Citations

Abstract Rationale To construct multi-trait polygenic scores (PRS) predicting chronic obstructive pulmonary disease (COPD) and exacerbations, validate their performance in diverse cohorts, and identify PRS-related proteins for potential therapeutic targeting. Methods PRSmix+, a multi-trait PRS framework, is used to train a composite PRS (PRSmulti) in COPDGene non-Hispanic white participants (n = 6,647). Associations of PRSmulti with COPD status (GOLD 2-4 vs. GOLD 0 or ICD) and exacerbation frequency were tested in COPDGene African American (n = 2,466), ECLIPSE (n = 1,858), MassGeneral Brigham Biobank (n = 15,152), and All of Us (n = 118,566). Protein prediction models were applied to GWAS summary statistics from traits contributing to PRSmulti and were validated with proteomic data in COPDGene (n = 5,173) and UK Biobank (n = 5,012). Results PRSmix+ selected 7 traits for PRSmulti. In multivariable models, PRSmulti was associated with COPD status (meta-analysis random effects (RE) OR 1.58 [95% CI: 1.28-1.94]) and exacerbation frequency (meta-analysis RE beta 0.21 [95% CI: 0.11-0.31]), with higher effect sizes observed in smoking-enriched cohorts. PRSmulti outperformed traditional single-trait PRS in all tested cohorts. Using protein prediction models, we identified 73 proteins associated with the PRS that were also validated with measured protein levels in COPDGene and UK biobank. Of these proteins, 25 were linked to approved or investigational drugs. Notable targets include AGER (RAGE), IL1RL1, and SCARF2, all implicated in COPD pathogenesis and exacerbations. Conclusions Multi-trait PRS improves prediction of COPD and exacerbation risk. Integration with proteomic data identifies druggable protein targets, offering a promising avenue for precision medicine in COPD management. Trial registration. COPDGene: NCT00608764; ECLIPSE: NCT00292552. This abstract is funded by: NIH and the COPD Foundation

Abstract Introduction Pulmonary artery masses have a broad differential. CT may offer initial characterization, but cardiac MRI and PET/CT provide more definitive information. Histopathologic evaluation is often required. We present a rare case of a pulmonary artery mass with an elevated IgG4 index, initially misclassified as more common benign and malignant entities. Case-Presentation: A 61-year-old never smoking female was referred to the pulmonary clinic for abnormal imaging. Her history was only for patent ductus arteriosus repair in infancy. She initially presented with pleuritic chest pain and was found to have near occlusive mass in the distal main pulmonary artery extending into the proximal left main pulmonary artery. This was presumed to be pulmonary embolism, and anticoagulation was started. At presentation, she reported mild dyspnea and improving chest pain, without constitutional symptoms. Cardiac MRI revealed restricted diffusion and enhancement consistent with pulmonary artery sarcoma. PET-CT revealed FDG avid pulmonary artery mass (SUV max 14.5) without other hypermetabolic lesions. She subsequently underwent resection of the main and proximal left PA mass resection with bovine pericardial reconstruction. Histopathology showed a dense lymphoplasmacytic infiltrate with prominent plasma cell infiltration, IgG4/IgG ratio of 40%, and > 10 IgG4 positive plasma cells per high power field. No histiocytic proliferation or evidence of other atypia. Her serum IgG4 level, CRP, ANCA serology, and fungal serology were normal. Discussion Here we present the case of isolated pulmonary artery mass with elevated IgG4 index of greater than 40% without other organ manifestations of IgG4 related disease (IgG4-RD). Cases of IgG4-RD related infiltration with a pulmonary artery mass have been reported, yet these typically present with other systemic manifestations, vascular inflammation, luminal stenosis, and/or pulmonary hypertension. Based on ACR 2019 IgG4 related disease classification criteria, these patients would not strictly meet criteria for IgG4 related disease. After extensive multidisciplinary discussion, we have elected to hold systemic treatment for IgG4-RD. She will be followed closely, monitoring new evidence of organ infiltration that would warrant systemic treatment. Conclusion Pulmonary artery masses should raise suspicion for various benign etiologies, such as chronic thromboembolism, and malignant entities, including pulmonary artery sarcoma. Cardiac MRI, PET/CT, and histopathology were critical in this patient’s evaluation. IgG4-related disease can rarely present as an intimal pulmonary artery mass. However, this is typically accompanied by systemic findings suggestive of IgG4-RD, other vascular infiltration, and/or pulmonary hypertension, all of which were absent in this patient. This abstract is funded by: None

