Synchronous Primary Early-Stage Non-Small Cell Lung Cancer: Trends in Management and Factors Associated with Improved Survival.

Background: Outcomes after multi-modality curative-intent treatment for patients with synchronous primary early-stage-I non-small cell lung cancer (SPELC) are inadequately understood.

Methods: We performed a retrospective study using the Veterans Health Administration database of patients diagnosed with two stage I SPELC who received treatment with either stereotactic body radiotherapy (SBRT) and/or surgery from 2006-2024. We evaluated utilization of SBRT and surgery as well factors associated with overall survival (OS) and disease-free survival (DFS) via Cox proportional hazard models.

Defensive tolerance drives the reprogramming and dysfunction of infiltrating pathogenic B cells assuring the maintenance of tolerance.

We previously showed that infiltrating cytotoxic immune cells are reprogrammed to regulatory-like/exhausted cells within accepted kidney allografts through a 'defensive tolerance' mechanism. We observed a regulatory B cell (Breg) signature within the accepted kidney. Here we show that despite a Breg phenotype, neither B cell depletion nor the use of μMT recipients which lack B cells, resulted in kidney allograft rejection.

Adherence to Post-Operative Survivorship Quality Metrics in Early-Stage Non-Small Cell Lung Cancer.

Background: Prior studies assessing quality of care among patients undergoing surgery for non-small cell lung cancer (NSCLC) have largely focused on pre- and peri-operative process-based quality measures. We sought to address this knowledge gap by studying the association between post-operative (i.e.

Tolerogenic Lung Allograft Microenvironment Suppresses Pathogenic Tissue Remodeling Following Respiratory Virus Infection in Mice.

Tolerance after lung transplantation is associated with the induction of Foxp3 regulatory T cell-enriched bronchus-associated lymphoid tissue, which suppresses local and systemic alloimmune responses. How this tolerogenic graft environment shapes responses to respiratory viral infections, a known contributor to adverse outcomes after lung transplantation, remains unknown. Using a mouse model of a seasonally circulating parainfluenza virus, we found that acute infection of tolerant lung allografts results in temporary reductions of both bronchus-associated lymphoid tissue size and abundance of graft-resident Foxp3 cells, but doesn't trigger rejection.

Inflammaging in aged tissues drives remodeling of the CD8 T cell compartment.

Aging profoundly reshapes the immune cell landscape, with particularly strong effects on CD8 T cells, including a marked decline in naïve cells and the emergence of age-associated GZMK CD8 T cells (T cells). Although T cells make up a significant fraction of the aged CD8 T cell compartment, the pathway underlying their development remains unknown. In this study, we demonstrate that T cell development is cell-extrinsic and requires antigen exposure within aged non-lymphoid tissues.

Targeting RUNX1 in Macrophages Facilitates Cardiac Recovery.

Despite advances in disease treatment, our understanding of how damaged organs recover and the mechanisms governing this process remain poorly defined. Here, we mapped the transcriptional and regulatory landscape of human cardiac recovery using single cell multiomics. Macrophages emerged as the most reprogrammed cell type.

Cervical heterotopic heart transplantation in mice using a novel suture technique.

Background: Vascularized transplantation models in mice are critical to understand mechanisms that mediate rejection and to develop new therapeutics. Standard abdominal heterotopic heart transplantation techniques employ an suture technique and are the workhouse of transplant immunology research laboratories. Recently, cervical heterotopic heart transplantation in mice has emerged as an alternative due to several advantages but is conventionally performed by suture or cuff techniques in an fashion.

Maintenance of graft tissue-resident Foxp3+ cells is necessary for lung transplant tolerance in mice.

Mechanisms that mediate allograft tolerance differ between organs. We have previously shown that Foxp3+ T cell-enriched bronchus-associated lymphoid tissue (BALT) is induced in tolerant murine lung allografts and that these Foxp3+ cells suppress alloimmune responses locally and systemically. Here, we demonstrated that Foxp3+ cells that reside in tolerant lung allografts differed phenotypically and transcriptionally from those in the periphery and were clonally expanded.

Acute kidney injury triggers hypoxemia by lung intravascular neutrophil retention that reduces capillary blood flow.

Sterile acute kidney injury (AKI) is common in the clinic and frequently associated with unexplained hypoxemia that does not improve with dialysis. AKI induces remote lung inflammation with neutrophil recruitment in mice and humans, but which cellular cues establish neutrophilic inflammation and how it contributes to hypoxemia is not known. Here we report that AKI induced rapid intravascular neutrophil retention in lung alveolar capillaries without extravasation into tissue or alveoli, causing hypoxemia by reducing lung capillary blood flow in the absence of substantial lung interstitial or alveolar edema.

Tissue-resident CCR2 macrophage TREM-1/3 signaling is necessary for monocyte and neutrophil recruitment to injured hearts.

