Yifan Wang

Sotatercept, a first‐in‐class activin signaling inhibitor, improves pulmonary vascular hemodynamics and clinical outcomes in pulmonary arterial hypertension (PAH). However, despite reductions in mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR), cardiac output (CO) does not generally increase, and some patients experience a decline in CO, a finding of unclear clinical significance. We sought to characterize the heterogeneity of CO responses to sotatercept in PAH and to determine whether incorporating oxygen delivery (DO ₂ ) provides additional insight into the physiological significance of these changes. We retrospectively analyzed PAH patients who underwent right heart catheterization before and during sotatercept therapy (median 7.3 months, IQR 4.8, 9.3). Hemodynamic, echocardiographic, hematologic, and clinical parameters were collected, including functional class, 6‐min walk distance (6MWD) and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP). Patients were dichotomized by CO response (decreased vs. maintained), and DO ₂ was calculated at each catheterization. A total of 56 patients were included. While most demonstrated reductions in PVR and mPAP, 63% experienced decreased CO. Improvements in 6MWD and NT‐proBNP were similar between groups, and hemoglobin increased comparably. However, among patients with decreased CO, 63% had a concomitant decline in DO ₂ accompanied by worsening 6MWD and a reduced NT‐proBNP response. In this real‐world cohort, over half of sotatercept‐treated PAH patients experienced reduced CO despite overall hemodynamic and clinical improvement. Concomitant reductions in DO ₂ identify a subgroup with worse functional outcomes. These findings suggest that DO ₂ adds additional information beyond CO alone when assessing the physiological response to sotatercept.

Background: Non-occupational exposures are increasingly recognized as a driver of poor outcomes in patients with interstitial lung disease (ILD), including urban and rural populations. However, both populations also experience barriers to care and higher social vulnerability that may be associated with higher risk for progression. The impact of agricultural antigen exposure and concomitant social vulnerability has not been well characterized. Objectives: To evaluate the risk of progression in both urban and agricultural antigen-exposed communities in patients with ILD. Design: Retrospective cohort study. Methods: We identified individuals with a diagnosis of ILD in a large health system. Proximity to agricultural antigens was mapped utilizing satellite-derived crop data. Residence in a community impacted by structural disadvantage was estimated using the social vulnerability index (SVI). We used geographically weighted regression analysis to estimate the risk of progression, defined as a greater than 10% relative decrease in forced vital capacity within the 24 months from first documented diagnosis. Results: Residence in a high SVI community was associated with an increased risk of disease progression by FVC criteria in both agriculturally exposed and urban communities. The greatest risk of progression was seen in those residing in high SVI, rural communities (HR 1.19, CI: 1.09–1.31). Conclusion: Within a large cohort of geographically diverse patients with ILD, residential social vulnerability increased the risk of ILD progression with effects similar in individuals with agricultural antigen exposure and urban exposures.

Background: Among patients who are invasively ventilated in the hospital, 5–9% undergo tracheostomy for prolonged support. The preferred method of in-hospital mechanical ventilation weaning and liberation strategy for patients with tracheostomy is not well-established. Methods: A team of respiratory therapists and physicians at the Cleveland Clinic Main Campus Hospital implemented a ventilator liberation protocol for patients with tracheostomy that incorporated daily tracheostomy collar trials. We compared clinical outcomes during the first year of protocol implementation with the year prior. All patients with tracheostomy, including those who had an existing tracheostomy on admission and those who had a tracheostomy performed in the ICU, were included. Results: There were 308 unique subjects accounting for 386 ICU admissions. The primary analysis included the first mechanical ventilation episode of each hospital admission (185 in control, and 201 in intervention). Baseline characteristics were similar between the groups. At admission, 251 subjects (65%) had an existing tracheostomy; the rest (135 subjects, 35%) underwent tracheostomy after admission. Median APACHE score (IQR) was 74 (59–95) and was not significantly different between groups. Weaning duration (IQR) was 5.6 (2.2–13.0) days in the intervention group and 7.0 (2.6–11.7) days in the control group ( P = .50). The hospital stay and mortality were similar. More subjects were readmitted to the hospital in the intervention group (30.3%) compared with control (20%) ( P = .02). Considering the first mechanical ventilation episode and after adjusting for age, gender, APACHE III diagnosis and APACHE III score, the intervention group showed a trend of higher likelihood of ventilator liberation on hospital discharge compared with control group (HR = 1.29, 95% CI 0.98–1.71, P = .07). For recurrent events (up to 3), tracheostomy collar trials were associated with a 43% higher likelihood of successful liberation (HR 1.43, 95% CI 1.05–1.94, P = .02). Among subjects who underwent tracheostomy during the ICU admission, the daily tracheostomy trials were associated with an increased hazard of ventilator liberation on discharge (HR = 1.58, 95% CI 0.97–2.57, P = .08), after adjustment for confounders. Conclusions: Tracheostomy collar trials were associated with an increase in-hospital ventilator liberation for subjects with tracheostomy with the balancing measure of increase in hospital readmissions. The benefits were pronounced for subjects who had tracheostomy during the ICU admission.

