Citations

Abstract Rationale The United States has the highest per capita incarceration rate of any developed democracy. As the incarcerated population ages, medically complex and frail patients are increasingly hospitalized in the community, often arriving without decisional capacity and with limited family involvement. This is the first analysis of state laws and policies governing decision-making for incapacitated incarcerated patients. Methods Two team members independently conducted Westlaw and Internet searches for statutes, regulations and department of corrections (DOC) policies from 50 states and the District of Columbia, identifying language about medical decision-making for incapacitated incarcerated patients. These parallel searches were merged into a single database and reviewed by the analytic team, who created a codebook of inductively and deductively derived themes, guided by principles of grounded theory. The codebook was then systematically applied to the database by 2 independent coders; all data were double-coded. Disputes were resolved by consensus with the entire analytic team, in consultation with a legal scholar. Results Thirty-four of 51 jurisdictions have language addressing decision-making for incapacitated incarcerated patients. Data collected include the definition and determination of incapacity, language affirming incarcerated persons’ right to autonomy in medical decision-making, approaches to decision-making for patients with and without surrogate decision-makers, and whether treatment over patient/surrogate objection is authorized. Assertions about the importance of advance care planning (n = 25) are often undercut by procedural hurdles (n = 20), such as complex witnessing requirements for advance directive completion. Many jurisdictions (n = 26) allow family or friends to serve as legally recognized decision-makers. Thirteen jurisdictions exclude an incarcerated person from serving as decision-maker for another incarcerated person. Fourteen jurisdictions have provisions allowing for treatment over the objection of a patient or their surrogate. While approaches to unrepresented patients differ widely (Figure), 5 jurisdictions grant narrow decisional authority to treating physicians and 4 jurisdictions authorize correctional employees to make medical decisions. Conclusion A heterogeneous assortment of laws, policies and regulations govern the care of incapacitated incarcerated patients, with wide variation observed from jurisdiction to jurisdiction. One-third of jurisdictions lack policies or language regarding decision-making processes for incapacitated incarcerated patients. Even more troubling, 14 jurisdictions allow treatment over a patient or surrogate’s objection and 4 jurisdictions delegate authority over decisions for unrepresented patients to correctional employees, such as the prison medical director or the warden. These findings raise serious concerns about autonomy, beneficence and justice. National reform is needed to align correctional policies with established ethical standards for surrogate decision-making. This abstract is funded by: National Institute on Aging

Abstract Introduction The COVID-19 pandemic exposed underrecognized structural deficiencies in pandemic preparedness across the US, particularly impacting marginalized and medically vulnerable populations. State leaders who were developing policies to allocate critical care resources, often called crisis standards of care (CSC), confronted challenges such as whether and how to incorporate age and chronic conditions into triage protocols, how to contend with imperfect illness acuity scores such as the sequential organ failure assessment (SOFA), and whether essential worker status or area deprivation index (ADI) ought to confer an advantage during triage. To our knowledge, this is the first analysis to highlight CSC writers’ approach to ethical challenges, including from states whose policies provoked corrective action from the Office of Civil Rights (OCR). This study explores how state leaders navigated ethical controversies underlying states’ CSC policies, including whether those controversies were satisfactorily resolved. Methods Between February-September 2022 we conducted semi-structured interviews of public health leaders tasked with developing their states’ (CSC) policies. Interviews were transcribed verbatim and a codebook was developed iteratively, using inductively and deductively derived themes based on principles of grounded theory. The codebook was systematically applied to transcripts; disputes were resolved by consensus discussion among analytic team members. Results Leaders from 34 states were interviewed. Participants described how their states’ CSC policy writing committees considered the role of age in triage, some proposing age as a tiebreaker, or considering age only if coupled with measures of frailty or chronic illness, with others proposing age as an “exclusion criterion.” Many leaders acknowledged a controversial approach to disability in early versions of their policies, some describing how they responded to civil rights complaints. Participants described debates over whether pandemic triage decisions should advantage patients from underserved populations or affirmatively consider essential worker status or pregnancy. While most leaders regretted that early iterations of their policies stood to exacerbate health disparities, others described a less conciliatory response to civil rights complaints. In particular, triage exclusion criteria, whereby certain patients would be excluded outright from certain resources, provoked intense debate. Conclusion We describe ethical controversies that stymied CSC policy writing committees during the COVID-19 pandemic. Leaders described spirited debate around how age, disability, and justice ought to factor into triage; few described satisfactory resolution to those debates. Improved community engagement and adherence to civil rights protections in CSC are imperative to protect marginalized populations as we prepare for future calamites, whether global or local. This abstract is funded by: R03 AG73987; K76 AG88403

