Clinical Management Decisions Research Articles

IMG-15. A STRATEGIC FLOWCHART FOR PREOPERATIVE IMAGING IN PEDIATRIC POSTERIOR FOSSA TUMORS

Abstract BACKGROUND This comprehensive study delves into pediatric posterior fossa tumors (PFTs), focusing on both common and rare types, including pseudoneoplasms. The aim is to understand the diagnostic challenges of these less typical tumors, enhancing knowledge beyond usual pathologies. A detailed flow chart has been created to aid in accurate preoperative diagnoses. METHODS The study examines neuroimaging data, primarily from MRI and CT scans, collected from various clinical studies and case reports. It concentrates on identifying unique imaging characteristics of rare PFTs and pseudoneoplasms. The flow chart considers lesion location in various anatomical areas of the posterior fossa and factors such as lesion localization, MRI details (including DWI), and patient age. It also emphasizes the identification of cells in the posterior fossa that can lead to tumors, including osseous tissue cells, dura mater cells, arachnoid cells, pia mater cells, various glial cells, neurons, and choroid plexus cells. RESULTS The study reveals distinct imaging features of less common PFTs and pseudoneoplasms, critical for differentiating them from more common tumors. Advanced imaging techniques are highlighted as essential for improving diagnostic accuracy, impacting clinical management and treatment decisions. The review also discusses the varied presentation of tumors and the challenges this poses to standard diagnostic methods. CONCLUSIONS Understanding the imaging characteristics of rare PFTs and pseudoneoplasms, especially in children, is vital. This thorough analysis enhances diagnostic accuracy and influences treatment approaches, potentially improving patient outcomes. The study underscores the necessity of combining clinical observations with advanced imaging for precise diagnoses in atypical cases. This approach is crucial for healthcare professionals managing pediatric PFTs, leading to better clinical decisions and advancing pediatric neuro-oncology.

NFS-21. DEMOGRAPHIC, CLINICAL AND IMAGING CHARACTERISTICS OF NEWLY DIAGNOSED OPTIC PATHWAY GLIOMAS ASSOCIATED WITH NF1: RESULTS FROM THE INTERNATIONAL MULTICENTER NF1-OPG NATURAL HISTORY STUDY

Abstract BACKGROUND Treatment and clinical management decisions for children with NF1-OPGs remain challenging as most existing data are retrospective and have not included standardized visual outcomes. In this study, we prospectively enrolled newly diagnosed NF1-OPGs and performed standardized neuro-oncology and ophthalmology assessments in order to develop evidence-based guidelines for monitoring and treatment. METHODS Children with NF1-OPG on MRI who were evaluated by both a study ophthalmologist and neuro-oncologist/NF1 expert within 1 month of radiologic diagnosis were eligible for enrollment. All subjects attempted quantitative visual acuity using Teller acuity cards (TAC) as well as ATS-HOTV testing. The neuro-oncologist/NF1 expert provided reasons for obtaining the MRI as well as initiating treatment, if applicable. Descriptive statistics calculated the success rate of acquiring TAC and reasons to obtain the MRI. RESULTS Two-hundred fifty subjects from 22 institutions were enrolled and had at least one visit beyond baseline (Median age 3.1 years, range 0.1–16.8; 53% female). TAC was successfully acquired in both eyes (N=195, 78%) and at least one eye in (N=206, 82%). ATS-HOTV was successfully acquired in both eyes (N=97, 39%) and at least one eye in (N=98, 39%). The two most common reasons to obtain an MRI were screening due to a diagnosis of NF1 (N=99, 39%) and ophthalmologic concern (N=81, 32%). At enrollment, continued observation occurred in a majority of subjects (N=221, 88%) while treatment with chemotherapy was initiated in only 11% (N=29). Twenty-nine (11%) subjects initially observed transitioned to treatment after enrollment (range: 2.5–25 months) thus far. DISCUSSION We present a prospective multicenter study of children with newly diagnosed NF1-OPGs. The ability to acquire quantitative visual acuity was higher than anticipated. The frequency of NF1-OPGs requiring treatment is lower than previously reported. Regression models of clinical and MRI features that prompted immediate treatment with chemotherapy versus observation will be discussed.