Background Identifying the cause of interstitial lung disease (ILD) remains difficult. While surgical lung biopsy remains the gold standard, transbronchial lung cryobiopsy (TBLC) represents a minimally invasive alternative with an improved safety profile and acceptable diagnostic accuracy. Real time imaging with cone beam computed tomography (CBCT) guidance may improve TBLC, but data supporting this approach remains limited. We analyzed the safety profile of performing TBLC with mobile CBCT guidance and compared it to historical controls using other modalities. Methods We performed a retrospective, single center analysis of patients undergoing TBLC with mobile CBCT from June 2023 through July 2025 for ILD evaluation. The primary study end point was safety, defined as pneumothorax or pulmonary hemorrhage incidence. Radiation dose, ILD diagnosis, and change in patient management were secondary endpoints. Results 128 patients underwent TBLC with mobile CBCT. No complications occurred after TBLC. After transbronchial forceps biopsy, however, pneumothorax occurred in two patients, without the need for tube thoracostomy. Grade 2 bleeding occurred in one patient. Mean radiation exposure was 157±77mGy, which was less compared to fixed CBCT guidance (1171±309mGy) and comparable to 2D fluoroscopy (110±78mGy). 89% (114/128) of patients received a final diagnosis of a specific ILD, with 68% (87/128) starting at least one new medication. Conclusion TBLC with mobile CBCT guidance is safe and effective in facilitating diagnoses and management changes in ILD patients. Radiation exposure is decreased compared to fixed CBCT and comparable to 2D fluoroscopic guidance.

Introduction: Lung cancer is a leading cause of cancer-related deaths globally, with approximately 1.5 million new peripheral pulmonary lesions (PPLs) detected annually in the United States. Robotic-assisted bronchoscopy (RAB) has emerged as a promising technology, with two platforms initially approved, the Monarch platform (Auris Health Inc, Redwood City, CA, USA) and the Ion Endoluminal System (Intuitive Surgical, Sunnyvale, CA, USA), offering improved stability and distal airway visualization. As RAB adoption increases, there is a critical need for comparative effectiveness data of these systems to guide clinical decision-making and institutional investments. This study aims to compare the diagnostic yield and safety profiles of the Ion and Monarch RAB platforms after introduction at a single institution. Methods: We conducted a retrospective chart review of patients undergoing RAB in the first six months following the introduction of each platform. Demographic and radiographic data were collected. Diagnostic yield was defined as obtaining a malignant or specific benign diagnosis from bronchoscopy. Results: The study included 56 Ion and 36 Monarch procedures. Diagnostic yield was similar between Ion (75%) and Monarch (72%) groups (p = 0.8), with an adjusted odds ratio 0.89 (95% CI 0.30–2.72). Complications were low, with one pneumothorax occurring in each group. Conclusions: Early adoption and use of both RAB platforms suggests comparable diagnostic yields and safety profiles in our limited sample size. Larger studies including standardized anesthesia protocol and systematic use of real-time imaging are needed for further evaluation and comparative analysis.

