bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Varicella Zoster Virus (VZV) in Central Nervous System Infectious Syndromes
Authors: Yakovenko Viktoria , Ciobotaro Pnina , Bardenstein Rita , Zusev Margalit , Zimhony Oren
Published: November 2024

Background: We describe the proportion of VZV infection in central nervous system (CNS) infectious syndromes in a single Israeli medical center.

Methods: An observational cohort study was conducted in Kaplan Medical Center (a secondary hospital, Israel) between July 1, 2014, and March 31, 2019. Included were adult patients (≥ 16 years old) with CNS infection with an aseptic CSF profile that were subjected to molecular tests for herpes viruses, HSV either 1 or 2, VZV, enteroviruses, and IgM for West Nile virus (WNV).

Results: Clinical presentation suggestive of CNS infection led to lumbar puncture and CSF analysis in 1500 patients yielding 178 cases with aseptic CSF profile. For 62/109 (55.9%) cases of meningitis, the etiology remained unknown, enterovirus accounted for 21 cases (18.9%), VZV for 16 (14.4%), and HSV 1 for 7 (6.3%). One case each of bacterial, fungal, and parainfluenza virus accounted for the other 3 cases. For 30/63 (47.6%) cases of encephalitis, the etiology remained unknown, HSV accounted for 11 cases (17.5%), VZV for 8 (12.7%), and WNV for 10 (15.9%); in two cases, enterovirus was identified and one case of influenza A and one of mycoplasma, accounted for the rest. In six patients with myelitis VZV was identified in 4 (66.7%). Notably, a typical herpetic rash was identified in only 11/28 (39.28%) of cases of VZV CNS infection.

Conclusions: VZV is a significant cause of viral CNS infections. In the majority of patients with neurologic syndrome and evident VZV there is no association with a typical herpetic rash. These results apply to Israeli population and likely to other populations with similar background of VZV past infections.
Using AI to Predict Patients’ Length of Stay: PACU Staff’s Needs and Expectations for Developing and Implementing an AI System
Authors: Lundsten Sara , Jacobsson Maritha , Rydén Patrik , Mattsson Lars , Lindgren Lenita
Published: November 2024

Introduction: The need for innovative technology in healthcare is apparent due to challenges posed by the lack of resources. This study investigates the adoption of AI‐based systems, specifically within the postanesthesia care unit (PACU). The aim of the study was to explore staff needs and expectations concerning the development and implementation of a digital patient flow system based on ML predictions.

Methods: A qualitative approach was employed, gathering insights through interviews with 20 healthcare professionals, including nurse managers and staff involved in planning patient flows and patient care. The interview data were analyzed using reflexive thematic analysis, following steps of data familiarization, coding, and theme generation. The resulting themes were then assessed for their alignment with the modified technology acceptance model (TAM2).

Results: The respondents discussed the benefits and drawbacks of the proposed ML system versus current manual planning. They emphasized the need for controlling PACU throughput and expected the ML system to improve the length of stay predictions and provide a comprehensive patient flow overview for staff. Prioritizing the patient was deemed important, with the ML system potentially allowing for more patient interaction time. However, concerns were raised regarding potential breaches of patient confidentiality in the new ML system. The respondents suggested new communication strategies might emerge with effective digital information use, possibly freeing up time for more human interaction. While most respondents were optimistic about adapting to the new technology, they recognized not all colleagues might be as convinced.

Conclusion: This study showed that respondents were largely favorable toward implementing the proposed ML system, highlighting the critical role of nurse managers in patient workflow and safety, and noting that digitization could offer substantial assistance. Furthermore, the findings underscore the importance of strong leadership and effective communication as key factors for the successful implementation of such systems.
A Phase III Randomized Trial of Integrated Genomics and Avatar Models for Personalized Treatment of Pancreatic Cancer: The AVATAR Trial
Authors: Sarno Francesca , Tenorio Jair , Perea Sofia , Medina Laura , Pazo-Cid Roberto , Juez Ignacio , Garcia-Carbonero Rocío , Feliu Jaime , Guillen-Ponce Carmen , Lopez-Casas Pedro P. , Guerra Carmen , Duran Yolanda , López-Acosta José Francisco , Alonso Carolina , Esquivel Estrella , Dopazo Ana , Akshinthala Dipikaa , Muthuswamy Senthil K. , Lapunzina Pablo , Bockorny Bruno , Hidalgo Manuel
Published: November 2024

Purpose:

Pancreatic ductal adenocarcinoma (PDAC) has limited treatment options. We compared the efficacy of comprehensive precision medicine against that of the conventional treatment in PDAC.

Patients and Methods:

We report a phase III trial of advanced PDAC in which patients were randomized (1:2) to a conventional treatment treated at physician’s discretion (arm A) or to precision medicine (arm B). Subjects randomized to arm B underwent a tumor biopsy for whole-exome sequencing and to generate avatar mouse models and patient-derived organoids for phenotypic drug screening, with final treatment recommended by the molecular tumor board. The primary objective was median overall survival (OS).

Results:

A total of 137 patients were enrolled with 125 randomized, 44 to arm A and 81 to arm B. Whole-exome sequencing was performed in 80.3% (65/81) patients of arm B, with potentially actionable mutations detected in 21.5% (14/65). Experimental models were generated in 16/81 patients (19.8%). Second-line treatment was administered to 39 patients in the experimental arm, but only four (10.2%) received personalized treatment, whereas 35 could not receive matched therapy because of rapid clinical deterioration, delays in obtaining study results, or the absence of actionable targets. The median OS was 8.7 and 8.6 months (P = 0.849) and the median progression-free survival was 3.8 and 4.3 months (P = 0.563) for the conventional and experimental arms, respectively. Notably, the four patients who received personalized treatment had a median OS of 19.3 months.