Clinicians' experiences and perspectives of a web-based lung cancer referral pathway.

e13539 Background: Efficient and streamlined referral of patients with suspected lung cancer is an integral part of providing optimal care for these patients. There is emerging evidence that use of online care pathways, such as HealthPathways is associated with improved referral quality from primary care, more timely access to secondary care and standardization of clinical management decisions by general practitioners (GPs). The Townsville Lung Cancer Referral Pathway (TLCRP) is part of ' Townsville HealthPathways', which is the evidence-based clinical pathway portal used in the Townsville Hospital and Health service in northern Australia. This study aimed to explore the experiences and perspectives of clinicians about TLCRP. Methods: This was a descriptive qualitative study nested within a larger project evaluating TLCRP, utilising a broader implementation science framework. In-depth, semi-structured interviews of GPs and lung cancer specialists were conducted. An iterative, inductive thematic analysis of interview transcripts was undertaken to derive key codes and themes regarding participant experiences and perceptions. Results: Twenty interviews were conducted, 14 with GPs and six with specialists across disciplines of respiratory medicine, oncology, and cardiothoracic surgery. Of the GPs, 11 were practicing in the regional locality of Townsville and three practiced in surrounding rural areas. Interview analysis identified two major themes and several sub-themes (Table). Several enablers and barriers to implementing TLCRP were identified. Barriers to adaptation of TLCRP included lack of clinical time, resistance to changing referral patterns, lack of familiarity or experience with HealthPathways and technology issues. Enablers included clinical usefulness of TLCRP, support from HealthPathways implementing team, integration of TLCRP with the electronic referral system and positive feedback from specialists. Conclusions: Emerging themes from this study may be used to reduce the barriers and improve uptake of TLCRP and other health care pathways in the local health service. Improving the uptake of TLCRP may mean that more patients in our region experience a streamlined journey to more timely specialist lung cancer care and improved health outcomes. [Table: see text]

Trajectories of chronic multimorbidity patterns in older patients: MTOP study

BackgroundMultimorbidity is associated with negative results and poses difficulties in clinical management. New methodological approaches are emerging based on the hypothesis that chronic conditions are non-randomly associated forming multimorbidity patterns. However, there are few longitudinal studies of these patterns, which could allow for better preventive strategies and healthcare planning. The objective of the MTOP (Multimorbidity Trajectories in Older Patients) study is to identify patterns of chronic multimorbidity in a cohort of older patients and their progression and trajectories in the previous 10 years.MethodsA retrospective, observational study with a cohort of 3988 patients aged > 65 was conducted, including suspected and confirmed COVID-19 patients in the reference area of Parc Taulí University Hospital. Real-world data on socio-demographic and diagnostic variables were retrieved. Multimorbidity patterns of chronic conditions were identified with fuzzy c-means cluster analysis. Trajectories of each patient were established along three time points (baseline, 5 years before, 10 years before). Descriptive statistics were performed together with a stratification by sex and age group.Results3988 patients aged over 65 were included (58.9% females). Patients with ≥ 2 chronic conditions changed from 73.6 to 98.3% in the 10-year range of the study. Six clusters of chronic multimorbidity were identified 10 years before baseline, whereas five clusters were identified at both 5 years before and at baseline. Three clusters were consistently identified in all time points (Metabolic and vascular disease, Musculoskeletal and chronic pain syndrome, Unspecific); three clusters were only present at the earliest time point (Male-predominant diseases, Minor conditions and sensory impairment, Lipid metabolism disorders) and two clusters emerged 5 years before baseline and remained (Heart diseases and Neurocognitive). Sex and age stratification showed different distribution in cluster prevalence and trajectories.ConclusionsIn a cohort of older patients, we were able to identify multimorbidity patterns of chronic conditions and describe their individual trajectories in the previous 10 years. Our results suggest that taking these trajectories into consideration might improve decisions in clinical management and healthcare planning.Trial registration numberNCT05717309.

In Vitro Effects of Fentanyl on Aortic Viscoelasticity in a Rat Model of Melatonin Deficiency.

Melatonin influences arterial biomechanics, and its absence could cause remodeling of the arterial wall, leading to increased stiffness. Direct effects of fentanyl on the aortic wall have also been observed previously. This study aimed to evaluate in vitro the effects of fentanyl on aortic viscoelasticity in a rat model of melatonin deficiency and to test the hypothesis that melatonin deficiency leads to increased arterial wall stiffness. The viscoelasticity was estimated in strip preparations from pinealectomized (pin, melatonin deficiency) and sham-operated (sham, normal melatonin) adult rats using the forced oscillations method. In the untreated aortic wall pin, the viscoelasticity was not significantly altered. However, combined with 10-9 M fentanyl, the pin increased the natural frequency (f0) and modulus of elasticity (E') compared to the sham-operated. Independently, fentanyl treatment decreased f0 and E' compared separately to untreated sham and pin preparations. The effects of fentanyl were neither dose-dependent nor affected by naloxone, suggesting a non-opioid mechanism. Furthermore, an independent effect of naloxone was also detected in the normal rat aortic wall, resulting in reduced E'. Additional studies are needed that may improve the clinical decisions for pain management and anesthesia for certain patients with co-occurring chronic low levels of blood plasma melatonin and some diseases.