Background: Measurement error in imaging reduces statistical power and potentially biases parameter estimation, compromising study reliability. Purpose: To introduce a dual data collection design (reliability and main datasets) to quantify measurement error and apply regression calibration to correct error‐prone imaging markers, thereby improving biomarker‐outcome estimation, statistical power, and sample size planning. Study Type: Prospective (reliability) and retrospective (regression calibration). Population: 65 healthy volunteers (mean age: 23.2), 60 age and sex matched with 34 epilepsy patients (mean age: 28.7). Field Strength/Sequence: 3.0 T, MR fingerprinting (MRF) and T1‐weighted (T1w) MPRAGE. Assessment: Three‐dimensional brain scan‐rescan data were acquired in 5 volunteers (6 identical acquisitions per volunteer across 3 scanners) to estimate reliability coefficients () for MRF T1 and T1w signal intensity (SI) mean and standard deviation (SD). These coefficients were applied in regression calibration to correct imaging markers in the epilepsy cohort. Effect sizes for distinguishing lesional from control were compared before and after correction. Simulations evaluated the impact of additive and proportional bias on sample size, statistical power, and association estimates under single and multi‐scanner scenarios. Statistical Test: Reliability coefficient, Cohen's d , regression calibration, generalized estimation equations. Results: MRF T1 markers exhibited higher reliability ( = 0.887–0.941) than T1w SI markers with site effects ( = 0.246–0.554). Regression calibration increased effect size more for T1w SI mean (333.22% increase) than for MRF T1 mean (12.57% increase). In multi‐site simulations, regression calibration alone achieved unbiased estimate under small site effects (additive and proportional SD ≤ 0.2), whereas under larger site effects (additive SD ≥ 0.5) only the combined regression calibration and Combat produced near‐zero bias (−0.024), outperforming naïve analysis (−0.423). Data Conclusion: The dual data acquisition design with regression calibration restores attenuated imaging biomarker associations, improves statistical power, and informs sampling requirements, thus enhancing reliability and generalizability in multi‐site imaging studies. Evidence Level: 3. Technical Efficacy: 2.

Background: Immunocompromised patients, especially those receiving B–cell–depleting therapy (BCDT), remain at high risk for severe coronavirus disease 2019 (COVID–19). Although monoclonal antibodies showed benefit pre–Omicron, the real–world effectiveness of the oral antivirals in BCDT recipients is unclear. Methods: We emulated a target trial using the Cleveland Clinic electronic health record. Adult patients (≥18 years) with immune–mediated inflammatory diseases who received rituximab or ocrelizumab and tested positive for severe acute respiratory syndrome coronavirus 2 between 19 December 2021 and 30 June 2025 were eligible. The primary endpoint was hospitalization or death within 21 days; the secondary endpoint was death within 90 days. Propensity scores adjusted for confounding, and Weighted Cox regression models were used to evaluated treatment effects. Results: Among 255 853 COVID–19 cases, 876 met criteria for the nirmatrelvir/ritonavir cohort (411 treated, 465 untreated) and 566 for the molnupiravir cohort (91 treated, 475 untreated). In the nirmatrelvir/ritonavir cohort, 18 (4.4%) of treated versus 43 (9.2%) of untreated patients were hospitalized or died within 21 days. After weighting, nirmatrelvir/ritonavir reduced the hazard by 44% (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.31–0.99). In the molnupiravir cohort, 6 (6.6%) of treated and 46 (9.7%) of untreated patients met the primary endpoint; the weighted HR was 0.56 (95% CI, 0.24–1.33), not statistically significant. Conclusions: Early outpatient nirmatrelvir/ritonavir significantly lowers the risk of COVID–19–related hospitalization or death in patients on BCDT. Molnupiravir showed a nonsignificant trend toward benefit. These findings support prioritizing nirmatrelvir/ritonavir for high–risk immunocompromised populations.