Abstract Introduction Burkholderia, Achromobacter, and Stenotrophomonas species are associated with worse clinical outcomes in cystic fibrosis (CF),1 though little is known about their prevalence or pathogenicity in non-CF bronchiectasis (pwBE). Herein we describe the prevalence and clinical characteristics of pwBE who isolated each of these three organisms. Methods We conducted a retrospective cross-sectional analysis of baseline data from the US Bronchiectasis and Nontuberculous Mycobacteria (NTM) Research Registry (BRR). Adult bronchiectasis patients with known Achromobacter, Burkholderia cepacia complex (BCC), or Stenotrphomonas maltophilia culture results were included. Patients were stratified according to the presence of at least one positive culture among the gram-negative species. Demographics, clinical characteristics, and first annual follow-up culture results were summarized descriptively for the overall study population and between groups. No inferential analyses or hypothesis testing was performed. Results 5003 pwBE met the inclusion criteria, of which 39 (0.78%) isolated Achromobacter species, 11 isolated Burkholderia (0.22%), and 288 isolated Stenotrophomonas maltophilia (5.8%). Patients with Achromobacter were older, with a median age (interquartile range) of 76 (73.0-79.0) years, compared to the overall bronchiectasis cohort (69.0 years). Those with Burkholderia or Stenotrophomonas were younger, at 69.0 (53.0-75.0) and 71.0 (63.0-77.0) years, respectively. A high proportion of those with Achromobacter were male (31%) versus those with Burkholderia (9%) and Stenotrophomonas (24%), were current or former smokers (46%), were more likely to have had one or more exacerbations in the 2 years prior to enrollment (87%) than the overall BE cohort (57%), and were more likely to have had pulmonary-related hospitalization than those with either Burkholderia or Stenotrophomonas (46% vs. 27% and 19%, respectively). PwBE who isolated Burkholderia were less likely to have co-colonization with Pseudomonas aeruginosa or NTM species (9% each). At first annual follow-up, no patients with baseline Burkholderia isolated them at follow-up, and only 31% with baseline Stenotrophomonas isolated it at follow-up. Conclusion Overall prevalence of Achromobacter, Burkholderia, and Stenotrophomonas species in the BE cohort was low. Patients who isolated Achromobacter species were older, more likely to be current or former smokers, and more likely to experience pulmonary exacerbation and hospitalization. 15 patients who had not previously isolated Achromobacter, and 3 patients who had not previously isolated Burkholderia did so at annual follow-up. Interestingly, no patients with baseline Burkholderia isolates went on to isolate it at annual follow-up, which contradicts earlier studies in pwCF.2 The number of patients isolating Burkholderia in the U.S. BRR is very low, thereby limiting interpretation. This abstract is funded by: None

Abstract Rationale Gastroesophageal reflux disease (GERD) is a common comorbidity in non-cystic fibrosis bronchiectasis (NCFB), yet its impact on clinical outcomes remains poorly defined. We sought to determine whether GERD is associated with worse clinical outcomes in patients with NCFB using a large, real-world database. Methods We conducted a retrospective cohort study using the TriNetX platform, identifying patients with NCFB (ICD-10 J47*) with and without concurrent GERD (ICD-10 K21*), excluding those with cystic fibrosis (ICD-10 E84*). Propensity score matching (PSM) was performed using 1:1 nearest neighbor matching without replacement, controlling for age, sex, race/ethnicity, obesity, socioeconomic risk factors, and tobacco use. Primary outcomes included pneumonia, bronchiectasis exacerbations, intensive care unit admission, mechanical ventilation, and mortality. Statistical analyses included risk ratios and Cox proportional hazards modeling for survival outcomes. Results Out of 421,710 patients with NCFB in the dataset from January 2000 to September 2025, 186,874 (44%) had a diagnosis of GERD. After propensity score matching, 179,753 patients with NCFB+GERD and 179,753 patients with NCFB-only were included (mean age 74.0±13.1 years, 58.8% female, 67.1% White). Baseline characteristics were well-balanced after matching. Median follow-up was approximately 2.5 years for both cohorts (898 vs 889 days; similar means and IQR), ensuring balanced observation time. Compared to NCFB-only, NCFB+GERD was associated with increased risks for mortality (risk ratio 1.04, 95% CI 1.02-1.05; p < 0.001), pneumonia (risk ratio 1.06, 95% CI 1.05-1.08; p < 0.001), bronchiectasis exacerbations (risk ratio 1.03, 95% CI 1.01-1.06; p = 0.006), and mechanical ventilation (risk ratio 1.14, 95% CI 1.10-1.18; p < 0.001). Intensive care unit admission rates were comparable between groups (risk ratio 1.00; p = 0.65). Conclusions In this large propensity score-matched analysis, concurrent GERD in NCFB is independently associated with increased mortality, pneumonia, bronchiectasis exacerbations, and mechanical ventilation requirements. These findings suggest GERD may represent a modifiable risk factor warranting aggressive management in NCFB patients. Study limitations include retrospective design, reliance on ICD-10 coding accuracy, and potential unmeasured confounders. Our results support systematic screening and treatment of GERD in NCFB, but whether targeted GERD management can modify the natural history of NCFB future investigation. This abstract is funded by: None