OBJECTIVE The aim of this study was to evaluate freedom from tumor progression and clinical outcomes in older adults with small- to medium-sized vestibular schwannoma (VS) managed by observation versus stereotactic radiosurgery (SRS) to better inform optimal management in this patient population. METHODS In this international multicenter study, patients aged ≥ 60 years with Koos grade I or II VS managed by observation or SRS were retrospectively reviewed. Propensity score matching was conducted using patient characteristics, tumor size, and hearing assessments. Outcome measures of freedom from tumor progression, serviceable hearing preservation (SHP), and neurological function (tinnitus, vestibulopathy, House-Brackmann grade, and trigeminal nerve function) were assessed for both groups. RESULTS The observation and SRS groups each comprised 51 matched patients (median age 68 years for both). Ipsilateral serviceable hearing was observed at presentation for 35 patients in each group. The median follow-up duration was 39 months in the observation group versus 27 months in the SRS group (p = 0.5). Tumor progression was significantly lower with SRS than with observation (2% vs 52.9%, p < 0.001). The rate of 5-year freedom from tumor progression was 100% in the SRS group versus 43% (95% CI 29%–64%) in the observation group. The rate of 10-year freedom from tumor progression was 90% (95% CI 73%–100%) in the SRS group versus 20% (95% CI 8.5%–49%) in the observation group. At the last follow-up, hearing loss occurred in 42.9% of the observation group and 51.4% of those who underwent SRS (p = 0.5). The 3-year SHP rate was 68% (95% CI 53%–88%) versus 65% (95% CI 49%–85%) (p = 0.8), and the 5-year SHP rate was 53% in both groups (95% CI 36%–78% in the observation group and 95% CI 35%–79% in the SRS group, p = 0.8). The composite endpoint of tumor progression and/or worsened neurological outcome, including hearing loss, tinnitus, vestibulopathy, facial nerve dysfunction (House-Brackmann grade), or trigeminal dysfunction, demonstrated a significantly lower rate in the SRS group (17.6%) compared with the observation group (66.7%) (p < 0.001). CONCLUSIONS SRS in older patients for management of Koos grade I or II VS resulted in significantly superior rates of freedom from tumor progression, comparable hearing preservation rates, and significantly higher rates of favorable overall radiographic and neurological outcomes than observation alone. Compared with observation, SRS might be the preferred management option in this patient population.

The NCCN Guidelines for Bladder Cancer provide strategies for the diagnosis, treatment, and follow-up of patients with bladder cancer, which is the sixth most common cancer in the United States. Bladder cancer can be divided into 3 categories along a clinical spectrum: (1) non–muscle-invasive bladder cancer; (2) muscle-invasive bladder cancer; and (3) metastatic bladder cancer, with most patients falling into the category of non–muscle-invasive disease. Thus, the selected content featured in this issue specifically covers the clinical presentation and workup of and subsequent management recommendations for non–muscle-invasive bladder cancer.

OBJECTIVES We aimed to characterize the frequency of major complications of acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C) and adolescents present at 6 months after initial presentation. METHODS The Pediatric Research Immune Network on SARS-CoV-2 and MIS-C (PRISM) study was a prospective cohort at 20 US pediatric academic medical centers. Individuals aged younger than 21 years meeting any of the following were enrolled: SARS-CoV-2 detection within 7 days, Centers for Disease Control and Prevention (CDC) MIS-C criteria, or CDC MIS-C criteria except having involvement of 1 organ system. The study was designed to assess the proportion of children with major complications (cardiovascular, pulmonary, gastrointestinal/hepatic, renal, and/or neurologic) 6 months after presentation. RESULTS Data were analyzed on 229 hospitalized participants: 59 with COVID-19 (mean age 10.4 years; SD, 5.5) and 170 with MIS-C (mean age 10.1 years; SD, 4.8). Overall, 42.8% were female, making up 55.9% and 38.2% of the COVID-19 and MIS-C groups, respectively. Overall, the frequencies of major complications at 6 months after initial presentation were: 16/195 (8.2%) cardiovascular, 11/154 (7.1%) pulmonary, 11/154 (7.1%) gastrointestinal/hepatic, 3/152 (2.0%) renal, and 3/189 (1.6%) neurologic. Organ system complications did not differ significantly between the COVID-19 and MIS-C groups. Six of 14 (42.9%) COVID-19 and 21/26 (80.7%) MIS-C participants with at least 1 six-month complication had no underlying medical condition that may have been associated with their complication(s). CONCLUSIONS Major complications were infrequent but observed in children without underlying medical conditions, underscoring the importance of prospective follow-up to optimize management and elucidate the complications associated with severe SARS-CoV-2 infection in children.