Conclusions:

Personalized medicine was challenging to implement in most patients with PDAC, limiting the interpretation of intention-to-treat analysis. Survival was improved in the subset of patients who did receive matched therapy.
Abstract B047: Monitoring treatment response and toxicity in BRAF V600-mutant metastatic melanoma with circulating cell-free DNA
Authors: Jain Sidharth S , Patrick IV McDeed A. , McNamara Megan E , Alley Amber R , Rosenstrauch Dori S , Sun Harry , Thompson Natalie , Kirkwood John M , Gibney Geoffrey T , Atkins Michael B , Wellstein Anton
Published: November 2024

Background: The DREAMseq trial (EA6134, NCT02224781) was a national multi-center randomized phase III trial coordinated by ECOG-ACRIN that found that immune checkpoint inhibitor (IO) treatment achieves improved survival outcomes compared to targeted therapy (TT) in patients with BRAF V600-mutant metastatic melanoma. Still, approximately 40% of patients do not respond to IO, and existing biomarkers fail to distinguish this subset of patients who do not benefit from IO therapy. Additionally, as many as 80% of patients may experience immune- related adverse events (irAEs), which range from mild dermatological symptoms to life- threatening myocarditis. Here, we explore the use of the methylation status of cell-free DNA (cfDNA) in serially collected blood samples to measure response and toxicity in the context of IO- and TT-treated metastatic melanoma. Methods: Serial serum samples were collected from patients with BRAF V600-mutant metastatic melanoma treated with ipilimumab/nivolumab (IO) or dabrafenib/trametinib (TT). Circulating cfDNA was isolated from serially collected serum samples, enriched for regions of interest by hybridization capture and sequenced using enzymatic methyl-seq. Cell-type deconvolution was performed to determine the abundance of cell type- specific methylation patterns of cfDNA molecules in patient serum at different time points of treatment. The BRAF V600 mutation abundance in total cfDNA was also assessed. Results: We identified melanocyte lineage-specific DNA methylation regions and demonstrate that the methylation status of these regions remains conserved in malignant melanoma. We characterized the changes in abundance of the melanocyte-lineage cfDNA over the course of treatment and show that these changes distinguish responders from non-responders to either IO or TT. Furthermore, we track the abundance of cell type-specific DNA from normal tissues to identify markers indicative of adverse effects or disease progression. Conclusions: We established melanocyte-lineage methylation markers and evaluated the use of cell-type specific DNA methylation to monitor treatment effects of immune checkpoint or BRAF/MEK inhibitors in metastatic melanoma using serially collected blood samples.

Citation Format: Sidharth S Jain, A. Patrick IV McDeed, Megan E McNamara, Amber R Alley, Dori S Rosenstrauch, Harry Sun, Natalie Thompson, John M Kirkwood, Geoffrey T Gibney, Michael B Atkins, Anton Wellstein. Monitoring treatment response and toxicity in BRAF V600-mutant metastatic melanoma with circulating cell-free DNA [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B047.
Abstract B067: Dynamic chromatin landscapes of colorectal cancer development and cell-free DNA fragmentation
Authors: Vulpescu Nicholas A. , Foda Zachariah H. , Wisse Pieter H.A. , Cherry Christopher , Medina Jaime E. , Adleff Vilmos , Fijneman Remond J.A. , Scharpf Robert B. , Meijer Gerrit A. , Carvalho Beatriz , Velculescu Victor E.
Published: November 2024

This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR016) of the Conference Program/Proceedings.

Citation Format: Nicholas A. Vulpescu, Zachariah H. Foda, Pieter H.A. Wisse, Christopher Cherry, Jaime E. Medina, Vilmos Adleff, Remond J.A. Fijneman, Robert B. Scharpf, Gerrit A. Meijer, Beatriz Carvalho, Victor E. Velculescu. Dynamic chromatin landscapes of colorectal cancer development and cell-free DNA fragmentation [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B067.
Abstract B068: Inferring enhancer activity from cell-free DNA fragmentation patterns
Authors: Yang Alexis
Published: November 2024

We present a framework for inferring enhancer activity from cell-free DNA (cfDNA) fragmentation patterns, offering a novel feature set for cfDNA analysis that reflects gene regulation. Enhancers are promoter-distal regulatory elements that regulate gene expression programs that define cell types and cellular states. Despite advances in inferring gene regulation in cancer using liquid biopsy, it remains challenging to identify signals of enhancer activity from cell-free DNA (cfDNA). Active enhancers are characterized by transcription of short enhancer RNAs (eRNAs). Recent studies demonstrated that cfDNA from promoters of transcribed genes demonstrates high variation in DNA fragment length, or “fragmentation entropy”. We tested whether eRNA transcription can be inferred based on cfDNA fragmentation entropy. We quantified “enhancer fragmentation entropy” (EFE) to profile enhancer activity in plasma by measuring Shannon entropy of cfDNA fragments around enhancer transcription start sites (TSS). Using PRO-cap data from lymphoblastoid cell lines, we analyzed EFE signals at 70,000 transcribed enhancers and observed distinct patterns between active (expressed) and inactive enhancers in cfDNA from healthy individuals. cfDNA from patients with prostate cancer showed elevated EFE at enhancers activated in prostate cancer. EFE at these sites correlated with circulating tumor DNA (ctDNA) levels in a published cfDNA dataset of 41 prostate cancer plasma samples. Lower-dimensional projections of the entropy signals across 300 “modules” of co-regulated enhancers revealed tighter clustering of samples within the same cancer type, suggesting that these entropy patterns capture cell-type specific enhancer activity. Our findings suggest that enhancer fragmentation entropy captures cell-type specific signals and, when measured at cancer-specific enhancers in cfDNA, could serve as a promising biomarker for cancer detection and monitoring. Ongoing work is focused on validating these findings in larger cohorts and applying EFE to cancer monitoring and clinical subtyping.

