Trastuzumab Deruxtecan Combination Strongly Enhances Responses and Overcomes Sotorasib Resistance in -Mutant NSCLC.

Introduction: Recent advances in the treatment of -mutant non-small cell lung cancer (NSCLC) have led to the development of KRAS inhibitors, such as sotorasib and adagrasib. However, resistance and disease progression remain significant challenges. In this study, we investigated the therapeutic potential of combining trastuzumab deruxtecan (T-DXd), an anti-HER2 antibody-drug conjugate, with sotorasib in -mutant NSCLC, while also evaluating HER2 expression in NSCLC samples.

Modulation of tissue resident memory T cells by glucocorticoids after acute cellular rejection in lung transplantation.

Acute cellular rejection is common after lung transplantation and is associated with an increased risk of early chronic rejection. We present combined single-cell RNA and TCR sequencing on recipient-derived T cells obtained from the bronchoalveolar lavage of three lung transplant recipients with rejection and compare them with T cells obtained from the same patients after treatment of rejection with high-dose systemic glucocorticoids. At the time of rejection, we found an oligoclonal expansion of cytotoxic CD8+ T cells that all persisted as tissue resident memory T cells after successful treatment.

The Development and Implementation of an Autopsy/ Tissue Donation for Breast Cancer Research.

There is growing interest in tissue procurement for cancer research through autopsy. Establishing an autopsy/tissue donation programme for breast cancer research within an academic medical centre in the United States requires consideration, planning, multi-departmental collaboration and labour-intensive maintenance. It is the purpose of this paper to outline the necessary considerations in implementing and maintaining a tissue donation and autopsy programme within a breast cancer centre at a comprehensive cancer centre.

Machine learning implicates the IL-18 signaling axis in severe asthma.

Asthma is a common disease with profoundly variable natural history and patient morbidity. Heterogeneity has long been appreciated, and much work has focused on identifying subgroups of patients with similar pathobiological underpinnings. Previous studies of the Severe Asthma Research Program (SARP) cohort linked gene expression changes to specific clinical and physiologic characteristics.

Erdheim-Chester Disease: A Case of Right Atrial Involvement and Superior Vena Cava Stenosis.

We describe the case of a 79-year-old woman with a history of Erdheim-Chester disease who presented with bradyarrhythmia and infiltration of the superior vena cava and right atrium. This case highlights an important consideration in type of pacemaker placement given the frequency of right atrial involvement in Erdheim-Chester disease. ().

Disparate Interferon Signaling and Shared Aberrant Basaloid Cells in Single-Cell Profiling of Idiopathic Pulmonary Fibrosis and Systemic Sclerosis-Associated Interstitial Lung Disease.

Idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated interstitial lung disease (SSc-ILD) differ in the predominant demographics and identified genetic risk alleles of effected patients, however both diseases frequently progress to respiratory failure and death. Contrasting advanced SSc-ILD to IPF provides insight to the role dysregulated immunity may play in pulmonary fibrosis. To analyze cell-type specific transcriptome commonalities and differences between IPF and SSc-ILD, we compared single-cell RNA-sequencing (scRNA-seq) of 21 explanted lung tissue specimens from patients with advanced IPF, SSc-ILD, and organ donor controls.

Single cell RNA sequencing identifies IGFBP5 and QKI as ciliated epithelial cell genes associated with severe COPD.

Background: Whole lung tissue transcriptomic profiling studies in chronic obstructive pulmonary disease (COPD) have led to the identification of several genes associated with the severity of airflow limitation and/or the presence of emphysema, however, the cell types driving these gene expression signatures remain unidentified.

Methods: To determine cell specific transcriptomic changes in severe COPD, we conducted single-cell RNA sequencing (scRNA seq) on n = 29,961 cells from the peripheral lung parenchymal tissue of nonsmoking subjects without underlying lung disease (n = 3) and patients with severe COPD (n = 3). The cell type composition and cell specific gene expression signature was assessed.

Pulmonary carcinomas arising in association with scar: Cytomorphologic features in histologically confirmed cases.

