Cook County Health and Hospitals System

Abstract Background Infection represents a significant health burden affecting all patient demographics, and thousands of pathogens are known to cause infections in humans; however, many pathogens may not be identified using traditional diagnostic methods. This limitation arises partly from the challenges of growing organisms in conventional culture media, and when employing PCR, the requirement for sequence-specific amplification complicates matters. To overcome these obstacles, in recent years, plasma cell-free metagenomic next-generation sequencing (NGS) has emerged as a noninvasive method to identify and quantify pathogen DNA in plasma. We aimed to gather insights on the clinical use of NGS from both Infectious Diseases (ID) and Non-ID providers.Table 1:Demographics and Question Responses of Perspectives of Next-generation Sequencing Serologic Tests Among All Participants Page 1Table 1:Demographics and Question Responses of Perspectives of Next-generation Sequencing Serologic Tests Among All Participants Page 2 Methods From October 1-November 30, 2024, we conducted a cross-sectional survey among USA and Canadian providers using a purpose-driven sampling among national ID and internal medicine society membership databases. Questions related to NGS use in specific scenarios (Supplemental Document 1). 6 weekly email reminders were sent.Table 2:Comparison of Clinical Utilization Perspectives and Practices of Next-generation Sequencing Serologic Tests Between Infectious Diseases and Non-Infectious Diseases Providers Page 1Table 2:Comparison of Clinical Utilization Perspectives and Practices of Next-generation Sequencing Serologic Tests Between Infectious Diseases and Non-Infectious Diseases Providers Page 2 Results 55 participants initiated the survey, and 34 reported using NGS and completed the remainder of the survey. There most common specialties represented were adult ID (33%), pediatric hematology-oncology (33%), and pediatric ID (18%). The median age was 39 years (IQR 33-54), and 63.6% were female. 81.8% participants were from academic centers (Table 1). Compared to Non-ID providers, ID specialists were older (Median age 33 v. 44, p < 0.04) more likely to have ordered NGS in the past (85% v. 46%, p-value < 0.01), and less likely to order for infection surveillance/pre-emptive therapy in an at-risk population (0% v. 8.8%, p-value < 0.01; Table 2). Conclusion Our cross-sectional survey revealed notable differences among providers regarding specific applications of NGS in clinical care. Although limited by a low response rate and survey completion percentage, this preliminary data could inform the development of enhanced NGS assessment projects. These insights may illuminate the use of NGS and influence future implementation and cost-effectiveness studies. Disclosures All Authors: No reported disclosures

Abstract Background The Cook County Department of Public Health (CCDPH) Suburban Tuberculosis program receives community referrals for TB infection (TBI) from across the Chicago metropolitan area. Over 90% of clients are non–US-born, including many recently arrived refugees and asylum seekers who face barriers to adherence and long-term follow-up. The WHO recommends one month of daily isoniazid and rifapentine (1HP) as an acceptable short-course regimen for TB preventive therapy (TPT). We describe CCDPH’s 2024 experience incorporating 1HP for TBI.Figure 1.TB infection treatment cascade at CCDPH Suburban TB ClinicsFigure 2.Rates of TPT prescription and verified completion rates if prescribed, by new arrival status Methods We conducted retrospective chart reviews of all clients seen for TBI consultation at CCH Suburban TB Clinics from January–August 2024, abstracting demographics, clinical characteristics, and treatment outcomes. We compared clients receiving 1HP versus other regimens—3HP (3 months weekly isoniazid/rifapentine), 4R (4 months daily rifampin), and others—using Wilcoxon Rank Sum and Fisher’s exact tests. Logistic regression evaluated factors associated with treatment completion. New arrival status was defined as immigration from a WHO Region of the Americas country after 2021.Table 1.Characteristics and treatment outcomes among clients prescribed Short Course or Conventional Regimens for TPTTable 2.Factors associated with verified treatment completion Results 289 clients were evaluated, 112 (39%) with new arrival status. All had positive TB tests or contact with an active case. TPT was prescribed to 225 (77.8%): 21 received 1HP (9.3%), 58 received 3HP (26.0%), 140 received 4R (62.2%), and 4 other regimens (1.8%). Of those prescribed TPT, 147 of 224 (66%) completed therapy. Completion was 57% for 1HP vs. 67% for others (p = 0.62); 1HP patients more often reported adverse symptoms (43% vs. 27%, p = 0.028). Follow-up with a prescriber within 30 days (OR 2.25, 95% CI 1.49–5.37) or ≥1 nursing phone contact (OR 8.34, 95% CI 4.03–17.26) increased completion likelihood; new arrival status was negatively associated with completion (OR 0.37, 95% CI 0.21–0.65). Conclusion 1HP was a feasible addition to CCDPH’s program, with completion rates comparable to other regimens. Though adverse symptoms were more common with 1HP, they were mostly tolerable and led to discontinuation in only one case. Early follow-up with a prescriber and engagement through nursing contact were strongly associated with improved treatment completion, suggesting key opportunities to enhance adherence across all regimens. Disclosures All Authors: No reported disclosures