Citation Format: Alexis Yang. Inferring enhancer activity from cell-free DNA fragmentation patterns [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B068.
Abstract PR001: The CTC RPL/RPS gene signature: Targeting translation and the cell cycle inversely affects CTC metabolism but not metastasis
Authors: Marchetti Dario
Published: November 2024

Melanoma brain metastasis (MBM) is the most devastating consequence of melanoma, is increasing in frequency, and is linked to poor prognosis and dismal survival. By employing an unbiased, multipronged approach, we discovered a CTC gene signature for ribosomal protein large/small subunits (RPL/RPS) which associated with MBM onset and progression. Experimental strategies involved capturing, transcriptional profiling, and interrogating CTCs, either directly isolated from blood of melanoma patients at distinct stages of progression, from CTC-driven MBM in experimental animals, or by developing/applying the first MRI CTC- derived MBM xenograft model (MRI-MBM CDX) to discriminate MBM spatial and temporal growth, thus faithfully recreating its clinical presentation. Accordingly, we hypothesized that targeting CTC ribogenesis can prevent melanoma metastasis in general, MBM in particular. We treated CDX cohorts with FDA-approved protein translation inhibitor omacetaxine in the presence or absence of CDK4/CDK6 inhibitor palbociclib, and monitored metastatic development and cell proliferation. Necropsies and IVIS imaging showed decreased MBM/extracranial metastasis in drug-treated mice, and RNA-Seq on mouse-blood-derived CTCs revealed downregulation of four RPL/RPS genes of the CTC signature. Notably, by performing the first-ever functional metabolic characterization of circulating neoplastic cells/CTCs in real- time, coupled with confirmatory RT-qPCR, we found that omacetaxine and palbociclib inversely affected glycolytic metabolism, and demonstrated that dual targeting of cell translation and proliferation is critical to suppress plasticity in metastasis-competent CTCs. This study identifies the relevance of targeting the CTC RPL/RPS signature to suppress melanoma metastasis, and set forward notions for novel therapies to affect metastasis by the deregulation of translation controlling CTC states. Studies involving structural and mechanistic analyses of CTC dormant vs active ribosomes by cryogenic electron microscopy are in progress.

Citation Format: Dario Marchetti. The CTC RPL/RPS gene signature: Targeting translation and the cell cycle inversely affects CTC metabolism but not metastasis [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr PR001.
Table 2 from Genomic Features of Newly Diagnosed Large B-cell Lymphoma with or without Subsequent Disease Progression
Authors: Landsburg Daniel J. , Morrissette Jennifer J.D. , Nasta Sunita D. , Barta Stefan K. , Schuster Stephen J. , Chong Elise A. , Svoboda Jakub , Barlev Ashley , Bagg Adam , Priore Salvatore F.
Published: November 2024

Percentage of genomic alterations in progression cases
Post-Asphyxial Aftercare and Management of Neonates in Low- and Middle-Income Countries: A Systematic Evidence Synthesis
Authors: Muralidharan Oviya , Rehman Sarah , Sihota Davneet , Harrison Leila , Vaivada Tyler , Bhutta Zulfiqar A.
Published: November 2024

Introduction: Effective post-resuscitation care is crucial for improving outcomes in neonates post-asphyxia. This review aimed to provide a comprehensive overview of post-asphyxial aftercare strategies and forms part of a supplement describing an extensive synthesis of effective newborn interventions in low- and middle-income countries (LMICs). Methods: Evidence was generated by performing de novo reviews, updates to reviews via systematic searches, and reanalyses of studies conducted in LMICs from existing reviews. Results: Sixty-one trials recruiting 5,046 term infants post-asphyxia were included across all intervention domains. Limited studies were available from LMICs related to fluid restriction, antiseizure medications, and early interventions to improve developmental outcomes. Our reanalysis of whole-body cooling trials in LMICs found effects on neonatal mortality and mortality or neurological disability in infancy differed significantly based on the care center and type of cooling device used. Pharmacological therapies for neuroprotection evaluated in 27 trials in middle-income countries had varied effects in neonates with encephalopathy. Majority of the trials (60%) focused on magnesium sulfate therapy and showed significant improvements in short-term mortality and morbidities. Conclusion: The sample sizes of included trials were relatively small, and the certainty of evidence ranged from very low to moderate. Evidence on long-term survival and neurodevelopmental outcomes was limited. Further research on promising neuroprotective therapies and factors affecting their implementation in low-resource contexts is required. To reduce the high burden related to asphyxia in LMICs, this review underscores the need for a paradigm shift toward prevention, and strategies that emphasize improving antenatal and obstetric care.
Worldwide Burden of Retinoblastoma from 1990 to 2021
Authors: Feng Yaling , Feng Xiaoyi , Lv Yun
Published: November 2024