Triggering receptor expressed on myeloid cells 1 (TREM-1) has been shown to amplify inflammatory signals, such as Toll-like receptor signaling, after infection and sterile injury. While previous studies have demonstrated that TREM-1 activation in circulating immune cells promotes injury, the role of TREM-1 signaling in tissue-resident cells in the context of sterile inflammation remains poorly understood. Here, we used a cardiac transplantation model to dissect how Trem1/3 expression on heart-resident cells regulates sterile inflammation.

Bronchus-associated lymphoid tissue in lung transplantation: a facilitator of rejection or regulator of tolerance?

The role of bronchus-associated lymphoid tissue (BALT) in the regulation of immune responses to transplanted lungs remains an area of interest and controversy. Early studies in a rat pulmonary transplant model suggested BALT may accelerate rejection of grafts by inducing a local and systemic inflammatory response. Such observations were corroborated in intrapulmonary tracheal transplant models in the rat.

Developing approaches to incorporate donor-lung computed tomography images into machine learning models to predict severe primary graft dysfunction after lung transplantation.

Primary graft dysfunction (PGD) is a common complication after lung transplantation associated with poor outcomes. Although risk factors have been identified, the complex interactions between clinical variables affecting PGD risk are not well understood, which can complicate decisions about donor-lung acceptance. Previously, we developed a machine learning model to predict grade 3 PGD using donor and recipient electronic health record data, but it lacked granular information from donor-lung computed tomography (CT) scans, which are routinely assessed during offer review.

infection induces intragraft lymphocytotoxicity that triggers lung transplant antibody-mediated rejection.

How pathogens inhibit transplant tolerance remains unclear. Here, we found that infection, but not other common bacterial respiratory infections, increases antibody-mediated rejection (AMR) risk in recipients of lung transplants. To explore this relationship, we performed orthotopic lung transplants in mice, infected recipients with , and observed for the development of AMR.

The Specialized Donor Care Facility Model Improves Operating Room Efficiency.

Background: Organ procurement organizations coordinate organ donation through 2 distinct models of care: the conventional model, in which donors are managed at hospitals where brain death occurs, and the specialized donor care facility (SDCF) model, where brain dead donors are transferred to a freestanding facility. The aim of this study is to compare operating room efficiency for procurements between the SDCF and conventional models of care.

Methods: We performed a prospective analysis of operating room efficiency between thoracic donor procurement operations performed at a SDCF and other organ procurement organizations using the conventional model of care.

Association between patient medications and postoperative outcomes in early-stage non-small cell lung cancer.

Background: Currently, there is no consensus on how to comprehensively assess comorbidities in lung cancer patients in the clinical setting. Prescription medications may be a preferred comorbidity assessment tool and provide a simple mechanism for predicting postoperative outcomes for lung cancer. We examined the relationship between prescription medications and postoperative outcomes for early-stage non-small cell lung cancer (NSCLC).

Hypoxia sensing in resident cardiac macrophages regulates monocyte fate specification following ischemic heart injury.

Myocardial infarction initiates cardiac remodeling and is central to heart failure pathogenesis. Following myocardial ischemia-reperfusion injury, monocytes enter the heart and differentiate into diverse subpopulations of macrophages. Here we show that deletion of Hif1α, a hypoxia response transcription factor, in resident cardiac macrophages led to increased remodeling and overrepresentation of macrophages expressing arginase 1 (Arg1).

Multidimensional profiling of human T cells reveals high CD38 expression, marking recent thymic emigrants and age-related naive T cell remodeling.

Thymic involution is a key factor in human immune aging, leading to reduced thymic output and a decline in recent thymic emigrant (RTE) naive T cells in circulation. Currently, the precise definition of human RTEs and their corresponding cell surface markers lacks clarity. Analysis of single-cell RNA-seq/ATAC-seq data distinguished RTEs by the expression of SOX4, IKZF2, and TOX and CD38 protein, whereby surface CD38 expression universally identified CD8 and CD4 RTEs.

Early-Stage Lung Cancer in the Era of Lung Cancer Screening: Veterans Health Administration Outperforms Other Insurance Models.

Background: Lung cancer screening guidelines were introduced in the United States in 2013, with variable implementation. This study evaluated temporal diagnostic trends in non-small cell lung cancer (NSCLC) diagnosis since the introduction of these guidelines.

Methods: This retrospective cohort analysis used data from the Veterans Administration Corporate Data Warehouse and the National Cancer Database.

Stress-induced eosinophil activation contributes to postoperative morbidity and mortality after lung resection.

Respiratory failure occurs more frequently after thoracic surgery than abdominal surgery. Although the etiology for this complication is frequently attributed to underlying lung disease present in patients undergoing thoracic surgery, this notion is often unfounded because many patients with normal preoperative pulmonary function often require prolonged oxygen supplementation even after minimal resection of lung tissue. Using a murine model of pulmonary resection and peripheral blood samples from patients undergoing resection of the lung or abdominal organs, we demonstrated that lung surgery initiates a proinflammatory loop that results in damage to the remaining lung tissue, noncardiogenic pulmonary edema, hypoxia, and even death.