates of antibiotic prescribing (enteral or ceftriaxone) in patients 61 days to 18 years old, (2) treatment duration of 5 or fewer days (excluding azithromycin) in patients 24 months to 18 years old, and (3) first-line antibiotic choice (amoxicillin) in patients 61 days to 18 years old. Statistical process control charts with upper and lower control limits and “special cause” variation by standard definitions were used to analyze outcomes.Figure 2.Proportion of patients with duration of 5 or fewer days compared to all duration in patients 2 years to 18 years old.

Results

A total of 34,324 patients were included. Rates of antibiotic prescribing remained high throughout the study (88 to 93%), with special cause variation detected (Figure 1). After EMR order-set development, increased compliance with recommended duration of 5 or fewer days was observed (3% to 83%), with special cause variation throughout the study (Figure 2). Rates of amoxicillin prescribing decreased throughout the study (77 to 74%), with special cause variation detected (Figure 3).Figure 3.Proportion of amoxicillin prescribed per all antibiotics in patients 61 days to 18 years old.

Conclusion

Implementation of an EHR order set resulted in shorter durations of prescribed antibiotics for AOM in patients older than 24 months. Antibiotic prescribing rates increased, and amoxicillin prescribing decreased throughout study period. The effect of the amoxicillin shortage, which started in October 2022, likely played a role in decreased amoxicillin prescribing rates. This project indicated that further dissemination of the new CCP and de-implementation of previous practices is needed to achieve improvement in antibiotic prescribing and first line antibiotic use.

Disclosures

All Authors: No reported disclosures
177. AMR-Informed Antibiotic Use Metrics
Authors: Goodman Reid , Bewley Alice , Atkinson Andrew , Fraser Victoria J , Vazquez Guillamet M Cristina
Published: January 2025

Background

Antimicrobial resistance (AMR) poses a significant public health threat, and efforts are underway to monitor and reduce unnecessary antibiotic usage. The Standardized Antibiotic Administration Ratio (SAAR) measures unit and hospital consumption of antibiotics by adjusting for facility characteristics. However, SAAR currently does not consider the prevalence rates of AMR that could justify or challenge antibiotic usage. Our objective is to develop an optimization function that identifies the best antibiotic choice for sepsis caused by Gram-negative bacilli (GNB). Optimization functions determine the optimal solution given specific constraints.

Methods

This observational cohort study included all adult patients meeting the CDC sepsis criteria and admitted to any of the 10 BJC acute care hospitals between 2016 and 2021. We focused on GNB isolated from clinical cultures, specifically the 17 most common species. We selected 15 commonly used antibiotics with activity against GNB (Table 1). Initially, we calculated the antibiotic weights to determine the relative coverage of each antibiotic, expressed as the ratio of GNB susceptible to all cultured GNB. The optimization function then constrained the optimal choice to the antibiotic with the lowest weight that still exhibited activity against the ultimately isolated strain. The resulting optimal antibiotic weights were averaged per hospital and study year and reported as a ratio to the weights of antibiotics used, akin to SAAR.

Results

Our study included 11,515 GNB cultures obtained from 9,531 patients. GNB were isolated from urine (40.5%), blood (20.5%), and respiratory specimens (20.3%). We present the antibiotic weights in Table 1, along with the representative ratios of empiric and directed observed-to-optimal antibiotic weights across BJC hospitals during the study period (Figs 1 and 2). Additionally, we contrast the SAAR trends for the same hospitals in Fig. 3.

Conclusion

Our optimization function selects the narrowest spectrum antibiotic and facilitates comparisons in antibiotic spectrum usage while considering existing AMR dynamics. It provides actionable insights and complements SAAR's metric of antibiotic duration.

Disclosures

M Cristina Vazquez Guillamet, MD, BNGO: Stocks/Bonds (Public Company)|Carisma Therapeutics: Stocks/Bonds (Public Company)|Ocugen: Stocks/Bonds (Public Company)