Introduction: The aim of the study was to report the global, regional, and national burden of retinoblastoma between 1990 and 2021, by age, sex, and sociodemographic index (SDI). Methods: We leveraged the Global Burden of Disease 2021 Study to elucidate the epidemiological landscape of retinoblastoma, encompassing prevalence, incidence, mortality, and disability-adjusted life years (DALYs) across 204 nations and territories spanning the period from 1990 to 2021. The SDI was employed to evaluate the interplay between socioeconomic development and the burden of retinoblastoma. Results: In 2021, global estimates unveiled 57,333 prevalent cases of retinoblastoma, yielding 6,274 incident cases, 2,762 deaths, and 243,204 DALYs. Globally, the age-standardized prevalence, incidence, mortality, and DALY rates for retinoblastoma in 2021 were 0.86, 0.09, 0.04, and 3.65 per 100,000 population, respectively. Tokelau, Kenya, and Portugal demonstrated the highest age-standardized prevalence and incidence rates of retinoblastoma in 2021. The global prevalence of retinoblastoma peaks among children aged 2–4 years and subsequently declines with increasing age. At the regional level, the correlation between SDI and age-standardized prevalence rates for retinoblastoma manifested a V-shaped pattern. Conclusions: This comprehensive examination of retinoblastoma epidemiological trends underscores the imperative for heightened vigilance and more efficacious therapeutic interventions, especially within resource-limited environments. The findings accentuate the need for targeted strategies to address the disparate burden of retinoblastoma across diverse socioeconomic landscapes.
Impact of Sublethal Disinfectant Exposure on Antibiotic Resistance Patterns of Pseudomonasaeruginosa
Authors: Al-Jebouri Mohemid Maddallah
Published: November 2024

Objective: The problem of hospital cross-infection due to contamination of disinfectants has been recognized elsewhere. The passage of bacteria through diluted disinfectants may not only bring about phenotypic changes in their antibiograms but also changes in phage susceptibility patterns. Contact with disinfectants in sublethal concentrations allows survival and multiplication of bacteria. Methods and Materials: Serial passage, through disinfectants at subminimal inhibitory concentrations, induced antibiotic resistance in 18% of derived phenotypic variants of fifty strains of Pseudomonas aeruginosa which were isolated from diarrheal stools of infants in children’s hospital. Results: A proportion of these strains became susceptible to an increased number of antibiotics. The present study revealed that all the isolates were resistant to tetracycline and carbenicillin and 40% of these isolates became sensitive to both antibiotics after exposure to disinfectants. The exposure to disinfectants induced neomycin resistance among two isolates. The resistance patterns were three before disinfectants exposure which increased to be nine different patterns after exposure. No antibiotic resistance was transferred between P. aeruginosa and Escherichia coli K12 as a recipient strain. Conclusions: Almost 50% of the isolates tested became sensitive to tetracycline, carbenicillin and co-trimoxazole after exposure to disinfectants. The resistance patterns among the 50 isolates were three which changed to be nine different patterns after exposure to disinfectants. Unjustifiable use of disinfectants might give a chance for survival and multiplication of pathogenic bacteria to develop new resistance patterns to antibiotics in use with a short time. These new resistance variants of bacteria which multiply in hospital environment could lead to serious epidemic conflicts particularly the epidemiological reporting and management.
Next-Generation Sequencing in Diagnosis of Monogenic Cholestatic Liver Disorders: A Single-Center Experience
Authors: Demir Engin , Bulut Fatma Derya , Bilginer-Gürbüz Berrak , Döğen Mehmet Ercüment , İşlek Ali , Mermer Serdar , Başer Burak , Ürel-Demir Gizem
Published: November 2024

Introduction: Cholestasis in childhood is a rare clinical condition, yet a definitive diagnosis is crucial for initiating treatment of these curable diseases and preventing related morbidity and mortality. The most common cause of infant cholestasis is biliary atresia (25–40%), followed by monogenic cholestatic diseases (25%), metabolic diseases (20%), and cryptogenic cholestasis. This study focuses on assessing the clinical utility of next-generation sequencing (NGS) panels, including clinical exome sequencing and whole exome sequencing, in diagnosing cholestatic diseases when the etiology cannot be elucidated through conventional methods. Materials and Methods: We conducted a retrospective examination of pediatric patients who sought care at a single-center pediatric gastroenterology department between August 2020 and March 2022 and were diagnosed with cholestasis. A total of 36 patients underwent a thorough investigation to rule out infectious, toxic, metabolic, structural, chromosomal, and endocrine causes. Patients whose diagnoses were established through traditional investigations were excluded from the study. The remaining 14 patients underwent either whole exome sequencing or targeted NGS methods. Results: A definitive diagnosis was achieved for 12 patients, while 2 patients remained undiagnosed despite comprehensive genetic examinations. The most commonly encountered diseases in this cohort were progressive familial intrahepatic cholestasis, linked to mutations in the ABCB11, ATP8B1, and TJP2 genes, as well as Dubin-Johnson syndrome associated with ABCC2 mutations. NGS demonstrated a diagnostic accuracy of 85.7% in patients for whom a diagnosis could not be established through extensive traditional workup. Conclusion: NGS emerges as a valuable diagnostic tool in cases of cholestasis where traditional methods fall short in providing a definitive diagnosis. Moreover, our study unveiled three previously undocumented variants in the ABCB11 [c.1165G>C; p.(Ala389Pro) and c.783 + 1G>A] and ABCC2 [c.4246_4247del; p.(Lys1416ValfsTer46)] genes.
Disfunção Cardíaca Associada À Quimioterapia Em Paciente Pediátrico: Relato De Caso
Authors: Adriano Maryanne Pereira Franco , Fernandes Luanna Albuquerque , Arruda Isabela Tatiana Sales , Quintans Ynnaiana Navarro de Lima Santana , Martins Jessica Laureano
Published: November 2024

