Anterior bridging bronchus

Previously reported patients with a bridging bronchus (BB) presented with respiratory distress. In addition, each patient had one or more associated anomalies. All but two patients progressed to cardiopulmonary failure and death. We describe a case of an anterior BB without associated anomalies, who did well without operative intervention. This patient presented with a cough at 6 months of age. Chest X-ray was normal, but due to suspicion of foreign body aspiration, bronchoscopy was performed, which revealed a third bronchus at the carina. Bronchography demonstrated the anatomy of the BB. The patient has continued to do well without further intervention. Pediatr Pulmonol. 2003; 35:70–72. © 2003 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35321/1/10205_ftp.pd

Abstract P23: RHOA inactivation subverts IFN-γ response and promotes antigen escape in CAR-T resistant diffuse large B-cell lymphoma

Abstract CD19-directed chimeric antigen receptor T-cell (CAR-T) therapies have shown breakthrough responses for relapsed or refractory diffuse large B-cell lymphoma (DLBCL), however, over half of patients still progress. Whole genome sequencing of CAR-T treated patients revealed RHOA (3p21.31) deletions highly enriched in patients with poor responses (p = 0.0013). RHOA is altered in approximately 25% of newly diagnosed DLBCL, yet no work has comprehensively defined its role in lymphoma biology or immune resistance. We created RHOA loss-of-function (LoF) cell lines and performed RNA-sequencing followed by drug viability assays to interrogate pathways of dependence in RHOA deficient DLBCL. We also created immunocompetent models of RHOA deficient lymphoma in vivo and conducted single-cell RNA sequencing to assess the resulting lymphoma microenvironments. CAR-T cells were engineered and used to challenge RHOA LoF tumors in vitro. Upon discovering highly upregulated gene sets involving PI3K/AKT/mTOR signaling, we employed drug viability assays and established a critical reliance on AKT signaling in RHOA LoF cell lines. Upregulated AKT was found to suppress JAK2-STAT1 mediated (IFN-γ) signaling and this effect was reversed with PI3K inhibition. Single-cell transcriptomics of RHOA deficient mouse lymphomas revealed decreased Cd8a expression and increased Cd4 expression of T-cells (p = 0.09 and p = 0.028, respectively), suggesting an immunosuppressive microenvironment as a result of abolished IFN-γ mediated immunorecognition. RHOA deficient cell lines were also found to downregulate surface CD19 expression (p < 0.0001) and demonstrated significantly decreased CAR-T cell killing in vitro (p = 0.0005). Future experiments will challenge RHOA deficient immunocompetent tumors in vivo with and without PI3K inhibitors to assess efficacy of combinatorial therapy. Citation Format: Austin D Newsam, Caroline A Coughlin, Yitzhar E Goretsky, Abdessumad Y Alaoui, Daniel E Tsai, David G Coffey, Anya K Sondhi, Evan R Roberts, Natalia Campos Gallego, Paola Manara, Daniel Bilbao, Bachisio Ziccheddu, Jay Y Spiegel, Michael D Jain, Frederick L Locke, Juan P Alderuccio, Francesco Maura, Jonathan H Schatz. RHOA inactivation subverts IFN-γ response and promotes antigen escape in CAR-T resistant diffuse large B-cell lymphoma [abstract]. In: Proceedings of the Blood Cancer Discovery Symposium; 2024 Mar 4-6; Boston, MA. Philadelphia (PA): AACR; Blood Cancer Discov 2024;5(2_Suppl):Abstract nr P23

Prospective Multicenter Study of Surgical Correction of Pectus Excavatum: Design, Perioperative Complications, Pain, and Baseline Pulmonary Function Facilitated by Internet-Based Data Collection