Purpose: The study compares refractive outcomes of secondary intraocular lens (SIOL) surgery performed by vitreoretinal, anterior segment, and both surgeons. Methods: Eyes included in this study underwent SIOL surgery from 2012 to 2024 and had a final postoperative visual acuity of 20/50 or better. Regression analysis compared refractive outcomes, and chi-squared analysis compared complications between subspecialty of SIOL surgeons. Results: A total of 94, 104, and 80 eyes were included in the retina surgeon, anterior segment surgeon, and combo surgeon cohorts, respectively. There was no significant difference in error between target and final postoperative spherical equivalence between retina and combo ( P = 0.079), retina and anterior segment ( P = 0.135), or anterior segment and combo cohorts ( P = 0.567). There was no significant difference in number of eyes with final spherical equivalence within 1 diopter of target spherical equivalence between retina and combo ( P = 0.136), retina and anterior segment ( P = 0.061), or anterior segment and combo cohorts ( P = 0.783). The retina cohort had higher postoperative corneal edema than the combo ( P = 0.017) and the anterior segment cohorts ( P = 0.035). The combo cohort had more postoperative retinal detachment than the anterior segment cohort ( P = 0.046). Conclusion: In eyes with good final vision, retina and anterior segment surgeons have similar refractive outcomes after SIOL surgery.

Abstract Introduction Ultrasonic vaping devices like SURGE are marketed as safer alternatives to conventional coil-based electronic cigarettes like JUUL due to their lower operating temperatures. However, their impact on cardiovascular health has not been fully characterized. Methods Sprague–Dawley rats were exposed daily for 9 weeks to aerosol generated from SURGE, JUUL, or clean air. Heart rate variability was continuously monitored via implanted telemetry. Cardiac fibrosis was quantified using histological analysis. Temperature profiles of SURGE, JUUL, and Nautilus (a coil-based tank device) were recorded. Aerosol samples were analyzed for carbonyl compounds using high-performance liquid chromatography. Results Both SURGE and JUUL exposures significantly reduced heart rate variability (high frequency and total power) compared with air. JUUL exposure significantly increased cardiac fibrosis; SURGE showed a similar mean fibrosis level but greater variability, resulting in a non-significant difference. SURGE devices operated at lower peak temperatures (~131°C) than JUUL (~239°C) and Nautilus (~160–170°C). Despite having the lowest temperature, SURGE emitted higher levels of carbonyl compounds than JUUL, although still substantially lower than Nautilus. Conclusions Although SURGE operates without coils and at lower temperatures than coiled vaping devices, it generates higher levels of carbonyls than some coiled devices and impairs cardiac autonomic regulation, and it can cause cardiac fibrosis comparable with JUUL although with high variability; that is, SURGE does not reliably avoid the increase in fibrosis caused by conventional electronic cigarettes. These findings suggest that non-thermal mechanisms predominate in mediating cardiovascular toxicity associated with ultrasonic vaping, challenging the assumption that coil-free designs are inherently safer. Implications Despite its lower operating temperature and coil-free design, the SURGE ultrasonic vaping device impaired cardiac autonomic function and promoted fibrosis at a mean level comparable to that of JUUL. These findings challenge claims of reduced harm from coil-less vaping technologies and suggest that non-thermal mechanisms may drive toxicity. Regulatory evaluations should consider device emissions and physiological outcomes—not just hardware features. Physicians and policymakers should be aware that coil-less systems may still pose cardiovascular risks, and marketing these devices as inherently safer may mislead users and undermine tobacco harm reduction efforts.

Chylous effusion is a complication most frequently seen in the iatrogenic setting secondary to thoracic surgery or other intervention. Management of this complication includes conservative measures, surgical exploration/ligation, and percutaneous thoracic duct embolization. This case presents a medically complex patient with persistent chylous effusions after thoracoscopic resection of a fluorodeoxyglucose (FDG) and Cu 64 DOTATATE-avid retrocrural lymph node. Initial conventional fluoroscopic lymphangiogram and thoracic duct embolization were unsuccessful. Subsequent magnetic resonance lymphangiography (MRL) more accurately localized the leak which was then marked with computed tomography-guided needle placement before conversion to fluoroscopically guided embolization. This case demonstrates the utility of MRL as a problem-solving tool for localizing hard-to-treat lymphatic leaks. MRL localized embolization is a safe and effective treatment for lymphatic leaks.