Enhanced clinical decisions for management of benign prostatic hyperplasia using patient-reported outcomes: protocol for a prospective observational study

BackgroundLower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) significantly impact quality of life among older men. Despite the prevalent use of the American Urological Association Symptom Index (AUA-SI) for BPH, this measure overlooks key symptoms such as pain and incontinence, underscoring the need for more comprehensive patient-reported outcome (PRO) tools. This study aims to integrate enhanced PROs into routine clinical practice to better capture the spectrum of LUTS, thereby improving clinical outcomes and patient care.MethodsThis prospective observational study will recruit men with LUTS secondary to BPH aged ≥ 50 years from urology clinics. Participants will be stratified into medical and surgical management groups, with PRO assessments scheduled at regular intervals to monitor LUTS and other health outcomes. The study will employ the LURN Symptom Index (SI)-29 alongside the traditional AUA-SI and other non-urologic PROs to evaluate a broad range of symptoms. Data on comorbidities, symptom severity, and treatment efficacy will be collected through a combination of electronic health records and PROs. Analyses will focus on the predictive power of these tools in relation to symptom trajectories and treatment responses. Aims are to: (1) integrate routine clinical tests with PRO assessment to enhance screening, diagnosis, and management of patients with BPH; (2) examine psychometric properties of the LURN SIs, including test-retest reliability and establishment of clinically meaningful differences; and (3) create care-coordination recommendations to facilitate management of persistent symptoms and common comorbidities measured by PROs.DiscussionBy employing comprehensive PRO measures, this study expects to refine symptom assessment and enhance treatment monitoring, potentially leading to improved personalized care strategies. The integration of these tools into clinical settings could revolutionize the management of LUTS/BPH by providing more nuanced insights into patient experiences and outcomes. The findings could have significant implications for clinical practices, potentially leading to updates in clinical guidelines and better health management strategies for men with LUTS/BPH.Trial registrationThis study is registered in ClinicalTrials.gov (NCT05898932).

Trigeminal Neuroma: A Case Report and Review of the Literature

Trigeminal neuromas are rare tumors arising from the trigeminal nerve, often presenting diagnostic challenges due to their infrequent occurrence and varied clinical manifestations. We present a case report of 52 year-old female patient presenting with right diplopia and progressive facial pain resistant to standard treatment. Early recognition and appropriate management are crucial to prevent complications and improve patient outcomes. This report underscores the importance of considering trigeminal neuromas in the differential diagnosis of facial pain and the pivotal role of imaging modalities in guiding clinical management decisions.

Clinical management of typical and atypical carcinoids/neuroendocrine tumors in ENETS centres of excellence (CoE): Survey from the ENETS lung NET task force.

Lung carcinoid tumours are neuroendocrine neoplasms originating from the bronchopulmonary tract's neuroendocrine cells, accounting for only 1%-3% of all lung cancers but 30% of all neuroendocrine tumours. The incidence of lung carcinoids, both typical and atypical, has been increasing over the years due to improved diagnostic methods and increased awareness among clinicians and pathologists. The most recent WHO classification includes a subgroup of lung carcinoids with atypical morphology and higher mitotic count and/or Ki67 labelling index. Despite appropriate surgery, the 5-year survival rate for atypical carcinoids barely exceeds 50%-70%. The role of adjuvant therapy in lung carcinoids is not well-defined, and clinical decisions are generally based on the presence of high-risk features. Long-term follow-up is essential to monitor for recurrence, although the optimal follow-up protocol remains unclear. To address the lack of consensus in clinical management decisions, the European Neuroendocrine Tumor Society (ENETS) initiated a survey among 20 expert centres. The survey identified varied opinions on approaches to imaging, surgery, use of adjuvant therapy, and follow-up protocols. Notably, the absence of dedicated multidisciplinary lung neuroendocrine tumour boards in some centres was evident. Experts agreed on the need for a prospective adjuvant trial in high-risk patients, emphasizing the feasibility of such a study. In conclusion, the study highlights the need for a more uniform adoption of existing guidelines in the management of lung carcinoid tumours and emphasizes the importance of international collaboration to advance research and patient care. Close collaboration between healthcare providers and patients is vital for effective long-term surveillance and management of these rare tumours.