Introduction: Due to advances in antineoplastic treatments, there has been a notable improvement in the outlook of cancer patients. However, it is crucial to highlight that the cardiotoxicity associated with these therapeutic approaches is recognized as one of the most significant adverse effects. This phenomenon is characterized by the ability of chemical agents or therapeutic procedures to induce damage to the heart muscle, resulting in compromised cardiac function. Objectives: To present a case report of a patient suffering from Non-Hodgkin's Lymphoma (NHL), with impaired cardiac function due to cardiotoxicity. Methods: This is a descriptive observational study, of the case report type, which describes the clinical manifestations and management of a patient with cardiac dysfunction associated with chemotherapy. The research data used were collected through medical records made available by the public health service reference in pediatric oncology in the city of João Pessoa-PB. Results: Report the case of an 18-year-old pediatric patient, diagnosed with non-Hodgkin's Lymphoma, presenting with underlying heart disease, who underwent chemotherapy treatment, developing cardiotoxicity that led to death. Conclusion: Therefore, it is essential that continuous monitoring is implemented throughout the entire cancer treatment. Additionally, it is necessary to ensure that patients have broad access to diagnostic tests and chemotherapy with a cardioprotective profile, aiming to minimize the risk of cardiotoxicity. These measures are essential to reduce the incidence of adverse effects on the myocardium and improve the safety and effectiveness of oncological treatment.
Desafios diagnósticos e terapêuticos dos transtornos de ansiedade em comorbilidade com o transtorno do espectro Autista: uma revisão integrativa
Authors: Araújo Manuela , Monteiro Maria do Rosário Nascimento e Sousa de Bessa
Published: November 2024

Anxiety Disorders are common in children and youth with Autism Spectrum Disorder (ASD), affecting 16-40% of cases and exacerbating functional impairment by amplifying problematic behaviours such as deficits in social skills and repetitive behaviours. The article aims to explore the interaction between ASD and Anxiety Disorders, with a focus on prevalence, diagnosis, and treatment. A literature review was conducted using databases such as Medline/PubMed, highlighting the clinical implications for managing these comorbidities. Psychopathology assessment is complex, considering underlying challenges in ASD, including atypical non-verbal responses and limitations in emotional expression, as well as the frequent overlap between anxiety and ASD symptoms. Additionally, anxiety symptoms may deviate from conventional criteria in psychopathological diagnostic manuals. Differential diagnosis between ASD and Social Anxiety is challenging due to similar symptoms. There is a demand for specific therapeutic approaches, such as modified cognitive-behavioural therapy, incorporating emotional recognition and social skills training. Pharmacological interventions require caution due to limited studies on SSRIs and potential side effects in individuals with ASD.
Abstract 4135303: Acute Pericarditis Secondary to Secukinumab Therapy
Authors: Jain Aakriti , Arora Sahej , Jawaid Hafsa , ahmed asmaa , Sharif Muhammad Hammad , VERGHESE BASIL , BAIBHAV BIPUL
Published: November 2024

Background:
Pericarditis is the most common pericardial disease worldwide and has a high recurrence rate of 15-30%. It is primarily idiopathic but can arise from infectious and non-infectious causes; drug related cases are rare. Secukinumab, a fully human anti-interleukin-17A monoclonal antibody used for treating psoriasis, has been identified through the FDA Adverse Event Reporting System as potentially inducing pericarditis, though literature is scant. We report a case of acute pericarditis related to secukinumab use.

Case presentation:
A 28-year-old male with history of psoriasis on secukinumab therapy presented with sharp, central chest pain, and progressive shortness of breath for 3 weeks. He was evaluated for similar chest pain 3 weeks prior; CT chest showed small pericardial effusion and he was managed with analgesics without improvement. This admission, he had tachycardia, and ECG showed sinus rhythm with diffuse ST elevation and PR depression (Figure 1A). Troponin I levels were normal and inflammatory markers were elevated. Transthoracic echocardiogram (TTE) revealed a large pericardial effusion without tamponade physiology (Figure 1B). CT chest confirmed large pericardial effusion, increased in size compared to CT done 3 weeks prior (Figure 2). He was diagnosed with pericarditis and started on ibuprofen and colchicine which improved his symptoms. Search for viral etiology including testing for COVID, influenza A and B, RSV, hepatitis and HIV were negative. Immunological workup for ANA and rheumatoid factor was negative. Thus, secukinumab was thought to be the likely culprit. Follow-up TTE in 3 months showed resolution of pericardial effusion.

Conclusion:
This case underscores the importance of considering medication-induced pericarditis in patients presenting with typical symptoms, especially when on treatment with drugs like secukinumab. Given the growing evidence from pharmacovigilance databases and the severe potential outcomes of untreated pericarditis, clinicians should maintain vigilance for such adverse effects. Further research is warranted to clarify the mechanisms by which secukinumab may contribute to pericardial inflammation in order to optimize management strategies in affected patients.
Abstract 4137177: A pharmacovigilance investigation from the FAERS database on patients using pembrolizumab and its association with cardiac arrhythmias
Authors: Upreti Prakash , Jancic Predrag , Milutinovic Stefan , Rathore Azeem , Nassar Sameh , Karki Roshan , Rao Mohan , Patel Brijesh
Published: November 2024

Background:
Arrhythmia is always a concern in oncological treatments. The advent of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, enhancing the immune system's ability to combat malignancies. They are being more frequently used, revealing a range of immune-related adverse events (irAEs). This study aims to investigate the incidence of cardiac arrhythmias in patients receiving Pembrolizumab.

Methods:
We conducted a retrospective analysis of the FDA Adverse Event Reporting System (FAERS) database, focusing on reports submitted between 2006 to 2024. Cases involving patients treated with ICs were identified, and information related to cardiac arrhythmias was extracted using the Medical Dictionary for Regulatory Activities (MedDRA). Patients ≥ 18 years of age treated with ICIs were included in this study. A disproportionality analysis was conducted to identify arrhythmia events associated with pembrolizumab by comparing it with other immune checkpoint inhibitors (nivolumab, ipilimumab, and atezolizumab) and the entire FAERS database using the reporting odds ratio (ROR) and information component (IC).

Results:
A comprehensive analysis of 61,236 reported cases of pembrolizumab use revealed a total of 3,901 cases with cardiac complications. Among these, 672 cases (17.22 %) of arrhythmias were reported, with 452 individuals (67.26%) requiring hospitalization and 172 cases (25.59%) resulting in fatalities.

