Citations

Objectives: Pulmonary function tests (PFTs) are essential for diagnosis, management, and follow-up of a wide range of respiratory conditions as they provide quantitative insights into various aspects of lung function. Precision in ordering and scheduling PFTs, like any test, is crucial as errors can lead to misdiagnoses, delayed treatments, unnecessary retesting, inflated healthcare costs, and potentially compromised patient care. Hence, the aim of this quality improvement initiative was to reduce the PFT ordering error rate to below 5% by redesigning the ordering workflow and implementing a standardized order set tailored to specific clinical scenarios. Methods: The quality improvement initiative was implemented from August 2023 to March 2024. Data was collected from the electronic medical record (EMR) using predefined operational definitions to identify incorrect PFT orders and scheduling errors. A redesigned orderset was created to align with specific clinical presentations, including symptoms, suspected diagnosis, confirmed diagnosis, and presurgical evaluation. Scheduling was also restructured to match the expected testing time for each category. Education sessions were conducted with ordering providers, and ongoing feedback loops were established. Results: Among 575 preintervention PFT orders, 130 (22.6%) contained errors. Following implementation, review of 607 postintervention orders showed a reduction in error rates to 4.1%, representing an ∼80% improvement ( P <0.01). There was no increase in unnecessary testing, supporting the effectiveness of the intervention without unintended negative consequences. Conclusions: Implementation of a knowledge-based CDSS with standardized order sets significantly reduced PFT ordering errors and variability, improving guideline adherence and care quality. Continued refinement and integration with evolving technologies are essential for broader applicability.

Introduction: Multitarget stool DNA (mt-sDNA) is a sensitive stool-based test for colorectal cancer (CRC) screening. Limited referral-center data suggest low rates of incident aerodigestive cancers after a positive mt-sDNA and negative colonoscopy; community-based outcomes are unknown. Methods: Retrospective cohort study of adults referred for colonoscopy after positive mt-sDNA in a large community practice (2017–2021). Among patients with negative colonoscopy, we manually recorded post-colonoscopy recommendations, findings if additional colonoscopies had been performed, aerodigestive cancer diagnosis, and last clinical follow-up. Observed cancer incidence was compared with Surveillance, Epidemiology, and End Results (SEER) data. Results: Of 1,176 patients completing colonoscopy after positive mt-sDNA, 328 (28%) had negative findings. Median cohort age was 67 (IQR 59-72) years. Colonoscopy was performed at a median of 53 days after mt-sDNA sample collection. Post-colonoscopy recommendations aligned with multi-society task force (MSTF) guidelines in 59% of patients. Thirty-two patients underwent repeat colonoscopy with a median of 3.5 (1.9-4.4) years later; 2 (6.3%) had advanced serrated lesions, and no CRC was detected. Median clinical follow-up was 4.4 (3.4-5.6) years. Seven patients developed aerodigestive cancers (2 pancreatic, 5 lung), consistent with expected age- and sex-adjusted SEER incidence (n=7.62) (p=0.823). Discussion: In this community cohort, when a positive mt-sDNA was followed by negative colonoscopy, rates of subsequent advanced colorectal neoplasia and aerodigestive cancer were low. Most patients received recommendations for subsequent colonoscopy that were consistent with MSTF guidelines. Findings further support the current MSTF recommendation of no additional evaluation for extra-colonic malignancy in asymptomatic patients after high quality follow-up colonoscopy.

ABSTRACT Pulmonary hypertension (PH) comprises a heterogeneous group of disorders characterized by elevated pressure in the pulmonary arteries. Despite advances in awareness, utilization of non‐invasive screening with echocardiography, increasing number of targeted therapies, and evolving clinical guidelines emphasizing referral to PH specialty centers, barriers to timely diagnosis and treatment persist. Key challenges span patient‐related and system‐level domains that hinder the effective diagnosis, management, and treatment of PH, particularly pulmonary arterial hypertension (PAH). In this article, the obstacles to PH care are examined and actionable recommendations are proposed. By integrating patient‐related and system‐level perspectives, this review provides a framework to bridge persistent gaps in PH care delivery in the United States.