Project SATURN– a real-world evidence data collaboration with existing European datasets in Osteogenesis Imperfecta to support future therapies

Regulatory marketing authorisation is not enough to ensure patient access to new medicinal products. Health Technology Assessment bodies may require data on effectiveness, relative effectiveness, and cost-effectiveness. Healthcare systems may require data on clinical utility, savings, and budget impact. Furthermore, the exact requirements of these bodies vary country by country and sometimes even region to region, resulting in a patchwork of different data requirements to achieve effective, reimbursed patient access to new therapies. In addition, clinicians require data to make informed clinical management decisions. This requirement is of key importance in rare diseases where there is often limited data and clinical experience at the time of regulatory approval.This paper describes an innovative initiative that is called Project SATURN: Systematic Accumulation of Treatment practices and Utilization, Real world evidence, and Natural history data for the rare disease Osteogenesis Imperfecta. The objective of this project is to generate a common core dataset by utilising existing data sources to meet the needs of the various stakeholders and avoiding fragmentation through multiple approaches (e.g., a series of individual national requests/approaches, and unconnected with the regulators’ potential requirements). It is expected that such an approach will reduce the time for patient access to life-changing medications. Whilst Project SATURN applies to Osteogenesis Imperfecta, it is anticipated that the principles could also be applied to other rare diseases and reduce the time for patient access to new medications.

Abstract PO3-08-01: Decision curve analysis to compare breast cancer risk predictions for a polygenic integrated clinical risk model with those of a gold standard

Abstract Risk-based guidelines have been developed to provide advice on options that are available to women who are at increased risk of breast cancer. We and others are focused on improving risk prediction models for general population use. For breast cancer, polygenic risk has been identified as important for risk prediction, especially when combined with clinical risk factors such as family history, anthropometric measures, breast imaging measures, and hormonal and reproductive risk factors. When comparing the performance of risk prediction models, the AUC is most often used but it focuses on performance in terms of distinguishing between affected and unaffected individuals and does not take into account differences in the specificity (true negative rate) and sensitivity (true positive rate) of the models being compared. In contrast, decision curve analysis takes sensitivity and specificity into account and enables the comparison of the net benefit of risk prediction tools at the clinical risk thresholds that are used to guide clinical management decisions. Herein, we use decision curve analysis to compare breast cancer risk prediction guidelines for BRISK and the Breast Cancer Risk Assessment Tool (BCRAT) in the UK Biobank, and for BRISK and IBIS version 7 in the Nurses’ Health Study. We evaluated the net benefit at the 5-year risk thresholds (1.67% and 3%) that are used to guide clinical management decisions around risk-reducing medication and at the remaining lifetime risk of 20% that is used to guide supplemental MRI surveillance. In the UK Biobank, BRISK showed a net benefit over BCRAT at the 5-year risk thresholds of 1.67% and 3.0%. The AUCs were 0.649 (95% CI = 0.640, 0.695) for BRISK and 0.567 (95% CI = 0.556, 0.577) for BCRAT and showed that, overall, BRISK discriminated between affected and unaffected women better than BCRAT (P < 0.001). In the Nurses’ Health Study, BRISK showed a net benefit over IBIS at the remaining lifetime risk threshold of 20%. The AUCs were 0.647; 95% CI = 0.627, 0.668 for BRISK and 0.571; 95% CI = 0.546, 0.595 for IBIS, a statistically significant improvement for BRISK over IBIS (P < 0.0001). We also looked at sensitivity, specificity, positive predictive value and negative predictive value even though these risk models are one-step removed from breast cancer diagnosis by screening/risk-reduction options. The positive predictive values are higher for the BRISK (27.1%) model compared to BCRAT (5.5%) in the UK Biobank dataset and higher for BRISK (15.4%) compared to IBISv7 (14.0%) in the Nurses’ dataset. We have shown the application of a statistical tool that can be used to directly compare risk models at clinically relevant thresholds. We have shown that BRISK, which comprises polygenic risk and clinical risk factors, shows higher net benefit at both 1.67% and 3% thresholds compared to BCRAT and at 20% remaining lifetime risk for IBIS version 7. In breast cancer risk prediction, a tool with high specificity (and therefore a necessary trade-off for low sensitivity) is preferred because we do not want to incorrectly classify women as not being at high risk and deny them the opportunity for intervention in the form of more frequent screening, alternative modes of screening or risk-reducing medication. This improvement in general population risk stratification that BRISK can provide has the potential to have a clinically significant effect on women’s health. Citation Format: Erika Spaeth, Bernard A Rosner, Gill Dite. Decision curve analysis to compare breast cancer risk predictions for a polygenic integrated clinical risk model with those of a gold standard [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-08-01.