Atrial fibrillation emerged as the most prevalent arrhythmia (49.7%). The occurrence of ventricular tachycardia with an ROR of 1.67 (1.18–2.35) and an IC of 0.44 (0.01–1.46) and complete atrio-ventricular block with an ROR of 1.57 (1.19–2.08) and an IC of 0.40 (0.04–1.24) were statistically significant. The reported arrhythmias associated with pembrolizumab are tabulated in
Table 1
. The majority of events were reported in males, as shown in
Figure 1
.

Conclusion:
This research offers significant insights into the connection between ICIs and cardiac arrhythmias, utilizing real-world data from the FAERS database. Healthcare providers should monitor cardiac events in patients receiving ICIs and aim to achieve a balance between anticancer effectiveness and cardiovascular safety. Further investigation is necessary to better understand the underlying mechanisms of arrhythmia and enhance risk stratification strategies for this specific patient group.
Abstract 4138067: Prognostic effect of echocardiography-assessed coronary flow reserve in heart failure with preserved ejection fraction
Authors: Cui Xiaotong , Wang Yanyan , Liu Dan , Xu Yamei , Zhao Yingjie , Song Yu , Han Xueting , Yuan Shuai , Yao Shun , Yu Xueting , Xie Zhonglei , wang zimu , Chen Haiyan , SHU XIAN HONG , hu kai , Zhou Jingmin , Ge Junbo
Published: November 2024

Background:
Coronary microvascular dysfunction (CMD) has been found common in patients with heart failure (HF) with preserved ejection fraction (HFpEF). The simplest and most feasible method for evaluating CMD is to measure coronary flow reserve (CFR) using echocardiography.

Hypothesis:
Whether the echocardiography-assessed CFR could predict the outcome in HFpEF patients is still unknown.

Aims:
We designed a prospective cohort study to investigate the prognostic effect of echocardiography-assessed CFR in HFpEF.

Methods:
Between December 2021 and April 2024, confirmed hospitalized HF patients with left ventricular ejection fraction (LVEF) ≥40% in Zhongshan Hospital Fudan University (Shanghai, China) were prospectively and consecutively enrolled. During index hospitalization, patients underwent the adenosine-based transthoracic Doppler echocardiography to evaluate the CFR of the left anterior descending branch. Treatments were given according to guidelines. Follow-up after discharge was carried out at outpatient or by telephone call. The primary endpoint was all-cause mortality.

Results:
A total of 176 HFpEF patients (111 males, mean age 66.8 ± 11.8 years old) were included. Median follow-up time was 290 days. Totally 93 patients (52.8%) demonstrated CFR <2.5, which is the classical CMD diagnostic threshold. However, CFR=2.5 had no significant discriminative ability in predicting mortality in this HFpEF cohort. Then the receiver operating characteristic curve combined with Youden's index were performed and indicated CFR=1.72 as the cut-off value to predict all-cause mortality. So patients were divided into two groups by CFR <1.72 (n=28) and CFR ≥1.72 (n=148). Compared with patients with CFR ≥1.72, HFpEF patients with CFR <1.72 were more likely to have atrial fibrillation, had higher level of high sensitive Troponin T, NT-proBNP, urinary albumin to creatinine ratio, and lower level of reactive hyperemia index measured by EndoPAT. During follow-up, 4 and 3 patients died in CFR < or ≥ 1.72 group, respectively (14.3% vs. 2.0%, P=0.013). Kaplan-Meier curves showed that patients with CFR <1.72 had poorer survival rate (Log-rank P=0.003). HFpEF patients had much higher risk in all-cause mortality if CFR <1.72 (hazard ratio 7.873, 95% CI 1.683-36.840) after adjusted for age, sex, NYHA class and LVEF.

Conclusions:
Lower level of echocardiography-assessed CFR obtained in hospitalization was associated with higher risk of all-cause mortality after discharge in HFpEF patients.
Abstract 4138093: Impact of Pre-Existing Cardiovascular Diseases on Severe Maternal Morbidity and Mortality During Delivery in Pregnant Women with Atrial Fibrillation
Authors: Yeo Yong Hao , San Boon Jian , Ong Tze Ern , Tan Min Choon , Tamirisa Kamala , Mehta Nishaki
Published: November 2024

Background:
While the incidence of atrial fibrillation (AF) among pregnant women is increasing, the impact of pre-existing cardiovascular disease (CVD) on pregnant women with AF is not well-described in a large national database.

Objective:
This study aimed to compare pregnancy outcomes between those with AF alone and those with AF and pre-existing CVD categorized by the modified World Health Organization classification (mWHO).

Methods:
We used the Nationwide Readmissions Database and included all pregnant women with AF (2017-2020). We categorized the cohort into two groups depending on the presence of pre-existing CVD. We assessed the risk of severe maternal morbidity and mortality (SMM) outcomes, as defined by the CDC, between pregnant women with AF alone and those with AF and pre-existing CVD.