ABSTRACT Background and Objectives Occult intra‐abdominal metastases are identified in approximately 20% of patients with radiographically localized pancreatic ductal adenocarcinoma (PDAC) through staging laparoscopy, as peritoneal cytology is limited in sensitivity. Methylated DNA markers (MDMs) have demonstrated high diagnostic accuracy for PDAC in tumor tissue, blood, and pancreatic secretions. This study assesses the feasibility and diagnostic performance of MDMs in peritoneal lavage fluid collected during staging laparoscopy, comparing their performance to mutant KRAS (m KRAS ) detection. Methods DNA from peritoneal lavage fluid of PDAC patients was analyzed for m KRAS mutations (codons 12, 13, and 61) using droplet‐digital PCR and for 13 MDMs and a reference gene (B3GALT6) using quantitative methylation‐specific PCR. An MDM score was generated from the average signal of the 13 MDMs and evaluated for its ability to detect intra‐abdominal metastases via receiver operator characteristic (ROC) analysis. Results Among 48 patients, 15 (31%) had intra‐abdominal metastases. The MDM score showed 87% sensitivity and 90% specificity (AUC = 0.98), outperforming m KRAS , which showed 40% sensitivity and 85% specificity (AUC = 0.62; p < 0.0001). Conclusions MDMs in peritoneal lavage fluid may enable highly accurate molecular staging of PDAC and warrant validation in larger studies.

Abstract Rationale Transthoracic echocardiography (TTE) is a very useful measure of cardiac function in patients with pulmonary hypertension (PH), along with right heart catheterization, which is considered to be the gold standard of measurement. It is non-invasive, quick and a good screening tool to assess the function of a failing right ventricle against elevated pulmonary pressures. Portopulmonary hypertension (POPH) is defined as PH associated with portal hypertension. The Tricuspid Annular Plane Systolic Excursion to Systolic Pulmonary Artery Pressure (TAPSE/SPAP) ratio has been found to be an effective prognosticator in different subtypes of PH. This study focuses on the role of TAPSE/SPAP ratio in prognosis of patients with POPH undergoing liver transplantation. Methods This was a single-center retrospective study of POPH patients undergoing liver transplantation at Mayo Clinic Florida from June 2003 to December 2023. It included patients with POPH with a mean pulmonary pressure &gt;20 mm Hg undergoing liver transplantation. Patients with incomplete TTE data, coexisting renal failure on dialysis and requiring liver retransplant were excluded. This study included 27 patients. The last TTE report before liver transplantation was used for data analysis. The TAPSE/SPAP ratio was investigated as predictor of all-cause mortality following liver transplant using Cox regression and area under ROC curve. (Brackets contain 95% C.I.) Time to death after liver transplantation was considered. Patients were followed till August 1, 2024. (The correlation of this ratio-TAPSE/SPAP with some catheterization measured pulmonary pressures and indices have been included in Table 1.) Results Among 27 patients, 13 were female, 14 male. The most common causes of liver failure in these patients were non alcoholic fatty liver disease (NASH) and alcoholic liver disease. Rarely, some etiologies like sarcoidosis, autoimmune hepatitis, primary sclerosing cholangitis and hepatitis B/C were present. There were 7 deaths among total of 27 patients. The hazard ratio (HR) of TAPSE/SPAP for overall mortality by Cox regression was 0.01 (0.00-0.58), p = 0.03. The area under ROC curve was 0.76 (0.55-0.96), p = 0.01 [Also for TAPSE alone, the area under ROC curve was 0.74 (0.51-0.97), p = 0.05] Conclusion This study infers that TAPSE/SPAP ratio seems to be a good predictor of survival in POPH patients undergoing liver transplant, with a higher ratio associated with decreased all-cause mortality. It suggests that TAPSE alone might also be a good predictor with higher TAPSE associated with decreased mortality. This abstract is funded by: None