Background This study assessed the effectiveness and safety of patisiran in patients with V122I/T60A variant transthyretin (ATTRv) amyloidosis with polyneuropathy. These variants have been under-represented in previous trials of gene-silencing agents. Methods This was a multicenter, phase IV study conducted at 27 sites in the USA. Patients were ≥ 18 years, diagnosed with ATTRv amyloidosis with polyneuropathy and a documented V122I or T60A variant. Patisiran-treated patients were enrolled prospectively, ambispectively, and retrospectively. The primary endpoint was the proportion of patients with a stable or improved polyneuropathy disability (PND) score at 12 months vs. baseline. Safety was monitored throughout the trial. Results Sixty-seven patients were enrolled, of whom 58 received ≥ 1 dose of patisiran. In the efficacy population, 42/45 (93.3%) patients demonstrated stable or improved PND scores from baseline to Month 12. Patients also showed stable or improved quality of life, health status, autonomic symptoms, and cardiac function vs. baseline. Adverse events occurred in 13/42 (31.0%) patients in the prospective and ambispective cohorts; most were mild or moderate. No deaths or cardiac hospitalizations were considered related to patisiran. Conclusions Patisiran demonstrated a consistent positive effect across multiple endpoints in patients with V122I/T60A ATTRv amyloidosis, including polyneuropathy manifestations.

BackgroundHealth determinants such as income and employment significantly influence declarative memory in women with HIV (WWH). These social exposures may contribute to cognitive decline through complex biological mechanisms. We used high‐throughput metabolomics data and causal mediation analysis to identify multiple biological pathways linking adverse socioeconomic conditions and cognitive decline.MethodA total of 324 women (n = 225 WWH) from the New York sites of the Women’s Interagency HIV Study completed biennial cognitive testing, starting in 2009 and every two years, which included the Hopkins Verbal Learning Test (HVLT)‐R, a measure of verbal learning and memory. Metabolomic assessment was conducted from serum samples collected prior to or at first cognitive visit using liquid chromatography tandem mass spectrometry. We used multivariable generalized estimating equation models to link peripheral metabolomic profiles and cognitive trajectories in verbal learning and memory. Linear mixed effect models were used to predict subject‐specific trajectories for downstream mediation models. We used regression‐based multiple mediation analyses to estimate the joint effect of multiple metabolic mediators as pathways between income, employment, and cognitive trajectories. We considered a false discovery rate (FDR) of 5% for metabolomic discovery.ResultOur sample had average age of 43.1 years and were followed‐up for 11.9 years, 63% were non‐Hispanic Black, 76% reported earnings of <24K, and 65% were unemployed. We identified 16 FDR‐corrected metabolites associated with trajectories in verbal memory and 15 with verbal learning. Top metabolites (serotonin, taurine, adenosine, niacinamide, α‐glycerophosphocholine, ADMA, pseudouridine, and sphingomyelins) were common in both domains. Stratified models by serostatus indicated similar results in WWH and women without HIV. In causal mediation analysis, we found that 30% (95%CI: 4%‐100%) of the effect of employment and 18.2% (95%CI: ‐2.1% to 72.3%) of the effect of income on verbal learning was mediated through differences in metabolite levels. We also found that 35.6% (2.7%‐100%) of the effect of employment and 25.4% (95%CI: ‐1.7%‐100%) of the effect of income on verbal memory was mediated through altered metabolomic signatures.ConclusionHealth determinants influence biological process implicated in cognitive decline. Biosocial interventions are needed to address the conditions that perpetuate poor cognitive health in women.