Large submucous uterine fibroid mass

Background: Uterine fibroids or leiomyomas, are common benign tumors originating from the smooth muscle cells of the uterus. While typically asymptomatic, large submucous fibroids can cause significant clinical manifestations, including abnormal uterine bleeding, pelvic pain, and reproductive issues. Radiological imaging, such as ultrasound, played a crucial role in the accurate diagnosis and characterization of these fibroids, guiding appropriate clinical management decisions. Methods: We present a case report of a 28-year-old female with complaints of heavy menstrual bleeding and pelvic discomfort. Clinical evaluation prompted the utilization of radiological imaging techniques to assess the uterine anatomy. Ultrasound was employed to visualize and characterize the large submucous uterine fibroid mass. Imaging findings were correlated with clinical symptoms to formulate an appropriate treatment plan. Results: ultrasound revealed a large submucous uterine fibroid mass measuring 105.7mm x 75.6mm x 79.6mm in its dimensions. The fibroid was heterogeneous in its echo texture and it is located in the submucosal layer of the uterus. Doppler imaging demonstrated some areas of flow within the fibroid mass. The correlation of imaging findings with clinical symptoms aided in determining the extent of fibroid-related symptoms and guiding further management decisions. Conclusion: This case report underscores the significance of radiological imaging, particularly ultrasound in diagnosing and characterizing large submucous uterine fibroid masses. Accurate radiological assessment is crucial for determining the appropriate course of clinical management, which may include medical therapy, minimally invasive procedures, or surgical intervention. The collaborative approach between gynecologists and radiologists is pivotal in optimizing patient care for individuals with symptomatic uterine fibroids.

Clinical prediction models for treatment outcomes in newly diagnosed epilepsy: A systematic review.

Up to 35% of individuals diagnosed with epilepsy continue to have seizures despite treatment, commonly referred to as drug-resistant epilepsy. Uncontrolled seizures can directly, or indirectly, negatively impact an individual's quality of life. To inform clinical management and life decisions, it is important to be able to predict the likelihood of seizure control. Those likely to achieve seizure control will be able to return sooner to their usual work and leisure activities and require less follow-up, whereas those with a poor prognosis will need more frequent clinical attendance and earlier consideration of epilepsy surgery. This is a systematic review aimed at identifying demographic, clinical, physiological (e.g., electroencephalographic), and imaging (e.g., magnetic resonance imaging) factors that may be predictive of treatment outcomes in patients with newly diagnosed epilepsy (NDE). MEDLINE and Embase were searched for prediction models of treatment outcomes in patients with NDE. Study characteristics were extracted and subjected to assessment of risk of bias (and applicability concerns) using the PROBAST (Prediction Model Risk of Bias Assessment Tool) tool. Baseline variables associated with treatment outcomes are reported as prognostic factors. After screening, 48 models were identified in 32 studies, which generally scored low for concerns of applicability, but universally scored high for susceptibility to bias. Outcomes reported fit broadly into four categories: drug resistance, short-term treatment response, seizure remission, and mortality. Prognostic factors were also heterogenous, but the predictors that were commonly significantly associated with outcomes were those related to seizure characteristics/types, epilepsy history, and age at onset. Antiseizure medication response was often included as a baseline variable, potentially obscuring other factor relationships at baseline. Currently, outcome prediction models for NDE demonstrate a high risk of bias. Model development could be improved with a stronger adherence to recommended TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) practices. Furthermore, we outline actionable changes to common practices that are intended to improve the overall quality of prediction model development in NDE.

Genetic and phenotypic analysis of 225 Chinese children with developmental delay and/or intellectual disability using whole-exome sequencing

Developmental delay (DD), or intellectual disability (ID) is a very large group of early onset disorders that affects 1–2% of children worldwide, which have diverse genetic causes that should be identified. Genetic studies can elucidate the pathogenesis underlying DD/ID. In this study, whole-exome sequencing (WES) was performed on 225 Chinese DD/ID children (208 cases were sequenced as proband-parent trio) who were classified into seven phenotype subgroups. The phenotype and genomic data of patients with DD/ID were further retrospectively analyzed. There were 96/225 (42.67%; 95% confidence interval [CI] 36.15–49.18%) patients were found to have causative single nucleotide variants (SNVs) and small insertions/deletions (Indels) associated with DD/ID based on WES data. The diagnostic yields among the seven subgroups ranged from 31.25 to 71.43%. Three specific clinical features, hearing loss, visual loss, and facial dysmorphism, can significantly increase the diagnostic yield of WES in patients with DD/ID (P = 0.005, P = 0.005, and P = 0.039, respectively). Of note, hearing loss (odds ratio [OR] = 1.86%; 95% CI = 1.00-3.46, P = 0.046) or abnormal brainstem auditory evoked potential (BAEP) (OR = 1.91, 95% CI = 1.02–3.50, P = 0.042) was independently associated with causative genetic variants in DD/ID children. Our findings enrich the variation spectrums of SNVs/Indels associated with DD/ID, highlight the value genetic testing for DD/ID children, stress the importance of BAEP screen in DD/ID children, and help to facilitate early diagnose, clinical management and reproductive decisions, improve therapeutic response to medical treatment.