Abstract Rationale Pulmonary hypertension (PH) develops in up to 50% of patients with advanced interstitial lung disease (ILD) and is associated with increased morbidity, mortality, and impaired quality of life. Early recognition is essential, as available therapy for ILD-PH has been shown to improve outcomes. Identifying physiologic markers of PH may facilitate earlier referral for right heart catheterization (RHC) and initiation of targeted treatment. Thus, this study aimed to (1) compare functional parameters between ILD patients with and without RHC-confirmed PH, and (2) assess the applicability of previously proposed ILD-PH screening criteria. Methods We retrospectively analyzed ILD transplant candidates with available pre-transplant pulmonary function tests (FVC%, DLCO%), echocardiographic right-ventricular systolic pressure (RVSP), six-minute walk distance (6MWD) with oxygen requirement, and RHC data. PH was defined according to the 2022 ESC/ERS criteria. Functional parameters were compared between patients with and without PH. Among those without a prior PH diagnosis, screening thresholds derived from previously published tools were applied (RVSP ≥ 35 mmHg, DLCO &lt; 40%, FVC/DLCO &gt; 1.6, 6MWD &lt; 350 m, or oxygen use during 6MWD). Results Of 107 ILD patients evaluated, 90 had complete RHC data (48 ILD-PH, 42 ILD without PH). Group comparisons are summarized in Table 1. Patients with PH had lower DLCO% (median 18.5 [11.5-26.7] vs 26.5 [20.0-34.7], p = 0.08), higher FVC/DLCO ratios (2.68 [2.1-3.4] vs 1.7 [1.4-2.6], p = 0.08), and higher RVSP (55 [39.7-63.2] vs 39.5 [29-48] mmHg, p = 0.002). Oxygen requirement during 6MWD was more frequent in ILD-PH (79.2% vs 61.9%, p = 0.08). Among patients with PH, 38 (79.16%) had no formal diagnosis prior to pre-transplant RHC. Of these cases, all (100%) met ≥3 screening criteria, most commonly DLCO &lt; 40% (n = 38, 100%), FVC/DLCO &gt; 1.6 (n = 37, 97.3%), and 6MWD &lt; 350 m (n = 33, 86.8%). Additionally, 32 patients (84.21%) met ≥4 criteria and 8 (21.05%) met all five criteria. Conclusion In ILD transplant candidates, patients with PH had worse functional profiles when compared to those without PH, and nearly 80% of PH cases were previously undiagnosed. Systematic application of validated PH screening tools in ILD populations may facilitate earlier recognition, potentially improving patient outcomes. This abstract is funded by: None

Abstract Rationale Treatment of hematologic malignancies has been revolutionized by Chimeric antigen receptor T -cell (CAR-T) therapy. Pulmonary complications are increasingly being reported, however, there are no standardized timelines for pulmonary function test (PFTs) assessment before or after the infusion. We aimed to evaluate changes in lung function (TLC, RV, FEV1, and FEV1/FVC) pre- and post-CAR-T therapy and examine whether these parameters correlate with the development of specific pulmonary complications. Methods We conducted a retrospective chart review of patients above the age of 18 with any malignancy who received CAR-T therapy between June 12, 2018, and December 26, 2023. Pre-CAR-T PFTs were obtained closest to the infusion date, and post-CAR-T PFTs were recorded at the earliest available time following infusion. Pre- and post-CART pulmonary function tests were compared using non-parametric paired tests. In addition, we examined the relationship between baseline PFTs and the subsequent occurrence of pulmonary complications after CAR-T infusion. The Wilcoxon signed-rank test was applied to assess both the magnitude and direction of change while Sign test was used to evaluate only the direction to confirm the consistency of results. These tests were chosen due to small sample size and non-normal distribution of data. Results Among the 68 patients in our cohort, paired pre- and post- CAR-T measurements of pulmonary function were available for 18 patients. FEV1 declined significantly post-infusion (2.70 ± 0.81 L vs 2.28 ± 0.74 L; Z= -2.55, p = 0.011), the FEV1/FVC ratio remained stable (77.8 ± 8.0 vs 80.9 ± 12.2, p = 0.53). Mean TLC and RV remained stable (TLC 5.70 ± 1.18 L vs 4.66 ± 1.02 L, p = 0.17 and 2.13 ± 0.62 L vs 2.00 ± 0.70 L, p = 0.58). There was no significant correlation between the baseline lung function and the development of pulmonary complications. Conclusion Only the pattern of FEV1 decline following CAR-T therapy infusion demonstrates a significant decline, whereas other PFTs, although reduced, did not show significance. While these findings may suggest a restrictive ventilatory pattern, additional data on lung volumes are required to accurately characterize the underlying type of pulmonary function impairment. Although limited by small sample size and non-uniform timing of PFT assessments, this highlights the need for a routine pre-CAR-T pulmonary function evaluation to inform patient selection and baseline risk stratification. This abstract is funded by: None

