Singh, A

Abstract Rationale Pulmonary hypertension (PH) is a progressive, heterogeneous group of disorders leading to right heart failure and death. Despite advances in management, population-level mortality trends among older adults remain poorly characterized. Understanding these long-term trends is essential for designing equitable, population based interventions. Methods We analyzed mortality data for adults aged 65 years and above using the CDC WONDER database from 1999 to 2020. PH related deaths were identified using ICD 10 codes (I27.0, I27.2,I27.8,I27.9). Age adjusted mortality rates (AAMR) per 100,000 population were calculated and stratified by sex, race and comorbid conditions including hypertension, type 2 diabetes mellitus and congestive heart failure. Temporal trends were evaluated using joinpoint analysis to estimate average annual percent change (AAPC) with corresponding p-values. Results From 1999 to 2020, a total of 141,243 PH related deaths occurred among US adults aged 65 years and above, corresponding to an overall AAMR of 9.1 per 100,000 (95% CI, 8.9-9.3). Annual mortality increased from 5.2 in 1999 to 13.4 in 2020, a 2.6-fold rise (AAPC +3.8%; p < 0.001). Females accounted for 63.7% of all PH deaths and had higher mortality than males (10.8 vs 7.2 per 100,000). Black individuals experienced the highest mortality (12.5 per 100,000), exceeding rates among White (8.7) and Hispanic (7.9) counterparts. The proportion of PH deaths associated with cardiometabolic comorbidities rose substantially, with the largest annual increase seen in PH with coexisting HTN (+4.9% per year), followed by CHF (+4.6%) and T2DM (+4.1%). Conclusions Despite therapeutic progress, overall PH related mortality among older U.S. adults rose significantly from 1999 to 2020. Persistent sex and race based disparities highlight inequities in disease burden and access to care. The increasing coexistence of cardiometabolic comorbidities suggests evolving pathophysiology and emphasizes the need for prevention focused, multidisciplinary strategies. Future work should explore modifiable risk factors and healthcare system determinants driving these trends to inform targeted public health and policy interventions. This abstract is funded by: None

Abstract Rationale High and intermediate risk pulmonary embolism (PE) contributes significantly to in hospital morbidity and 5-10% of in hospital deaths. Thrombolytic therapy either via systemic intravenous tissue plasminogen activator (IV-tPA) or catheter directed thrombolysis (CDT) remains central to management, however, comparative national data on utilization and outcomes of thrombolytic therapy for PE remain limited. Methods Using the National Inpatient Sample data from 2010 to 2021, adult hospitalizations for acute PE were identified using ICD 9 code 415.1 and ICD 10 code I26. Cases receiving IV-tPA or CDT were identified using procedural codes. Temporal trends, in-hospital mortality, length of stay (LOS) and complications were compared between treatment groups using weighted analyses. Results Among 1,940,718 hospitalizations with acute pulmonary embolism, the use of thrombolytic therapy increased from 2010 to 2021 for both systemic intravenous tissue plasminogen activator (IV-tPA) and catheter-directed thrombolysis (CDT). Utilization of IV-tPA rose from 1.8% to 2.%, while CDT increased from 1.4% to 3.9%. Compared to IV-tPA, patients treated with CDT were more likely to be older (42.7% vs 39.3% were aged 65 years or above) and male (50.8% vs 48.7%). CDT was associated with significantly lower in hospital mortality (6.7% versus 11.1%, p < 0.01), shorter median length of stay (5 versus 6 days, p < 0.01) and fewer discharges to facilities (13.7% versus 19.4 %, p < 0.01). Rates of major complications were lower in the CDT group, including intracranial hemorrhage (0.4% versus 1.2%), cardiac arrest (1.7% versus 7.3%), myocardial infarction (4.7% versus 5.1%) and need for mechanical ventilation (6.7% versus 16.1%). However, use of extracorporeal membrane oxygenation (0.7% versus 0.2 %) and surgical embolectomy (1.2% versus 0.7%) was higher among CDT patients. Conclusions From 2010 to 2021, utilization of thrombolytic therapy, particularly catheter-directed techniques increased among PE hospitalizations. CDT was associated with lower in hospital mortality, shorter stays and fewer complications compared to systemic IV-tPA. These findings support the expanding role of catheter based interventions as a preferred therapeutic approach for patients with high and intermediate risk pulmonary embolism. Further prospective studies are warranted to confirm long term outcomes and optimize patient selection for CDT. This abstract is funded by: None