Background: Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. Ventricular arrhythmias (VAs), including ventricular tachycardia and ventricular fibrillation, are often life-threatening in setting of AMI. While advances in revascularization have improved outcomes, the burden of AMI and VA-related mortality across U.S. subpopulations remains unclear. We aimed to assess trends and demographic disparities in AMI and VA-related deaths in the United States. Methods: We analyzed national mortality data from the CDC WONDER database between 1999 and 2020. Deaths attributed to AMI and VAs were identified using ICD codes. Age-adjusted mortality rates (AAMRs) per 100,000 population and 95% confidence intervals (CIs) were calculated and stratified by sex, race/ethnicity, age group, and geographic region. Results: A total of 71,036 deaths were attributed to AMI and VAs over the study period. The AAMR declined sharply from 2.41 in 1999 to 1.08 in 2007 (APC: -9.91; 95% CI: -10.7 to -9.02). From 2007 to 2020, a gradual decline in mortality was observed (1.08 to 1.01) (APC: -0.83; 95% CI: -1.47 to -0.19). Men had consistently higher AAMR than women from 1999 (4.39 vs 1.88) to 2020 (1.84 v s0.68); moreover, since 2008, no significant decline in mortality was observed for males. Whites had the highest number of deaths (n=62,157; AAMR: 1.51 [95% CI: 1.50–1.52]), followed by Blacks or African Americans (1.43 [95% CI: 1.39–1.46]), American Indians (1.10 [95% CI: 0.98–1.22]), Hispanics (1.04 [95% CI: 1.00–1.07]), and Asian or Pacific Islanders (0.89 [95% CI: 0.85–0.94]). All races had a significant decline in mortality across years; however, Hispanics had a rise in mortality from 2011-2020 (APC: 3.06; 95% CI: 0.82 to 5.36). Mortality increased markedly with age: older adults (≥65 years) had a 49-fold higher AAMR (5.38 vs 0.11) compared to younger adults. There was also a significant state-wide difference in mortality as shown in Figure 1. Conclusion: AMI and VA-related mortality in the US from 1999–2020 remained substantial, with significant disparities by age, sex, race, and region. Older adults, males, and those residing in the South experienced the highest mortality burden. Hispanic had a increase in mortality since 2011. These findings underscore the continued need for targeted prevention, early recognition of electrical complications of AMI, improved post-AMI surveillance, and equitable access to life-saving interventions like ICDs.