Abstract Rationale Lymphangioleiomyomatosis (LAM) is a rare, progressive, cystic lung disease affecting women. Sirolimus has been shown to stabilize lung function in women with LAM, but real-world data on long-term safety and efficacy are limited. Methods The NIH Multicenter Safety and Durability of Sirolimus for LAM (MIDAS, NCT02432560) observational registry was launched in 2015. All adult (≥18 years) women with LAM (treated or untreated) were eligible to enroll at any of the 20 U.S. sites and followed longitudinally with serial assessments of lung function, health-related quality of life, and treatment related adverse event (TRAEs). Baseline cohort characteristics and TRAEs are summarized using descriptive analyses. Marginal structural models (MSMs) with inverse probability of treatment weighting estimated the causal effect of sirolimus on annualized forced expiratory volume in one-second (FEV1) decline, adjusting for age at LAM diagnosis, prior treatment with sirolimus, menopausal status, race, presence of angiomyolipomas, supplemental oxygen use; time-varying covariates included diffusing capacity for carbon monoxide (DLCO) and serum vascular endothelial growth factor-D (VEGF-D) levels. Results Longitudinal data was available in 350 LAM patients, most of whom (246, 70.3%) had sporadic LAM. The median age at the baseline pulmonary function test (PFT) measurement was 46 years (range: 19 - 74) and the median (IQR) number of serial PFTs obtained per patient was 3 (1 - 5). The average follow-up duration per patient was 2.8 years. Over half of the patients (196, 56%) were treated with sirolimus during the MIDAS observation period for a median (IQR) treatment duration of 4.9 (2.4 - 7.5) years. MSM analysis demonstrated that sirolimus treatment was durably effective and reduced FEV₁ decline by 74.36 mL/year (95% CI: 15.87 - 132.85) compared with no treatment (-85.31 mL/year for the untreated group vs. -10.95 mL/year for the treated group, p = 0.01). Sirolimus was generally well tolerated; treatment interruption ≥3 months was observed in 38 (19.4%) of the 196 sirolimus treated patients. Logistic regression analysis showed that higher levels of FEV1 (odds ratio: OR = 3.12 [1.45 - 7.11], p = 0.005), VEGF-D (OR = 1.0007 [1.0004 - 1.001], p &lt; 0.001), and DLCO (OR = 1.023 [1.0053 - 1.0413, p = 0.01]), were associated with treatment interruption. Conclusions In the MIDAS cohort, sirolimus treatment resulted in durable stabilization of lung function with a favorable safety profile over a 5-year period. These real-world data support sirolimus as a chronic suppressive therapy for LAM, demonstrating durable efficacy in slowing lung disease progression and tolerability with long-term use. This abstract is funded by: National Institutes of Health