Results:
Out of the total 2,348 pregnant women with AF, 348 (14.8%) had pre-existing CVD. 69 (19.8%) had mWHO I- II CVD, 150 (43.1%) had mWHO II/III- IV CVD, and 129 (37.1%) had CVD not classified in mWHO. Overall, those with pre-existing CVD had higher rates of SMM/death (28.2% vs. 11.1%, P<0.01), non-transfusion SMM/death (25.9% vs. 9.8%, P<0.01), and cardiac SMM/death (21.6% vs. 5.5%, P<0.01) than those with AF alone. After adjustment, those with pre-existing mWHO I- II CVD and AF were not associated with higher odds of SMM/death (aOR: 0.81, 95% CI: 0.34-1.92, P=0.64), non-transfusion SMM/death (aOR: 0.45, 95% CI: 0.14-1.46, P=0.18), and cardiac SMM/death (aOR: 0.55, 95% CI: 0.13-2.30, P=0.41) than those with AF alone. Patients with pre-existing mWHO II/III- IV CVD and AF had higher odds of SMM/death (aOR: 7.21, 95% CI: 4.94-10.53, P<0.01), non-transfusion SMM/death (aOR: 7.38, 95% CI: 5.03-10.82, P<0.01), and cardiac SMM/death (aOR: 12.02, 95% CI: 7.99-18.10, P<0.01) than those with AF alone. Patients with pre-existing CVD not classified in mWHO and AF did not have higher odds of SMM/death (aOR: 1.64, 95% CI: 0.99-2.71, P=0.06) but had higher odds of non-transfusion SMM/death (aOR: 1.77, 95% CI: 1.06-2.97, P=0.03) and cardiac SMM/death (aOR: 1.96, 95% CI: 1.05-3.67, P=0.04).

Conclusion:
Compared to pregnant women with AF alone, those with pre-existing mWHO II/III- IV CVD and AF were associated with worse SMM/death, non-transfusion SMM/death, and cardiac SMM/death. However, similar findings were not noted in those with pre-existing mWHO I- II CVD and AF pregnant women.
Abstract 4138101: CAR-T-associated Cardiovascular Events are Associated with Increased Resource Utilization
Authors: Song Justin , Vuong Jacqueline , Mead Monica , Gornbein Jeffrey , Rothberg Michael , Pan Chelsea , Dhaliwal Jasmeet , Boiarsky Jonathan , Gaut Daria , Eradat Herbert , Schiller Gary , DEVOS SVEN , Timmerman John , Stein-Merlob Ashley , Neilan Tomas , Larson Sarah , Young Patricia , Mahmood Syed , Yang Eric
Published: November 2024

Background:
Chimeric antigen receptor T-cell (CAR-T) therapy targeting CD-19 utilizes ex-vivo engineered T-cells to treat refractory malignancies. Widespread CAR-T adoption is limited by resource utilization and cost, and CAR-T has also been associated with adverse cardiovascular events. Limited data exist exploring the relationship between CAR-T-associated cardiovascular events and resource utilization events (RUE).

Objective:
To evaluate whether CAR-T-associated cardiovascular events are associated with RUE.

Methods:
Records of patients treated with an FDA-approved CAR-T product between 2018 and 2022 at a single institution were reviewed. Cardiovascular events post-CAR-T were defined as arrhythmia, acute coronary syndrome, stroke, cardiovascular death, new cardiomyopathy, heart failure, or pericarditis. RUE was a composite of intensive care unit (ICU) transfer, prolonged length of stay (LOS; >75th cohort percentile), and unplanned 6-month readmission.

Results:
Of 117 patients, 30 (26%) experienced cardiovascular events over a median 16 (IQR 7-34) months follow-up. RUE occurred in 65 patients (56%): 28 (24%) ICU transfers, 23 (20%) prolonged LOS, and 48 (41%) readmissions. Those with RUE experienced subsequent higher mortality (62% vs. 21%, p≤0.001). Among patients who experienced cardiovascular events, 24 (80%) experienced RUEs. In a Cox model, cardiovascular events (HR 2.3, 95% CI 1.3-4.1) and high cancer burden (HR 2.1, 95% CI 1.3-3.5) were independently associated with increased RUE rate, after adjusting for age, Cytokine Release Syndrome grade ≥2, atrial fibrillation history, and CAR-T costimulatory domain.

Conclusion:
CAR-T recipients who experience cardiovascular events also experience increased resource utilization events. Further prospective studies are needed to assess whether post-CAR-T cardiovascular event management and/or pre-therapy assessment may reduce resource utilization burden.
Abstract 4138107: Ventricular Tachycardia Mortality Trends in Oncology: Where Are We Now?
Authors: Yeo Yong Hao , San Boon Jian , Tan Min Choon , Ang Qi Xuan , Lee Justin , Mehta Nishaki
Published: November 2024

Background:
Advancements in chemotherapeutic modalities lead to improved cancer survival rates. While the cardiotoxicity related to the therapies is increasingly recognized, real-world data on ventricular tachycardia (VT) mortality among them is limited.

Objective:
This study sought to determine the longitudinal cardiovascular mortality trends related to ventricular tachycardia in the cancer population.

Methods:
We queried the CDC WONDER database among patients ≥ 25 years old from 1999 to 2020. Cardiovascular disease was listed as the main cause of death, while VT and cancer were listed as contributing causes of death. We calculated age-adjusted mortality rates (AAMR) per 1,000,000 individuals. We determined the trends over time by estimating the annual percent change (APC) using the Joinpoint regression program.

Results:
In the study period, there were 3,483 cardiovascular mortalities related to ventricular tachycardia in patients with comorbid cancer. The overall AAMR decreased significantly from 1.28 (95% CI, 1.11-1.44) in 1999 to 0.67 (95% CI, 0.57- 0.77) in 2020, with an average APC of -2.91 (95% CI, -3.95, -1.86). Overall, males had higher AAMR than females (1.25 [95% CI, 1.20 – 1.30] vs. (0.36 [95% CI, 0.34 – 0.39]). African Americans and White patients have comparable AAMR of 0.78 (95% CI, 0.69-0.86) and 0.77 (95% CI, 0.74-0.80), respectively, which were higher than Asians (0.34 [95% CI, 0.25-0.44]) and Hispanics (0.33 [95% CI, 0.27-0.40]). The AAMR was higher in the rural region than in the urban region (0.72 [95% CI, 0.69 – 0.75] vs. 0.76 [95% CI, 0.70 – 0.81]). The West region had the highest AAMR (0.79 [95% CI, 0.74 – 0.85]).