Abstract Rationale Long COVID (LC) has affected approximately 400 million people worldwide, with about 20 million in the US. LC is characterized by a host of new symptoms, including neuropsychiatric disorders including cognitive impairment. Disruption of the gut microbiome has been correlated with symptoms of LC. This study examined whether gut microbiome modulation via intake of probiotic fermented foods mitigated psychiatric and cognitive impairments. Methods This was a pilot trial performed at a single academic medical center that enrolled and randomized patients with LC 1:1 into the treatment vs. control arm. Those enrolled into the treatment arm received teaching on the gut microbiome, its relationship to LC, and were encouraged to eat a diet high in probiotic fermented foods for 12 weeks. Those in the control arm did not receive the teaching and were encouraged to eat their normal diet. Diets were tracked using the Mayo Clinic Diet application on a smart phone at least three days per week, and those in the treatment arm received routine calls to discuss protocol adherence and gather subjective feedback on the trial. Neuropsychiatric questionnaires (HADS, IES-R, EQ-5D-5L, and MoCA Blind) were completed at enrollment and upon completion of the trial. Questionnaire scores were evaluated for changes using a paired t-test, with statistical significance defined as a p-value <0.05. Correlation between the fermented food intake and improvements in questionnaires was completed using the Spearman test. Results 43 patients were enrolled; 18 patients in the treatment arm and 20 patients in the control arm completed the trial. Groups did not differ by age, race, education, or baseline neuropsychiatric testing. There was a significant increase in fermented food intake in the treatment arm over the duration of the study. Those in the treatment arm had improvements in questionnaires related to anxiety, PTSD, and quality of life. Those in the control arm only had improvements in reported overall quality of life. Intra-group changes can be seen in Table 1. Correlations between fermented food intake and change in questionnaire scoring showed numerical but not statistically significant improvements in many of the questionnaires, except for the MOCA questionnaire and EQ-5D-5L Self-Care question. Conclusion Implementing a diet high in fermented foods in patients with LC appears to have some signal for improvement in neuropsychiatric symptoms. Completing a larger trial would help clarify if changes would be statistically significant. This abstract is funded by: Mayo Clinic Critical Care Research Committee