Abstract Introduction The World Health Organization (WHO) has categorized pulmonary hypertension (PH) in five groups. Obstructive sleep apnea (OSA) is an independent cause of group 3 PH. The prevalence of OSA in PH patients is approximately 20% and untreated OSA may contribute to pulmonary vascular remodeling, exacerbating PH. Regular use of positive airway pressure (PAP) can improve pulmonary artery pressures. We hypothesized that untreated OSA is associated with mortality in all five groups of PH, and that mortality is reduced with PAP therapy. Methods We performed a retrospective chart review of the PH patient registry at Mayo Clinic Jacksonville, comprised of 696 patients classified per WHO classification of PH. Mortality in each WHO group of PH was abstracted as well as the presence of OSA as a comorbidity. Compliance with positive airway pressure therapy (PAP) was assessed across all patients with OSA. Results Patients in the registry were followed for a mean of 101.2 months. The mortality across all groups was 36.8%, ranging from 22.6% in group 4 to 64.3% in group 5. OSA was present in 46.9% patients, and it ranged from 33% in group 5 to 58% in group 2. Mortality did not vary significantly in the patients with OSA versus those without OSA (p=0.56). Of patients with OSA, 45.9% was deemed compliant with PAP therapy. Overall, the compliant patients had reduced mortality compared to the noncompliant ones (p=0.045), however this significance was due to pronounced effect in group 1 patients only. Conclusion Almost half of PH patients from our registry had OSA. Compliance with PAP therapy was associated with lesser mortality, primarily due to the effect seen in Group 1 PH patients. Support (if any)

Abstract INTRODUCTION: Colorectal cancer (CRC) is the 2nd most fatal cancer in the U.S.; most benefits of CRC screening are from detection of advanced pre-cancerous lesions (APLs). With a goal to improve non-invasive stool test APL sensitivity, we sought novel APL signatures in stool metaproteomes (host- and gut microbiome-derived proteins) among cancer-free controls (CTRL), APL, and CRC patients. Since dysbiosis in gut microbiota is associated with CRC initiation, we also examined the microbial source of differentially expressed proteins (DEPs). METHODS: Mass spectrometry was performed on archival stool supernatants (n=63 patients; 15 CTRL, 32 APL [16 adenomas & 16 sessile serrated lesions], 16 CRC). A sectioning and database-enrichment strategy was applied for peptide-spectrum matching. Microbial and human-derived proteins were searched against the Integrated Gene Catalogue (IGC) and UniProt human reference proteome. DEPs were identified using thresholds of P &lt; 0.05 and fold-change ≥ 1.5. Pathway annotation of human DEPs was performed with the REVIGO webserver, while gut microbial DEPs were functionally categorized using the KEGG Automatic Annotation Server (KAAS). To assess the taxonomic distribution of microbial DEPs, sequences were aligned against the NCBI non-redundant database using BLASTP. RESULTS: Mass spectrometry detected 879 human and 32,514 microbiome-derived proteins. When limiting detection to proteins present in ≥ 75% of patients, only 117 human and 204 microbial proteins remained. There were 17 (4,875), 288 (9,638), and 63 (3,053) unique human (microbial) proteins detected in CTRL, APL, and CRC groups, respectively. When the protein presence cutoff was set at &gt;30% of patients, there were 52 (13 human [11 upregulated, 2 downregulated], 39 microbial [28 upregulated, 11 downregulated]) DEPs detected for the CRC + APL vs CTRL comparison. Some pathways associated with upregulated human DEPs included: inflammatory response, cellular response to iron, and endothelial cell migration. The top upregulated microbial DEPs were derived from the Phocaeicola, Lachnospiraceae, and Oscillospiraceae genera. The top downregulated microbial DEPs belonged to the Bacteroides, Eubacterium, Agathobacter, Coprococcus, and Blautia genera. CONCLUSION: This work highlights the biological diversity and molecular heterogeneity of the stool proteome. We identified several host and microbial protein markers that differentiate APLs and early CRC from controls. These results provide a foundation for future validation studies, which are necessary to determine the clinical utility of these protein biomarkers prior to their integration into a noninvasive stool test. Citation Format: Emmalee J. Northrop-Albrecht, Vinod K. Gupta, William R. Taylor, Jason P. Sinnwell, Doug W. Mahoney, Patrick H. Foote, Kelli N. Burger, Jaeyun Sung, John B. Kisiel, . Comprehensive investigation of stool metaproteomes among patients with precancerous lesions and colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7656.