Background: Given widespread adoption of the Nuss procedure, prospective multicenter study of management of pectus excavatum by both the open and Nuss procedures was thought desirable. Although surgical repair has been performed for more than 50 years, there are no prospective multicenter studies of its management. Study Design: This observational study followed pectus excavatum patients treated surgically at 11 centers in North America, according to the method of choice of the patient and surgeon. Before operation, all underwent evaluation with CT scan, pulmonary function tests, and body image survey. Data were collected about associated conditions, hospital complications, and perioperative pain. One year after completion of treatment, patients will repeat the preoperative evaluations. This article addresses early results only. Results: Of 416 patients screened, 327 were enrolled; 284 underwent the Nuss procedure and 43 had the open procedure. Median preoperative CT index was 4.4. Pulmonary function testing before operation showed mean forced vital capacity of 90% of predicted values; forced expiratory volume in 1 second (FEV1), 89% of predicted; and forced expiratory flow during the middle half of the forced vital capacity (FEF25% to 75%), 85% of predicted. Early postcorrection results showed that operations were performed without mortality and with minimal morbidity at 30 days postoperatively. Median hospital stay was 4 days. Postoperative pain was a median of 3 on a scale of 10 at time of discharge; the worst pain experienced was the same as was expected by the patients (median 8), and by 30 days after correction or operation, the median pain score was 1. Because of disproportionate enrollment and similar early complication rates, statistical comparison between operation types was limited. Conclusions: Anatomically severe pectus excavatum is associated with abnormal pulmonary function. Initial operative correction performed at a variety of centers can be completed safely. Perioperative pain is successfully managed by current techniques

Multicenter study of pectus excavatum, final report: complications, static/exercise pulmonary function, and anatomic outcomes.

BackgroundA multicenter study of pectus excavatum was described previously. This report presents our final results.Study designPatients treated surgically at 11 centers were followed prospectively. Each underwent a preoperative evaluation with CT scan, pulmonary function tests, and body image survey. Data were collected about associated conditions, complications, and perioperative pain. One year after treatment, patients underwent repeat chest CT scan, pulmonary function tests, and body image survey. A subset of 50 underwent exercise pulmonary function testing.ResultsOf 327 patients, 284 underwent Nuss procedure and 43 underwent open procedure without mortality. Of 182 patients with complete follow-up (56%), 18% had late complications, similarly distributed, including substernal bar displacement in 7% and wound infection in 2%. Mean initial CT scan index of 4.4 improved to 3.0 post operation (severe &gt;3.2, normal = 2.5). Computed tomography index improved at the deepest point (xiphoid) and also upper and middle sternum. Pulmonary function tests improved (forced vital capacity from 88% to 93%, forced expiratory volume in 1 second from 87% to 90%, and total lung capacity from 94% to 100% of predicted (p &lt; 0.001 for each). VO2 max during peak exercise increased by 10.1% (p = 0.015) and O2 pulse by 19% (p = 0.007) in 20 subjects who completed both pre- and postoperative exercise tests.ConclusionsThere is significant improvement in lung function at rest and in VO2 max and O2 pulse after surgical correction of pectus excavatum, with CT index &gt;3.2. Operative correction significantly reduces CT index and markedly improves the shape of the entire chest, and can be performed safely in a variety of centers

Increasing Severity of Pectus Excavatum Is Associated with Reduced Pulmonary Function

Objective To determine whether pulmonary function decreases as a function of severity of pectus excavatum, and whether reduced function is restrictive or obstructive in nature in a large multicenter study. Study design We evaluated preoperative spirometry data in 310 patients and lung volumes in 218 patients aged 6 to 21 years at 11 North American centers. We modeled the impact of the severity of deformity (based on the Haller index) on pulmonary function. Results The percentages of patients with abnormal forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), forced expiratory flow from 25% exhalation to 75% exhalation, and total lung capacity findings increased with increasing Haller index score. Less than 2% of patients demonstrated an obstructive pattern (FEV1/FVC \u3c67%), and 14.5% demonstrated a restrictive pattern (FVC and FEV1 \u3c80% predicted; FEV1/FVC \u3e80%). Patients with a Haller index of 7 are \u3e4 times more likely to have an FVC of ≤80% than those with a Haller index of 4, and are also 4 times more likely to exhibit a restrictive pulmonary pattern. Conclusions Among patients presenting for surgical repair of pectus excavatum, those with more severe deformities have a much higher likelihood of decreased pulmonary function with a restrictive pulmonary pattern