Abstract Rationale Interstitial lung disease (ILD) affects ∼50% of patients with systemic sclerosis (SSc) and is a leading cause of mortality. Visual assessment of ILD extent and morphologies, including ground-glass opacities (GGO) and reticular densities (RD), suffers from poor interobserver agreement, limiting prognostic consistency. CALIPER Quantitative CT (QCT) provides reproducible volumetric measures of parenchymal and vascular features. This study evaluated baseline QCT-derived lung features for association with transplant/mortality risk in SSc-ILD. Methods A retrospective cohort of SSc patients (≥18 years) seen at an academic center from 2007-2018 was identified using ICD codes, with ACR/EULAR 2013 SSc criteria confirmed by chart review. Inclusion required ILD on high-resolution CT (HRCT) ±2 years of SSc diagnosis, and PFTs ±6 months of HRCT. CALIPER quantified volumes of normal lung, GGO, RD, hyperlucency, honeycombing (HC), and pulmonary vascular-related structures (PVRS), which are expressed as percentages of total lung volume. Right heart catheterization confirmed pulmonary hypertension (PH) defined by 2022 ESC/ERS criteria (Eur Heart J, 2022). Cox hazards models assessed associations with combined mortality/transplant outcome, a priori adjusted for age, sex, diffuse SSc subtype, ILD duration, and PH (Column B), and further adjusted for baseline percent predicted FVC (ppFVC) and ppDLCO (Column C)(Table 1). Results Of 132 SSc-ILD patients, median SSc and ILD disease durations at HRCT were 1.4 (0.6, 2.4) and 0.0 (0.0, 0.5) years. Median feature percentages: total ILD 13.0% (IQR: 6.4, 21.0), GGO 10.2% (4.6, 16.9), RD 1.9% (0.8, 3.7), HC 0.03% (0.00, 0.09), PVRS 3.2% (2.3, 4.1). Median ppFVC was 81.1% (69.4, 92.6), and ppDLCO 60.0% (46.0, 75.7); 21 patients had PH. There were 2 transplants and 45 deaths. Every 5% increase in baseline total ILD and GGO associated with 22% (HR 1.22; 95% CI 1.12-1.33) and 24% (1.24; 1.12-1.36) higher risk of transplant/mortality on unadjusted models (Column A), respectively, remaining significant after a priori (CB) and full adjustment (CC)(Table 1). Every 1% increase in RD and PVRS conferred 19% (1.19; 1.08-1.31) and 33% (1.33; 1.08-1.63) higher risk of transplant/mortality in unadjusted models (CA); RD retained significance after a priori adjustment (1.17; 1.03-1.33), while PVRS trended non-significant in adjusted models. Conclusions In early SSc-ILD, QCT-derived GGO, RD, and PVRS provide robust prognostic value for mortality/transplant risk assessment, with small increases in baseline severity—at or below visual detection thresholds—associating with clinically meaningful risk increases. These findings support integrating baseline QCT biomarkers into risk stratification beyond clinical and PFT measures. This abstract is funded by: Rheumatology Research Foundation

Abstract Rationale Type-1 inflammation in asthma leads to significant airway level changes independent of Type-2 inflammation and may underlie the severity seen in combined Type1/2 high disease. As IFNs can cause airway epithelial injury and impaired repair, we applied a novel interpretable machine learning algorithm, SLIDE, to analyze the transcriptome of airway epithelial brushings of mild-moderate (MMA) and severe asthma (SA) participants in the Immune Mechanisms in Severe Asthma (IMSA) cohort to identify latent/hidden factors of disease that associate with disease severity. Methods The expression of genes identified by SLIDE as part of a co-expression program was assessed in the full IMSA cohort by severity and in an independent cohort of the NHLBI Severe Asthma Research Program (SARP). We also examined associations of these genes with clinical asthma outcomes in both cohorts. Results SLIDE identified aberrant increased expression of membrane-tethered mucin genes, MUC1 and MUC4. MUC1 appeared in each of 5 significant latent factors associated with greater severity and MUC4 in 2/5. Standard DGE analysis also identified the gene CEACAM5 as a predictor of severity. Pathway analysis of latent factor genes revealed airway keratinization which may contribute to airway remodeling and worsening obstruction over time. Expression of MUC1, MUC4, and CEACAM5 were increased in SA compared to HC in both the full IMSA and separate SARP cohorts (p < 0.001 for all genes in both cohorts). Expression in MMA was consistently lower than in SA in both cohorts, reaching significance in IMSA (p < 0.01) but not consistently in SARP (MUC1 p = 0.04, MUC4 p = 0.27, CEACAM5 p = 0.27). Protein analysis of endobronchial biopsies by immunofluorescence staining showed a trend towards increased MUC1 protein content with evidence of secretion. MUC1, MUC4 and CEACAM5 were negatively correlated with FEV1 % predicted in both cohorts (IMSA: MUC1 r=-0.47, p < 0.01, MUC4 r=-0.47, p < 0.01, CEACAM5 r=-0.62, p < 0.01; SARP: MUC1 r=-0.19, p = 0.05, MUC4 r=-0.29, p < 0.01, CEACAM5 r=-0.51, p < 0.01). All three genes positively correlated with prospective exacerbations in both cohorts (IMSA: MUC1 r = 0.345, p = 0.01, MUC4 r = 0.216, p = 0.08, CEACAM5 r = 0.368, p < 0.01; SARP: MUC1 r = 0.22, p = 0.02, MUC4 r = 0.32, p < 0.01, CEACAM5 r = 0.38, p < 0.01). Conclusions The expression of MUC1, MUC4 and CEACAM5 increased with asthma severity in the airway epithelium and correlated with both prospective exacerbations and obstruction. As pathway analysis of genes in the significant latent factors were associated with airway keratinization aberrant expression of these mucins (with known signaling functions) may contribute to maladaptive repair and airway remodeling that drives obstruction over time, contributing to worse asthma outcomes. This abstract is funded by: NIH