Background: Lung carcinoma arising in association with scar tissue is a well-reported but much debated phenomenon. Scar tissue complicates imaging and pathologic tumor measurement for cancer staging. To the best of our knowledge, the cytological findings in lung scar carcinoma (LSC) have not been described in the literature.

Digital Imaging Analysis Reveals Reduced Alveolar α-Smooth Muscle Actin Expression in Severe Asthma.

Expansion of α-smooth muscle actin (α-SMA)-expressing airway smooth muscle of the large airways in asthma is well-studied. However, the contribution of α-SMA-expressing cells in the more distal alveolated parenchyma, including pericytes and myofibroblasts within the alveolar septum, to asthma pathophysiology remains relatively unexplored. The objective of this study was to evaluate α-SMA expression in the alveolated parenchyma of individuals with severe asthma (SA), compared with healthy controls or individuals with chronic obstructive pulmonary disease.

Human ex vivo lung perfusion: a novel model to study human lung diseases.

Experimental animal models to predict physiological responses to injury and stress in humans have inherent limitations. Therefore, the development of preclinical human models is of paramount importance. Ex vivo lung perfusion (EVLP) has typically been used to recondition donor lungs before transplantation.

In-vivo efficacy of biodegradable ultrahigh ductility Mg-Li-Zn alloy tracheal stents for pediatric airway obstruction.

Pediatric laryngotracheal stenosis is a complex congenital or acquired airway injury that may manifest into a potentially life-threatening airway emergency condition. Depending on the severity of obstruction, treatment often requires a combination of endoscopic techniques, open surgical repair, intraluminal stenting, or tracheostomy. A balloon expandable biodegradable airway stent maintaining patency while safely degrading over time may address the complications and morbidity issues of existing treatments providing a less invasive and more effective management technique.

Prognostic significance of microscopic size in peripherally located scar-associated clinical stage I lung carcinomas.

Objectives: Staging of non-small cell lung carcinoma associated with scar is not discussed in detail in the current American Joint Committee on Cancer staging manual. The recommendation is to include the scar area in the tumor size measurement unless the tumor represents a small focus at the edge of the scar. The aim of this study is to investigate if subtraction of the size of the central scar from the total gross size of surgically resected peripheral clinical stage I non-small cell lung carcinoma improves patient stratification into more accurate prognostic groups.

Castleman Disease Presenting with Pseudotumour Cerebri and Myasthenia Gravis: A Case Report and Literature Review.

Castleman disease (CD) is a rare lymphoproliferative disorder that may present with various autoimmune, inflammatory, or neurologic syndromes. This is a case of a 21-year-old woman who presented with signs and symptoms of pseudotumour cerebri (PTC) who subsequently developed myasthenia gravis (MG), and was incidentally found to have a large mass in the posterior mediastinum. Upon resection, the mass was classified as unicentric CD involved with follicular dendritic cell sarcoma.

Co-existence of vocal cord dysfunction with pulmonary conditions other than asthma: A case series.

Background: Vocal cord dysfunction (VCD) is defined as inappropriate movement of the vocal cords resulting in functional airway obstruction and symptoms including cough, wheezing, and dyspnea. VCD is often misdiagnosed with asthma but can also co-exist with asthma. The association of VCD with other serious pulmonary conditions has not been described to date.

Whole-exome sequencing identifies unique mutations and copy number losses in calcifying fibrous tumor of the pleura: report of 3 cases and review of the literature.

Calcifying fibrous tumor of the pleura (CFTP) is a rare mesenchymal tumor of unknown pathogenesis. The diagnosis often requires exclusion of other common entities. Our aim was to determine if genomic changes were associated with CFTP that could contribute to mechanisms underlying tumorigenesis.

An online readability analysis of pathology-related patient education articles: an opportunity for pathologists to educate patients.

Information for patients regarding their clinical conditions and treatment options is widely available online. The American Medical Association and National Institutes of Health recommend that online patient-oriented materials be written at no higher than a seventh-grade reading level to ensure full comprehension by the average American. This study sought to determine whether online patient-oriented materials explaining common pathology procedures are written at appropriate reading levels.

A comparison of ALK gene rearrangement and ALK protein expression in primary lung carcinoma and matched metastasis.

