Citations

Abstract Objective The American Medical Informatics Association (AMIA) Task Force on Diversity, Equity, and Inclusion (DEI) was established to address systemic racism and health disparities in biomedical and health informatics, aligning with AMIA’s mission to transform healthcare. AMIA’s DEI initiatives were spurred by member voices responding to police brutality and COVID-19’s impact on Black/African American communities. Materials and Methods The Task Force, consisting of 20 members across 3 groups aligned with AMIA’s 2020-2025 Strategic Plan, met biweekly to develop DEI recommendations with the help of 16 additional volunteers. These recommendations were reviewed, prioritized, and presented to the AMIA Board of Directors for approval. Results In 9 months, the Task Force (1) created a logic model to support workforce diversity and raise AMIA’s DEI awareness, (2) conducted an environmental scan of other associations’ DEI activities, (3) developed a DEI framework for AMIA meetings, (4) gathered member feedback, (5) cultivated DEI educational resources, (6) created a Board nominations and diversity session, (7) reviewed the Board’s Strategic Planning for DEI alignment, (8) led a program to increase diversity at the 2020 AMIA Virtual Annual Symposium, and (9) standardized socially-assigned race and ethnicity data collection. Discussion The Task Force proposed actionable recommendations that focused on AMIA’s role in addressing systemic racism and health equity, helping the organization understand its member diversity. Conclusion This work supported marginalized groups, broadened the research agenda, and positioned AMIA as a DEI leader while reinforcing the need for ongoing transformation within informatics.

Abstract Many patients in the emergency department present with signs and symptoms that arouse concern for sepsis; however, other explanations are also possible. There are currently no rapid tests used in clinical practice that reliably distinguish the presence of a bacterial or viral infection vs. a non-infectious etiology and can predict a patient’s likelihood to decompensate. The diagnostic and prognostic uncertainty in “gray zone” patients complicates the decision to begin therapy as clinicians need to balance the risk of withholding therapy vs. the risk of the therapy itself (e.g., overtreatment with antibiotics and hospitalization, which is costly, potentially harmful, and contributes to antibiotic resistance). The TriVerity™ Test uses isothermal amplification and machine-learning algorithms to quantify and interpret mRNA expression levels to determine both likelihood of bacterial infection, viral infection, or no infection, and whether the patient will likely require one or more critical interventions within 7 days. The three scores each fall into one of five interpretation bands ranging from Very high to Very low. Testing takes approximately 30 minutes using the proprietary Myrna™ Instrument with an operator hands-on-time of under one minute. We enrolled 1,222 patients from 22 emergency departments (ED) to validate the performance of the TriVerity Test. Patients were treated as per local standard of care and were followed for 28 days. Bacterial and viral TriVerity results were validated against clinically adjudicated infection status; the illness severity TriVerity result was validated against the need for at least one critical interventions within 7 days. The bacterial TriVerity result had high AUROC for the diagnosis of bacterial infection (0.83; 80% CI 0.81–0.85) and divided bacterial infection likelihood scores into five interpretation bands with increasing likelihood ratios of infection ranging from Very low (LR- 0.08, 80% CI 0.06–0.11) to Very high (LR + 8.04, 80% CI 5.72–11.78). The AUROC for the bacterial TriVerity result was significantly higher compared to AUROCs for C-reactive protein, procalcitonin or white blood cell count. Similarly, the viral TriVerity score showed high AUROC for the diagnosis of viral infection (0.91; 80% CI 0.90–0.93) and likelihood ratios from Very low (LR- 0.09, 80% CI 0.05–0.14) to Very high (LR + 40.93; 80% CI 29.11–79.23). The TriVerity Illness Severity score showed a high AUROC for the prediction of illness severity (0.77; 80% CI 0.77–0.81) with scores divided into five interpretation bands with increasing likelihood ratios ranging from Very low (LR- 0.22; 80% CI 0.14–0.33) to Very high (LR + 11.33; 80% CI 7.31–17.00). TriVerity illness severity results allowed marked re-classification of the risk for “ICU-level care” as compared to clinical assessment (qSOFA scores) alone. In conclusion, TriVerity provides rapid, highly accurate and actionable results for the diagnosis and prognosis of patients with suspected acute infection and/or sepsis, supporting a major unmet medical need. TriVerity may improve personalized management of patients with suspected acute infections and suspected sepsis for improved overall healthcare outcomes.