Use of a SimBox, a Video-Augmented, Newborn Resuscitation Simulation for Prehospital Providers to Measure Clinical Performance and Educational Experience.

Few studies have described the current clinical practices, adherence to guidelines, and outcomes of newborn resuscitations attended by emergency medical services (EMS). SimBox, a novel, video-augmented simulation, was used to describe the adherence of prehospital providers to Neonatal Resuscitation Program guidelines, to measure satisfaction with the simulation intervention, and to describe the self-reported improvement in knowledge, skills, and attitudes after the simulation. A prospective observational cohort study of EMS providers was designed and conducted using SimBox, an open-access simulation platform, and facilitated by EMS educators. Clinical performance measures were collected using a five-item checklist. Simulation satisfaction measures were collected through net promoter scores. Learners' demographics, and self-reported knowledge, skills, and attitudes were measured using a retrospective survey of 25 questions. In total, 33 facilitator and 55 learner surveys were collected across Connecticut, Colorado, and Alaska between July 2021 and September 2022. At least one deviation from clinical guidelines occurred in 22/30 (73.3%) of the sessions, with 10/30 (33.3%) teams inappropriately performing chest compressions, 5/31 (16.1%) teams not warming, drying, stimulating, and suctioning the newborn, and 7/31 (22.6%) teams not performing positive pressure ventilation correctly. Lastly, 10/30 (33.3%) teams administered an incorrect dose of dextrose-containing fluids. Very high levels of satisfaction were reported with net promoter scores of 97 and 82 out of 100 for the facilitator and learner surveys, respectively. Finally, all 55/55 (100%) of the learners strongly or somewhat agreed that the simulation improved their knowledge, teamwork, communication, and psychomotor skills. In this cohort of prehospital providers, clinical management decisions during a newborn resuscitation simulation often deviated from the gold-standard, newborn resuscitation guidelines. Free, online, open-access simulation resources like SimBox can be used to identify and measure practice deviations from standardized resuscitation protocols in the prehospital setting.

Conventional Cytogenetic Analysis and Array CGH + SNP Identify Essential Thrombocythemia and Prefibrotic Primary Myelofibrosis Patients Who Are at Risk for Disease Progression.

The Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-MPNs) are a heterogeneous group of clonal hematopoietic malignancies that include polycythemia vera (PV), essential thrombocythemia (ET), and the prefibrotic form of primary myelofibrosis (prePMF). In this study, we retrospectively reviewed the karyotypes from conventional cytogenetics (CC) and array Comparative Genomic Hybridization + Single Nucleotide Polymorphism (aCGH + SNP) in patients with ET or prePMF to determine whether the combined analysis of both methodologies can identify patients who may be at a higher risk of disease progression. We performed a comprehensive genomic review on 169 patients with a clinical diagnosis of ET (154 patients) or prePMF (15 patients). Genomic alterations detected by CC or array-CGH + SNP were detected in 36% of patients. In patients who progressed, 68% had an abnormal genomic finding by either technology. There was a shorter progression-free survival (PFS) among patients who were cytogenetically abnormal or who were cytogenetically normal but had an abnormal aCGH + SNP result. Leveraging the ability to detect submicroscopic copy number alterations and regions of copy neutral-loss of heterozygosity, we identified a higher number of patients harboring genomic abnormalities than previously reported. These results underscore the importance of genomic analysis in prognostication and provide valuable information for clinical management and treatment decisions.

Secondary School Athletic Trainers' Perceptions of the Influence of Social Determinants of Health and Socioeconomic Status on Clinical Management Decisions.

Evidence suggests that lower socioeconomic status (SES) and negative social determinants of health (SDOH) contribute to health care disparities. Due to their accessibility in the high school setting, secondary school athletic trainers (SSATs) may encounter patients who are historically underserved in health care, such as patients with low SES. However, a significant gap in knowledge exists regarding how SDOH and SES may influence SSATs' clinical management decisions. To describe SSATs' perceptions of how patient SDOH and SES influence clinical management decisions and to identify barriers to athletic health care. Cross-sectional study. Online survey. National Athletic Trainers' Association SSATs (6.7% response rate). Secondary school athletic trainers were asked about their perceptions of patient SDOH and SES (content validity index = 0.83 for relevancy). The levels of relevance and agreement were answered on a 4-point Likert scale. Data were summarized using means and SDs, frequencies and proportions (%), and median scores. A total of 380 SSATs participated (mean years of experience = 14.9 ± 11.7 years). When providing care, most (71.3%) SSATs believed their patients' health or health care access to be the most relevant of the 5 SDOH, whereas the other 4 SDOH were less than 60% relevant. Most SSATs agreed or strongly agreed that patient SES affected both referral (67.4%) and the reliance on conservative treatment before referral (71.2%). Secondary school athletic trainers identified patient or guardian compliance (70.2%) and type of health insurance (61.5%) as barriers to providing care to patients with low SES. Secondary school athletic trainers perceived health or health care access as the most relevant social determinant when providing care to patients with low SES. When SSATs further considered the SES of patients, they identified all SDOH as barriers that they were ill equipped to navigate as they delivered care and engaged in patient referral.