Conclusion:
Cardiovascular mortality related to VT in patients with comorbid cancer dropped significantly throughout the years. Further targeted approaches are needed to address the disparities in sex, race, and region.
Abstract 4138211: A Machine Learning-Based Novel Risk Score Model for Takotsubo Cardiomyopathy
Authors: Agrawal Ankit , bhagat umesh , Haroun Elio , Arockiam Aro Daniela , Majid Muhammad , Wang Tom Kai Ming
Published: November 2024

Background:
Takotsubo cardiomyopathy (TC) is defined by acute but typically reversible left ventricular systolic dysfunction, typically precipitated by profound emotional or physical stress. Due to the scarcity of a prognostic scoring system for TC, we aimed to develop a novel machine learning-based risk score model to predict in-hospital mortality in TC patients.

Methods:
The National Inpatient Sample (NIS) 2016-2020 database was used to identify all adult patients (≥18 years of age) with TC, using ICD-10 code I51.81. Relevant clinical characteristics and outcomes were extracted. The primary endpoint was in-hospital all-cause mortality. The dataset was randomly split into 3 subsets: training, validation, and testing, with a ratio of 0.7, 0.2, and 0.1, respectively. The risk score was generated using the Autoscore package in R software, a machine learning-based tool for automatic clinical score generation. The performance was evaluated using the area under the receiver-operative characteristics curve (AUC) with 95% confidence intervals (95%CI).

Results:
Among the 38,662 TC patients identified [age 67.1±14.1 years, female 32,089 (83%)], there were 2499 (6.4%) primary outcome events. Out of the top 20 covariates seen in the Parsimony plot, we used eight for our risk score (0–127): age, comorbidity burden, cardiac arrest, cardiogenic shock, race, acute kidney injury, hypertension, and cardiac arrhythmia (Figure 1A). The AUC for the derivation and validation cohorts was 0.809 (0.780–0.837) and 0.838 (0.820–0.856), respectively (Figures 1B and 1C).

Conclusion:
We developed and internally validated a machine learning based-risk score model to predict outcomes in TC patients, achieving a high AUC of 0.838 (0.820-0.856). Risk score models guide risk stratification and management, and large future studies are needed to externally evaluate our results.
Abstract 4138824: Late Gadolinium Enhancement in the Basal Left Ventricle is Associated with Ventricular Arrhythmias in Patients with Pathogenic Titin Variants
Authors: Laws James , Varghese Bibin , Virk Zain , Togashi Daisuke , El-Harasis Majd , Shabani Mahsima , Pelphrey Cassady , Lancaster Megan , Grauherr Dakota , Williams Hollie , crawford diane , Sun Lili , Ye Fei , Kannankeril Prince , Kanagasundram Arvindh , Richardson Travis , Tandri Harikrishna , Yoneda Zachary , Stevenson Lynne , Roden Dan , Stevenson William , Dendy Jeffrey , Shoemaker BEN
Published: November 2024

Introduction:
Pathogenic titin (
TTN
) variants are associated with malignant ventricular tachycardia (VT) that often arises from fibrosis in the basal LV and may occur before severe LV systolic dysfunction. Late gadolinium enhancement (LGE) can identify the substrate for VT, but measurement of LGE in the basal LV is technically challenging. As genetic testing identifies more patients with earlier stages of
TTN
cardiomyopathy, methods are needed to stratify their risk for malignant VT.

Hypothesis:
LGE burden in the basal LV is greater in patients with pathogenic
TTN
variants compared to controls, and is associated with a higher risk of malignant VT.

Methods:
Patients with early-onset AF and/or ventricular arrhythmias (VAs) unrelated to ischemic heart disease underwent genetic sequencing. Cases had pathogenic or likely-pathogenic (P/LP) rare
TTN
variants. Controls had no P/LP variants in cardiomyopathy or arrhythmia genes and were matched by age, sex, and whether they had predominately AF or VAs. Cardiac MRIs were reanalyzed by two readers blinded to case/control status. Basal LV LGE was quantified using the 5-SD signal intensity method of 3 short axis segmented inversion recovery images 8mm apart beginning at the first segment below the LVOT. Risk of malignant VT was defined as: Low Risk (≤100 PVCs per day, no NSVT, no VT), Moderate Risk (NSVT or >100 PVCs per day), or High Risk (prior sustained VT).

Results:
There were 16
TTN
cases and 17 controls. Age (
TTN
53 years [Q1-Q3: 49-59]; controls 51 years [42-59]) and LVEF (
TTN
56% [49-62]; controls 60% [55-63]) were similar. Reanalysis identified basal LGE (defined as ≥5% burden) in 14 patients (42%) compared to only 7 (21%) in the original clinical reports. LVEF was >50% in 10 of 14 patients with LGE.
TTN
cases had significantly higher basal LGE burden compared to controls (
TTN
9.0% [4.8-13.5] vs. controls 1.4% [0.0-2.3], p<0.01). High and Moderate Risk groups for malignant VT had significantly more basal LV LGE compared to the Low Risk group (High Risk: N=2, median 16.1% [15.3-16.9]; Moderate Risk: N=9, 10.0% [5.9-13.4]; Low Risk: N=22, 2.1% [0.0-3.7] p=0.01).

Conclusion:
Among patients with relatively preserved LV systolic function, pathogenic
TTN
variants were associated with greater burden of LGE in the basal LV compared to controls, and basal LGE was associated with severity of ventricular arrhythmias. Measurement of LGE in the basal LV may be useful to assess arrhythmia risk in patients with pathogenic
TTN
variants.