Abstract The grey matter of the brain develops and declines in coordinated patterns during the lifespan. Such covariation patterns of grey matter structure can be quantified as grey matter networks, which can be measured with magnetic resonance imaging. In Alzheimer’s disease, the global organization of grey matter networks becomes more random, which is captured by a decline in the small-world coefficient. Such decline in the small-world value has been robustly associated with cognitive decline across clinical stages of Alzheimer’s disease. The biological mechanisms causing this decline in small-world values remain unknown. Cerebrospinal fluid (CSF) protein biomarkers are available for studying diverse pathological mechanisms in humans and can provide insight into decline. We investigated the relationships between 10 CSF proteins and small-world coefficient in mutation carriers (N = 219) and non-carriers (N = 136) of the Dominantly Inherited Alzheimer Network Observational study. Abnormalities in Amyloid beta, Tau, synaptic (Synaptosome associated protein-25, Neurogranin) and neuronal calcium-sensor protein (Visinin-like protein-1) preceded loss of small-world coefficient by several years, while increased levels in CSF markers for inflammation (Chitinase-3-like protein 1) and axonal injury (Neurofilament light) co-occurred with decreasing small-world values. This suggests that axonal loss and inflammation play a role in structural grey matter network changes.

Stenosis of the left main coronary artery (LM stenosis) is associated with significant mortality and morbidity due to the large area of affected myocardium. Evidence on the use of percutaneous coronary intervention (PCI) for the treatment of LM stenosis is growing. However, the role of Western guidelines on patients in the Asian-Pacific region is unclear due to anatomical variations, substantial heterogeneity in healthcare resources and infrastructure, and the lack of consensus on the optimal management of LM stenosis in the Asia-Pacific region. Hence, an Asian Pacific Society of Cardiology (APSC) working group developed consensus recommendations on the use of PCI in the management of LM stenosis in the Asia-Pacific region. The APSC expert panel reviewed and appraised the available evidence using the Grading of Recommendations Assessment, Development, and Evaluation system. Consensus recommendations were developed and put to an online vote. Consensus was reached when 80% of votes for a given recommendation were in support of ‘agree’ or ‘neutral’. The resulting 12 statements provide guidance for clinical practitioners in the region on the use of PCI in the treatment of patients with LM stenosis.

Abstract Objective The presence of comorbidities can substantially affect patients’ quality of life, but data regarding their impact on idiopathic inflammatory myopathies (IIMs) are limited. Methods We examined the prevalence of comorbidities in IIM patients, other autoimmune rheumatic diseases (oAIRDs) and healthy controls (HCs), using data from the self-reported COVAD-2 survey. We defined basic multimorbidity (BM) as the presence of ≥2 non-rheumatic chronic conditions and complex multimorbidity (CM) as the presence of ≥3 non-rheumatic chronic conditions affecting ≥3 organ systems. Hierarchical clustering on principal components was performed for grouping. Results Among the COVAD respondents, 1558 IIMs, 4591 oAIRDs and 3652 HCs were analysed. IIMs exhibited a high burden of comorbidities (odds ratio [OR]: 1.62 vs oAIRDs and 2.95 vs HCs, P < 0.01), BM (OR: 1.66 vs oAIRDs and 3.52 vs HCs, P < 0.01), CM (OR: 1.69 vs AIRDs and 6.23 vs HCs, P < 0.01) and mental health disorders (MHDs) (OR: 1.33 vs oAIRDs and 2.63 vs HCs, P < 0.01). Among the IIM patients, those with comorbidities or MHDs had lower PROMIS Global Physical (PGP), PROMIS Global Mental (PGM), and PROMIS Physical Function (SF10) scores, and higher fatigue (F4a) scores (all P < 0.001). PGP, PGM, SF10a and F4a were influenced by age, active disease, BM and MHDs. Four distinct clusters were identified among the IIMs according to comorbidities and PROMIS scores. Conclusion Patients with IIMs have a higher burden of comorbidities that influence physical and mental health, identifiable as clinical clusters for optimized and holistic management approaches.