Abstract Rationale Asthma is a chronic inflammatory airway disorder influenced by pulmonary and systemic factors. Epidemiologic and experimental data suggest associations between asthma, anemia, and reduced iron stores. Sex may modify this relationship: females, with lower baseline iron reserves, menstrual blood loss, and hormone-mediated immune effects, may exhibit greater susceptibility, whereas males, with higher iron stores and androgen-related anti-inflammatory influences, appear less affected. This study tested the hypothesis that diminished iron stores, rather than anemia itself, are associated with asthma, and that this relationship differs by sex. Methods Data were analyzed from nine consecutive NHANES 2-year cycles (1999-2018), a nationally representative U.S. dataset. Lifetime asthma was defined as a prior physician diagnosis and active asthma as “Do you still have asthma?”. Anemia was defined by WHO criteria (hemoglobin <12 g/dL in females and <13 g/dL in males), and iron deficiency as ferritin <30 ng/mL. Accordingly, iron status was categorized as normal, iron deficiency anemia (IDA), iron deficiency without anemia (IDWA), and anemia without iron deficiency (AWID). Analyses followed NHANES guidelines and were conducted with the SURVEY package in R. Results Female participants were older and had lower eosinophil counts, ferritin, and hemoglobin levels, with a higher prevalence of anemia, lifetime asthma, and current asthma. Similar trends were observed among participants with available ferritin data (Table 1). In unadjusted analyses, ferritin levels were inversely associated with lifetime (β = -0.19; p <0.001) and active asthma (β = -0.35; p <0.001), but these associations were not significant after adjustment for sex, age, BMI, race, and log10-transformed eosinophil count (lifetime: β = 0.03; p = 0.61; active: β = -0.08; p = 0.40). In contrast, anemia was associated with increased odds of lifetime (adjusted OR [95% CI], 1.52 [1.21-1.92]) and active (1.50 [1.13-1.99]) asthma in males, but not in females (0.98 [0.86-1.12] and 0.98 [0.83-1.15], respectively). Among males, AWID was associated with active asthma (2.07 [1.08-3.96]), whereas IDA and IDWA were not. No associations were observed among females. Conclusion The relationship between anemia and asthma may be primarily driven by inflammation related to asthma rather than true iron deficiency. After adjustment, ferritin was not independently associated with asthma, whereas anemia—particularly AWID—remained associated among males. These findings suggest that asthma-associated systemic inflammation contributes to anemia of chronic disease, underscoring the need to distinguish inflammatory anemia from nutritional iron deficiency in research and clinical management. This abstract is funded by: NIH

ABSTRACT Objective This study examines the knowledge, beliefs, and perceptions of asthma among caregivers in Bogotá, Colombia, a middle‐income country (MIC). It provides insights into how these factors influence self‐management and adherence. Methods Trained facilitators conducted focus groups composed of caregivers of asthmatic children. Interview data were analyzed and coded using a process of open coding transcription, followed by inductive thematic‐based coding. The basic codes were then elaborated into a framework of thematic categories within NVivo. Results Sixteen caregivers were divided into two focus groups. Knowledge, beliefs, and perceptions about asthma and inhalation therapy, interactions between caregivers and other individuals, the use of traditional and natural medicine, and the availability of essential medications for asthma therapy were highlighted by the participant caregivers. Although some of the issues identified in these topics are similar to those described in high‐income countries, there are some differences, particularly regarding the fears of patients developing addiction to medications due to the use of inhalation therapy in childhood, the lifelong requirement of inhalation therapy, and the use of traditional versus natural medicine. Conclusions The present study's findings provide insights into how caregivers understand asthma and its treatment in their children. These insights can serve as a basis for more targeted and effective educational interventions in Colombia and other countries with similar socio‐economic and cultural conditions.