Background: Patent foramen ovale (PFO) is a recognized contributor to embolic stroke, especially in hypercoagulable states (HCSs). However, patients with HCSs, including malignancy, were excluded from major PFO closure trials, creating a significant evidence gap. Objectives: This narrative review examines the role of PFO closure in secondary stroke prevention among patients with HCSs, including malignancy. We highlight key studies and current evidence in this understudied population. Methods: A systematic search of PubMed was conducted using pertinent MeSH terms. Due to limited data, a narrative synthesis of the literature was performed. Case Presentation and Narrative Review of Literature: A 43-year-old lady with a history of metastatic breast cancer and recent bilateral pulmonary emboli on anticoagulation (AC), presented with expressive aphasia. MRI brain confirmed a Broca-area infarct. Biopsy of an expansile pelvic mass yielded a diagnosis of ovarian mucinous cystadenocarcinoma. TEE demonstrated a PFO; an embolic stroke driven by hypercoagulability of malignancy was diagnosed. PFO closure was offered for secondary stroke prevention after risk-benefit discussion, as opposed to AC alone. While early trials (CLOSURE I, PC) showed no benefit of closure, subsequent studies (RESPECT, REDUCE, DEFENSE-PFO) favored it in selected patients, but notably, these trials excluded patients with HCSs and malignancy. The benefit of PFO closure in this population thus comes largely from observational data. Abrahamyan et al. found that PFO closure could be safely offered in patients with thrombophilia to prevent recurrent stroke. Liu et al., in their prospective study, noted that among patients with cryptogenic stroke and thrombophilia, PFO closure lowered the risk of recurrence. Similarly, a retrospective study from Greece found benefit from PFO closure in this population. Buber et al. found that among patients with HCSs and stroke, PFO closure offered a five-fold risk reduction from future CVA/TIA. The Society for Cardiovascular Angiography and Interventions (SCAI) guidelines recommend PFO closure in patients with thrombophilia for secondary stroke prevention (conditional recommendation- low certainty of evidence). Conclusions: Data on PFO closure for secondary stroke prevention in HCSs and malignancy are scant, necessitating individualized decision making. Current evidence supports PFO closure, but future studies are needed specifically in this vulnerable population.

Heart failure (HF) is a growing global health concern, and cirrhosis is an increasingly recognized non-cardiac contributor through mechanisms like volume overload, systemic inflammation, and cirrhotic cardiomyopathy. As the global prevalence of liver disease rises, especially from nonalcoholic fatty liver disease (NAFLD), alcohol use, and viral hepatitis, understanding the burden of HF due to cirrhosis is essential. We estimated the non-fatal burden of HF attributable to cirrhosis across five etiologies—NAFLD, alcohol use, hepatitis C, hepatitis B, and other causes—in 204 countries and territories from 1990 to 2021 using data from the Global Burden of Disease Study 2021. Non-fatal burden was estimated by applying standardized severity distributions and disability weights to the prevalence of each cause to quantify impairment. Age-standardized prevalence rates (ASPRs) and annualized percentage changes (APCs) were calculated by SDI, age, and sex. Future prevalence to 2050 was projected using a log-linear regression model. Between 1990 and 2021, total prevalence counts rose substantially across all cirrhosis subtypes. NAFLD-related HF increased from 9,202 (95% UI: 6,417–12,641) to 30,092 (20,452–42,009); alcohol-related from 35,701 (27,666–45,427) to 82,258 (61,635–108,803); hepatitis C from 47,484 (37,044–60,873) to 92,079 (70,272–120,432); hepatitis B from 59,974 (47,824–74,529) to 112,111 (87,717–142,335); and other causes from 99,977 (77,246–129,309) to 133,311 (102,461–169,414). The highest ASPR increase was seen in low SDI regions (APC: 2.49%), followed by high SDI (2.24%), middle (1.73%), high-middle (1.67%), and low-middle SDI (1.60%) regions. In 2021, children aged 5–9 years exhibited the highest burden within the under-20 group (26,749 cases), while adults aged 65–69 years had the peak burden among older individuals (51,379 cases). Females showed a marginally higher annual growth in total prevalence (APC: 0.79%) and ASPR (0.04%) compared to males (0.78% and 0.01%, respectively). Projections estimate the prevalence of heart failure due to cirrhosis will increase to 788,332 cases globally by 2050. HF attributable to cirrhosis is a growing global health concern with rising prevalence across all etiologies, disproportionately impacting low-SDI regions and older adults. The projected surge by 2050 underscores an urgent need for integrated liver-cardiac care, early detection, and policy interventions targeting modifiable liver disease risk factors.