Abstract Intro: Compared to white men, Black men bear the highest burden of prostate cancer, experiencing a higher incidence and mortality rate, and poorer survivorship outcomes. Although prioritized, survivorship and quality of life (QOL) are under-studied in the fight against prostate cancer disparities. To address this issue, clinicians, researchers, and community advocates have formed the Inclusive Cancer Care Research Equity (iCCaRE) Consortium for Black Men. iCCaRE’s goal is to advance the science and practice of survivorship focused on the needs of Black men and their loved ones affected by prostate cancer. Methods: We developed a survivorship care plan (SCP) tailored to the whole person's needs. IRB-approved qualitative methods to preliminarily gain evaluation and guidance on the SCP. The SCP presented content in the following areas: diagnosis and treatment, follow-up care/surveillance, family history, care team, major co-morbidities, symptoms and quality of life, survivorship concerns, and health advisories. Results: 23 Black prostate cancer survivors (PCS) participated and provided feedback on the SCP Mean age was 64 years. PCS diagnosed between 2018-2023 between stages 1-4. The Majority of PCS were provided information for follow-up and side effects. But none had received a comprehensive SCP All agreed that the SCP would contribute to enhancing cancer knowledge, patient activation, and shared decision, and their QOL, if the SCP was obtained. A survivor noted “having inspirational quotes throughout the SCP is important”. An unforeseen consequence to the interviews was the emotional release for the men, justifying the need for the SCP and an expansion of its scope. Domains that the men wanted more contents were social support, sexuality, masculinity, and maintaining a healthy lifestyle. All PCS understood the value of having trusted family and friends to bear the burden of the disease despite some not having a solid support system. PCS emphasized the role of family support stating, “my wife and children helped me stay positive”. Another critical lifestyle component that survivors mentioned was their sexuality and how it directly reflects their masculinity. Although PCS adapted to other forms of intimacy like couples’ activities and stronger communication with their partners, majority of men struggle with adapting to their sexual performance. A quote by a survivor encompasses the mindset expressed by many of the men fear “Like a track star in his prime who can’t run anymore”. Erectile Dysfunction can lead to fear and anxiety among survivors, ultimately affecting QOL. Lastly, PCS wanted more options to stay fit and healthy. Further research and resources are needed to address survivor concerns in this area. Discussion: Overall, PCS have acknowledged that the SCP can assist them in these areas of concern, but more research is required. Life after prostate cancer treatment is an ongoing process; while some survivors cope better than others, it is evident a need for more information and guidance is not being provided to all those affected. Citation Format: James Morrison, Kimlin Ashing, Gaole Song, John McCall, Timethia J. Bonner, Che Ngufor, Getachew A. Dagne, Arnold Merriweather, Ewan Cobran, Cassandra N. Moore, Fornati Bedell, Rotimi Oladapo, Floyd B. Willis, JoAnne S. Oliver, Ernie Kaninjing, Roxana Dronca, Folakemi T. Odedina. iCCaRE qualitative interviews for Black prostate cancer survivors and quality of life [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C042.

Background Although flow diverters (FDs) have benefited from several technical improvements, recently concerns have arisen regarding the braid stability after implantation. Thus, we investigated frequency, predictive factors, and clinical impact of the phenomenon of FD braid deformation (FDBD). Methods Consecutive intracranial aneurysms (IAs) treated with various FDs, between January 2018 and July 2023, were reviewed to identify FDBD (defined as the deformation of a FD without any external force applied to it). Patient, aneurysm, procedural, and FD characteristics were retrieved and analyzed using univariate and multivariable analyses. Morbidity is defined as a score of +1 in the modified Rankin Scale at 3 months. Results In total, 245 FD procedures (271 FDs implanted; 25 multiple IAs treated with 1 FD) in 228 patients; FDBD was observed in 36/245 cases (14.7%), mainly at follow-up angiography (32/36, 88.9%); fish-mouthing was the most frequent FDBD. Morbidity was related to fish-mouthing and braid collapse and was significantly higher in the FDBD group after retreatment (p=0.04). Drawn filled tubing with platinum (DFT) (adjusted odds ratio (aOR)=7.0, 95% CI 3.0 to 17.5; p<0.001) and FD diameter (aOR=2.2, 95% CI 1.3 to 4.1; p<0.01) were identified as independent predictors of FDBD. The metal alloy composing the FD (p=0.13) and coated surfaces were not significantly associated with FDBD (p=0.54 in multivariable analysis). Conclusions FDBD is a frequent phenomenon observed in about 15% of cases, and it was responsible for higher morbidity. Only FD characteristics (DFT and FD diameter) were independent determinants of FDBD. Future research should focus on the impact of novel braid configurations and materials on braid stability.