Abstract Rationale The diagnosis of interstitial lung disease (ILD) requires a multidisciplinary discussion (MDD), in which high-resolution computed tomography (HRCT) and histopathology play key roles. Genomic classifiers have recently been introduced for clinical use, in which lung tissue obtained via transbronchial forceps biopsy undergoes whole-transcriptome RNA sequencing followed by gene expression analysis. These molecular tools are particularly valuable in establishing a diagnosis of idiopathic pulmonary fibrosis (IPF) in patients without a definite usual interstitial pneumonia (UIP) pattern on imaging. Although genomic classifiers are increasingly utilized in clinical practice, data on their diagnostic performance continue to evolve, warranting an updated analysis of the current evidence. Methods A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Comprehensive search of PubMed, MEDLINE, Embase, Scopus and the Cochrane Library were performed through October 2025 using predefined terms including “genomic classifier,” “Envisia,” “UIP,” and “interstitial lung disease.” Eligible studies were which enrolled adult patients with ILD of uncertain etiology in whom genomic classifiers were compared with histopathologic or MDD based reference standards. True positive, false positive, false negative, and true negative data were extracted to calculate pooled estimates of sensitivity, specificity and the area under the receiver-operating characteristic curve (AUROC) using a random-effects bivariate model. Results Six studies comprising 347 patients met inclusion criteria, with sample sizes ranging from 24 to 98 participants. Across studies, sensitivity ranged from 59% to 85% and specificity from 75% to 100%. The pooled sensitivity was 68% (95% CI, 60-76%; P < 0.001) and specificity 77% (95% CI, 70-85%; P < 0.001), with an estimated AUROC of 0.73 (95% CI, 0.65-0.81) indicating discriminative performance. In two studies evaluating clinical impact, incorporation of genomic classifier data into MDD increased diagnostic confidence in ILD subtyping by 30-50%. No major adverse events related to transbronchial tissue acquisition were reported. Conclusions Genomic classifiers represent a promising, less invasive adjunct for identifying UIP patterns in ILD, demonstrating good overall diagnostic accuracy. Incorporating classifier results within MDD frameworks enhances diagnostic confidence and may reduce the need for surgical lung biopsy in appropriately selected patients. However, small study sizes, potential funding bias and limited accessibility highlight the need for larger, independently conducted prospective studies to further define their role in future IPF diagnostic algorithms. This abstract is funded by: None

Abstract Introduction Aminoglycoside antibiotics are well known to cause cochlear and vestibular toxicity when used systemically. Inhaled tobramycin was developed to reduce systemic exposure and is considered safer with only rare reports of ototoxicity have been reported in patients with renal dysfunction. We describe a case of bilateral sensorineural hearing loss (SNHL) and tinnitus associated with inhaled tobramycin in a patient without renal impairment, emphasizing that even inhaled formulations can induce significant auditory toxicity in susceptible individuals. Case A 85 year old woman with Sjogren’s related interstitial lung disease and bronchiectasis who was chronically colonized by Pseudomonas aeruginosa was treated with inhaled tobramycin for recurrent infections. She had normal renal function and no prior aminoglycoside exposure. After approximately three months of inhaled therapy, she noted progressive bilateral hearing decline and high pitched tinnitus without vertigo or otalgia. Physical examination revealed clear ear canals and intact tympanic membranes. Baseline audiometry one year ago had demonstrated mild to moderately-severe bilateral SNHL. Repeat testing after tobramycin exposure showed worsening thresholds and reduced word recognition bilaterally. MRI of the brain and internal auditory canals was unremarkable. Serum creatinine remained normal throughout treatment. Inhaled tobramycin was discontinued, after which hearing loss stabilized. No further progression was observed on follow-up audiometry. Discussion Although systemic absorption from inhaled tobramycin is typically low, elderly and low-body-weight patients may accumulate sufficient serum levels to cause cochlear injury. Mechanisms include reactive oxygen species mediated hair cell toxicity and possible genetic susceptibility involving the mitochondrial 12S rRNA mutation. Prior reports of vestibulotoxicity and cochleotoxicity from inhaled tobramycin primarily involved patients with renal dysfunction, however, this case report demonstrates that toxicity can occur despite preserved renal function. Clinicians should maintain vigilance for otologic symptoms in patients receiving inhaled aminoglycosides. Baseline and periodic audiometric monitoring should be incorporated into chronic treatment protocols. This abstract is funded by: None