Clinical decisions for appropriate management of patients with atrial fibrillation.

The management of patients with atrial fibrillation (AF) requires intricate clinical decision-making to optimize outcomes. In everyday clinical practice, physicians undergo difficult choices to better manage patients with AF. They need to balance thromboembolic and bleeding risk to focus on patients' symptoms and to manage a variety of multiple comorbidities. In this review, we aimed to explore the multifaceted dimensions of clinical decision-making in AF patients, encompassing the definition and diagnosis of clinical AF, stroke risk stratification, oral anticoagulant therapy selection, consideration of bleeding risk, and the ongoing debate between rhythm and rate control strategies. We will also focus on possible grey zones for the management of AF patients. In navigating this intricate landscape, clinicians must reconcile the dynamic interplay of patient-specific factors, evolving guidelines, and emerging therapies. The review underscores the need for personalized, evidence-based clinical decision-making to tailor interventions for optimal outcomes according to specific AF patient profiles.

Abstract 2806: A single dose of perioperative cefazolin disrupts the gut microbiome and immunity in patients (pts) with early-stage melanoma

Abstract Background: Perioperative antibiotic prophylaxis is routinely utilized to reduce surgical site infections (SSIs). However, the rate of SSIs following a clean surgical procedure is <3%. Overuse of antibiotics is associated with potential adverse effects, including disruption of the composition and function of the native gut microbiota. Numerous studies have shown a negative impact of antibiotics on response and survival in patients with cancer treated with immune checkpoint blockade. The primary objective of this study was to determine the impact of a single dose of perioperative cefazolin on the gut microbiome and immunity. Methods: In this pilot trial (NCT04875728), 22 eligible pts diagnosed with clinical stage I or II melanoma undergoing wide excision with or without sentinel lymph node biopsy were enrolled between October 2021 and January 2023. Pts were randomized 1:1 to receive a single dose of cefazolin as standard-of-care (ABX, n=11) or no antibiotics (No ABX, n=11) at the time of surgery. Stool samples were collected before surgery, on post-operative day (POD) 14 and POD90 for metagenomic sequencing (WMS). Bulk RNA-sequencing of peripheral blood mononuclear cells (PBMCs) collected at the same timepoints was performed and data processed using DESeq2, log-transformed, and standardized for subsequent analysis. Immune pathway enrichment scores were calculated using GSVA for each sample with gene lists from 3 immune pathways (ADAPTIVE_IMMUNE_SYSTEM, INNATE_IMMUNE_SYSTEM, and CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM) from REACTOME (https://reactome.org) and immune cell gene signatures from Danaher P et al, 2017. Results: Treatment with a single dose of perioperative cefazolin was associated with a decrease in the alpha diversity of the gut microbiome 2 weeks postoperatively in pts who received perioperative cefazolin versus those who did not receive antibiotics (p=0.057, R2=0.0526); this persisted to POD90 (p=0.021, R2=0.0948). WMS showed prominent and persistent decreases in Akkermansia muciniphila (POD14: Log2FC=-8.38, q<0.001) and Alistipes communis (POD90: Log2FC=-4.47, q<0.001) in the ABX group compared to No ABX, respectively. RNA-seq analysis of PBMCs from pts revealed differences in immune subsets at POD90 between ABX and No ABX groups including decreased IFN-γ signatures (p=0.02) in pts who received perioperative cefazolin. Conclusions: Perioperative antibiotic prophylaxis is associated with profound and persistent reduction in microbiome diversity and composition, particularly of bacterial species associated with protective metabolic and inflammatory effects. Further studies will seek to assess the functional impact of this reduction on the immune response in a murine model, evaluate the generalizability of our findings across broader cohorts of patients undergoing surgery, and apply these findings to guide clinical management decisions. Citation Format: Estefania Fernandez, Samuel Cass, Yongwoo D. Seo, Ashish V. Damania, Xiaolong Meng, Pranoti V. Sahasrabhojane, Jiun Sheng Liu, Wenbin Liu, Yulong Chen, Roland L. Bassett, Samuel Shelburne, Hsiu-Yin Chang, Kinjal R. Somaiya, Kristi S. Mungovan, Jared C. Malke, Brenna Matejka, Sarah B. Fisher, Anthony Lucci, Jeffrey E. Lee, Merrick I. Ross, Jeffrey E. Gershenwald, Padmanee Sharma, Nadim J. Ajami, Christina L. Roland, Jennifer A. Wargo, Emily Z. Keung. A single dose of perioperative cefazolin disrupts the gut microbiome and immunity in patients (pts) with early-stage melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2806.