Abstract Purpose: Metastatic castration-resistant prostate cancer (mCRPC) resistant to androgen receptor signaling inhibitors (ARSI) is often lethal. Liquid biopsy biomarkers for this deadly form of disease remain under investigation, and underpinning mechanisms remain ill-understood. Experimental Design: We applied targeted cell-free DNA (cfDNA) sequencing to 126 patients with mCRPC from three academic cancer centers and separately performed genome-wide cfDNA methylation sequencing on 43 plasma samples collected prior to the initiation of first-line ARSI treatment. To analyze the genome-wide sequencing data, we performed nucleosome positioning and differential methylated region analysis. We additionally analyzed single-cell and bulk RNA sequencing data from 14 and 80 patients with mCRPC, respectively, to develop and validate a stem-like signature, which we inferred from cfDNA. Results: Targeted cfDNA sequencing detected AR/enhancer alterations prior to first-line ARSIs that correlated with significantly worse progression-free survival (P = 0.01; HR = 2.12) and overall survival (P = 0.02; HR = 2.48). Plasma methylome analysis revealed that AR/enhancer lethal mCRPC patients have significantly higher promoter-level hypomethylation than AR/enhancer wild-type mCRPC patients (P &lt; 0.0001). Moreover, gene ontology and CytoTRACE analysis of nucleosomally more accessible transcription factors in cfDNA revealed enrichment for stemness-associated transcription factors in patients with lethal mCRPC. The resulting stemness signature was then validated in a completely held-out cohort of 80 patients with mCRPC profiled by tumor RNA sequencing. Conclusions: We analyzed a total of 220 patients with mCRPC, validated the importance of cell-free AR/enhancer alterations as a prognostic biomarker in lethal mCRPC, and showed that the underlying mechanism for lethality involves reprogramming developmental states toward increased stemness. See related commentary by Nawfal et al., p. 7

Background Piecemeal endoscopic mucosal resection (EMR) is an acceptable technique for T1a esophageal adenocarcinoma, but en bloc R0 excision is advocated for T1b disease as it may offer a potential cure and mitigate recurrence. Thus, distinguishing between T1a and T1b disease is imperative under current treatment paradigms. We investigated whether expert Barrett’s endoscopists could make this distinction based on optical evaluation. Methods Endoscopic images of histologically confirmed high grade dysplasia (HGD), T1a, and T1b disease (20 sets for each) were compiled from consecutive patients at a single institution. Each set contained four images including an overview, a close-up in high definition white light, a near-focus magnification image, and a narrow-band image. Experts predicted the histology for each set. Results 19 experts from 8 countries (Australia, USA, Italy, Netherlands, Germany, Canada, Belgium, and Portugal) participated. The majority had been practicing for > 20 years, with a median (interquartile range) annual case volume of 50 (18–75) for Barrett’s EMR and 25 (10–45) for Barrett’s endoscopic submucosal dissection. Esophageal adenocarcinoma (T1a/b) could be distinguished from HGD with a pooled sensitivity of 89.1 % (95 %CI 84.7–93.4). T1b adenocarcinoma could be predicted with a pooled sensitivity of 43.8 % (95 %CI 29.9–57.7). Fleiss’ kappa was 0.421 (95 %CI 0.399–0.442; P < 0.001), indicating fair-to-moderate agreement. Conclusions Expert Barrett’s endoscopists could reliably differentiate T1a/T1b esophageal adenocarcinoma from HGD. Despite fair-to-moderate agreement for T staging, T1b disease could not be reliably distinguished from T1a disease. This may impact clinical decision making and selection of endoscopic techniques.