Aims: The 2013 College of American Pathologists, the Association for Molecular Pathology and the International Association for the Study of Lung Cancer guideline for EGFR and ALK testing in lung carcinoma indicates that either the primary tumour or the metastasis is suitable for testing. The heterogeneity of gene mutations has been studied extensively, while similar reports on gene rearrangements are limited. The aim of this study was to determine if ALK status between primary tumour and matched metastasis differs.

Sex steroid receptor expression in idiopathic pulmonary fibrosis.

Usual interstitial pneumonia (UIP) is characterized by progressive scarring of the lungs and is associated with high morbidity and mortality despite therapeutic interventions. Sex steroid receptors have been demonstrated to play an important role in chronic lung conditions; however, their significance is unknown in patients with UIP. We retrospectively reviewed 40 idiopathic UIP cases for the expression of hormonal receptors.

Histologic Findings of Severe/Therapy-Resistant Asthma From Video-assisted Thoracoscopic Surgery Biopsies.

The histologic changes occurring in severe/therapy-resistant asthma (SA) as defined by the European Respiratory Society/American Thoracic Society guidelines, particularly at the level of the distal airways are unknown. This study describes the clinical, radiologic, and histologic characteristics of 29 SA patients who underwent video-assisted thoracoscopic surgery lung biopsy. Pathologic observations were correlated with clinical features, especially the presence of autoimmune disease (AID) (15/29, 51.

Pulmonary Alveolar Microlithiasis: AIRP Best Cases in Radiologic-Pathologic Correlation.

Editor's Note.-RadioGraphics continues to publish radiologic-pathologic case material selected from the American Institute for Radiologic Pathology (AIRP) "best case" presentations. The AIRP conducts a 4-week Radiologic Pathology Correlation Course, which is offered five times per year.

Granulomatosis with Polyangiitis Presenting with Coronary Artery and Pericardial Involvement.

Granulomatosis with polyangiitis is a systemic disease resulting in necrotizing vasculitis of small- and medium-sized vessels. Cardiac involvement is rare and when present usually manifests with pericarditis and coronary artery vasculitis. We report here a case of granulomatosis with polyangiitis involving the native coronary arteries, bypass graft, and pericardium with interesting imaging findings on contrast-enhanced CT and MRI.

Focused Screening Identifies Evoxine as a Small Molecule That Counteracts CO2-Induced Immune Suppression.

Patients with severe lung disease may develop hypercapnia, elevation of the levels of CO2 in the lungs and blood, which is associated with increased risk of death, often from infection. To identify compounds that ameliorate the adverse effects of hypercapnia, we performed a focused screen of 8832 compounds using a CO2-responsive luciferase reporter in Drosophila S2* cells. We found that evoxine, a plant alkaloid, counteracts the CO2-induced transcriptional suppression of antimicrobial peptides in S2* cells.

Sensitive Detection of Mono- and Polyclonal ESR1 Mutations in Primary Tumors, Metastatic Lesions, and Cell-Free DNA of Breast Cancer Patients.

Purpose: Given the clinical relevance of ESR1 mutations as potential drivers of resistance to endocrine therapy, this study used sensitive detection methods to determine the frequency of ESR1 mutations in primary and metastatic breast cancer, and in cell-free DNA (cfDNA).

Experimental Design: Six ESR1 mutations (K303R, S463P, Y537C, Y537N, Y537S, D538G) were assessed by digital droplet PCR (ddPCR), with lower limits of detection of 0.05% to 0.

High CO2 Leads to Na,K-ATPase Endocytosis via c-Jun Amino-Terminal Kinase-Induced LMO7b Phosphorylation.

The c-Jun amino-terminal kinase (JNK) plays a role in inflammation, proliferation, apoptosis, and cell adhesion and cell migration by phosphorylating paxillin and β-catenin. JNK phosphorylation downstream of AMP-activated protein kinase (AMPK) activation is required for high CO2 (hypercapnia)-induced Na,K-ATPase endocytosis in alveolar epithelial cells. Here, we provide evidence that during hypercapnia, JNK promotes the phosphorylation of LMO7b, a scaffolding protein, in vitro and in intact cells.