A prognostic signature of fatty acid metabolism-related genes for predicting survival of gastric cancer patients.

To analyze the expression profile of fatty acid metabolism (FAM)-related genes, identify a prognostic signature, and evaluate its clinical value for gastric cancer (GC) patients. The mRNA expression profiles of 493 FAM-related genes were obtained from TCGA database. Differentially expressed genes (DEGs) between cancer and non-cancer samples were identified, and their relationships with overall survival (OS) of GC patients were evaluated. A prognostic signature of FAM-related genes was identified by the LASSO regression model, and its predictive performance was tested by an independent external cohort. Ninety-three DEGs were identified, of which 44 were downregulated and 49 were upregulated. After optimizing risk characteristics, a prognostic signature of four FAM-related genes (ACBD5, AVPR1A, ELOVL4, and FAAH) were developed. All patients were divided into high-risk (>1.020) and low-risk groups (≤1.020) on the basis of the median risk score. Survival analysis indicated that high-risk patients had a shorter OS than low-risk patients (5-year OS rate, 26.3% vs. 45.0%, p < 0.001). The AUC values for the prediction of 3-year and 5-year OS were 0.664 and 0.624, respectively. In the GSE62254 data set, the 5-year OS rate of high-risk and low-risk patients were 44.7% versus 61.5%, respectively (p = 0.003). The AUC values were 0.632 and 0.627 at 3-year and 5-year prediction. The prognostic signature of FAM-related genes was an independent predictor of OS (hanzard ratio [HR] for TCGA cohort: 1.851, 95% confidence interval [CI]: 1.394-2.458, p < 0.001; HR for GSE62254: 1.549, 95% CI: 1.098-2.185, p = 0.013). The risk signature of four FAM-related genes was a valuable prognostic tool, and it might be helpful for clinical management and therapeutic decision of gastric cancer patients.

Risk of cardiovascular death in patients with hepatocellular carcinoma based on the Fine-Gray model.

Hepatocellular carcinoma (HCC) is one of the most common types of cancers worldwide, ranking fifth among men and seventh among women, resulting in more than 7 million deaths annually. With the development of medical technology, the 5-year survival rate of HCC patients can be increased to 70%. However, HCC patients are often at increased risk of cardiovascular disease (CVD) death due to exposure to potentially cardiotoxic treatments compared with non-HCC patients. Moreover, CVD and cancer have become major disease burdens worldwide. Thus, further research is needed to lessen the risk of CVD death in HCC patient survivors. To determine the independent risk factors for CVD death in HCC patients and predict cardiovascular mortality (CVM) in HCC patients. This study was conducted on the basis of the Surveillance, Epidemiology, and End Results database and included HCC patients with a diagnosis period from 2010 to 2015. The independent risk factors were identified using the Fine-Gray model. A nomograph was constructed to predict the CVM in HCC patients. The nomograph performance was measured using Harrell's concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and area under the ROC curve (AUC) value. Moreover, the net benefit was estimated via decision curve analysis (DCA). The study included 21545 HCC patients, of whom 619 died of CVD. Age (< 60) [1.981 (1.573-2.496), P < 0.001], marital status (married) [unmarried: 1.370 (1.076-1.745), P = 0.011], alpha fetoprotein (normal) [0.778 (0.640-0.946), P = 0.012], tumor size (≤ 2 cm) [(2, 5] cm: 1.420 (1.060-1.903), P = 0.019; > 5 cm: 2.090 (1.543-2.830), P < 0.001], surgery (no) [0.376 (0.297-0.476), P < 0.001], and chemotherapy(none/unknown) [0.578 (0.472-0.709), P < 0.001] were independent risk factors for CVD death in HCC patients. The discrimination and calibration of the nomograph were better. The C-index values for the training and validation sets were 0.736 and 0.665, respectively. The AUC values of the ROC curves at 2, 4, and 6 years were 0.702, 0.725, 0.740 in the training set and 0.697, 0.710, 0.744 in the validation set, respectively. The calibration curves showed that the predicted probabilities of the CVM prediction model in the training set vs the validation set were largely consistent with the actual probabilities. DCA demonstrated that the prediction model has a high net benefit. Risk factors for CVD death in HCC patients were investigated for the first time. The nomograph served as an important reference tool for relevant clinical management decisions.