Publications by authors named "Derek Byers"

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.

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  • A better understanding of chronic lung allograft dysfunction (CLAD) is needed, as it leads to high mortality rates after lung transplants.
  • The study focused on a genetic variation (C3R102G) that enhances complement activation, finding that lung transplant recipients with this variation tend to have poorer outcomes related to CLAD, especially if they develop donor-specific antibodies.
  • In experiments with mice, decreased regulation of the complement system resulted in worse airway damage and increased B cell activity, linking genetic predisposition to complement activation with worse survival outcomes after lung transplantation.
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While most respiratory viral infections resolve with little harm to the host, severe symptoms arise when infection triggers an aberrant inflammatory response that damages lung tissue. Host regulators of virally induced lung inflammation have not been well defined. Here, we show that enrichment for sialylated, but not asialylated immunoglobulin G (IgG), predicted mild influenza disease in humans and was broadly protective against heterologous influenza viruses in a murine challenge model.

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Post-transplant lymphoproliferative disorders (PTLDs) remain a feared complication of transplantation, with significant morbidity and mortality. The oncogenic Epstein-Barr virus (EBV) is a key pathogenic driver in 50%-80% of cases. Numerous prognostic indices, comprising multiple clinical, epidemiological and tumor characteristics, including EBV tumor positivity, do not consistently associate with worse patient survival, suggesting a potential role for EBV genome variants in determining outcome.

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  • Epithelial cells, which help protect our body, need help from stem cells and immune cells to heal when they're hurt, especially after infections like viruses.
  • Researchers found out that special immune cells (called moDCs) help these epithelial stem cells repair and may lead to long-term health issues if not controlled.
  • They discovered a marker called GPNMB in lung cells from people with conditions like long Covid, asthma, and COPD, which might help understand and treat chronic diseases better.
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  • Scientists found a new medicine called NuP-4 that helps repair lung damage caused by viruses.
  • This medicine works by blocking a special protein called MAPK13, which has a big role in making lung cells change and heal after injury.
  • Researchers showed that NuP-4 can keep helping even after stopping the treatment, and it also helps reduce inflammation and make things better in cells from both mice and humans.
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  • There aren't enough donor lungs for people who need them, so a special scoring system called the LUNDON score was created to help figure out which lungs are better for transplantation.
  • Researchers looked at data from brain-dead donors between 2014 and 2020 to see how well this score predicted successful lung recoveries.
  • They found that improving care for low-scoring donors really helped increase the number of usable lungs, and that using the LUNDON score can help get more organs available for transplant.
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Introduction: Many fundamental discoveries have occurred using primary cells from deceased donor lungs. These cells respond differently to injury when there are underlying co-morbidities like diabetes mellitus, hypertension, aging and exposures to cigarette smoke, cocaine and chronic alcohol use. However, the prevalence of these characteristics in donor lungs utilized for research is currently unknown.

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Epithelial barriers are programmed for defense and repair but are also the site of long-term structural remodeling and disease. In general, this paradigm features epithelial stem cells (ESCs) that are called on to regenerate damaged tissues but can also be reprogrammed for detrimental remodeling. Here we identified a Wfdc21-dependent monocyte-derived dendritic cell (moDC) population that functioned as an early sentinel niche for basal ESC reprogramming in mouse models of epithelial injury after respiratory viral infection.

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  • Some living things can repair themselves after getting hurt, especially at skin or barrier areas, but sometimes this repair can lead to long-term problems instead of healing.
  • Researchers are studying MAPK13, a protein that controls how certain stem cells in the lungs behave after an injury, like from a virus.
  • Experiments showed that when MAPK13 is not present, mice heal from infections without turning their lung cells into scar-like tissue, suggesting that controlling MAPK13 might help prevent diseases like asthma and COPD.
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Lung transplantation is the only curative treatment for end-stage lung disease, which is caused by a wide variety of pathologies and encountered in a diverse range of patients. Potential recipients, as well as donors are carefully evaluated by imaging prior to transplant for contraindications to the transplant. After transplantation, recipients are imaged in the immediate, early, intermediate, and late periods for complications that may arise and require intervention.

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Rationale: Recent studies suggest that both hypo- and hyperinflammatory acute respiratory distress syndrome (ARDS) phenotypes characterize severe COVID-19-related pneumonia. The role of lung Severe Acute Respiratory Syndrome - Coronavirus 2 (SARS-CoV-2) viral load in contributing to these phenotypes remains unknown.

Objectives: To redefine COVID-19 ARDS phenotypes when considering quantitative SARS-CoV-2 RT-PCR in the bronchoalveolar lavage of intubated patients.

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Lung transplantation (LTx) continues to have lower rates of long-term graft survival compared with other organs. Additionally, lung utilization rates from brain-dead donors remain substantially lower compared with other solid organs, despite a growing need for LTx and the significant risk of waitlist mortality. This study aims to examine the effects of using a combination of the recently described novel lung donor (LUNDON) acceptability score and the newly adopted recipient lung Composite Allocation Score (CAS) to guide transplantation.

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IL-33 is a cytokine central to type 2 immune pathology in chronic airway disease. This cytokine is abundantly expressed in the respiratory epithelium and increased in disease, but how expression is regulated is undefined. Here we show that increased IL33 expression occurs from multiple noncanonical promoters in human chronic obstructive pulmonary disease (COPD), and it facilitates production of alternatively spliced isoforms in airway cells.

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  • - The lymphatic system in the lungs helps maintain balance by draining fluids and managing immune cells, crucial for responding to lung injuries, particularly in chronic obstructive pulmonary disease (COPD) linked to cigarette smoke exposure.
  • - Research indicates that cigarette smoke and increased thrombin can negatively affect lymphatic endothelial cells (LECs), leading to changes that promote inflammation and hinder normal blood flow and healing processes in COPD.
  • - Findings from cell culture and animal studies reveal that exposure to cigarette smoke extracts reduces important fibrinolytic activity in LECs, elevating inflammatory markers and prothrombotic pathways, highlighting the need for further investigation into LECs’ role in COPD.
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Background: Chronic lung allograft dysfunction (CLAD) is the leading cause of death beyond the first year after lung transplantation. The development of donor-specific antibodies (DSA) is a recognized risk factor for CLAD. Based on experience in kidney transplantation, we hypothesized that belatacept, a selective T-cell costimulatory blocker, would reduce the incidence of DSA after lung transplantation, which may ameliorate the risk of CLAD.

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Common respiratory diseases continue to represent a major public health problem, and much of the morbidity and mortality is due to airway inflammation and mucus production. Previous studies indicated a role for mitogen-activated protein kinase 14 (MAPK14) in this type of disease, but clinical trials are unsuccessful to date. Our previous work identified a related but distinct kinase known as MAPK13 that is activated in respiratory airway diseases and is required for mucus production in human cell-culture models.

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Objectives: There is an increasing appreciation for the need to study mucosal antibody responses in humans. Our aim was to determine the utility of different types of samples from the human respiratory tract, specifically nasopharyngeal (NP) swabs obtained for diagnostic purposes and bronchoalveolar lavage (BAL) obtained in outpatient and inpatient settings.

Methods: We analysed antibody levels in plasma and NP swabs from 67 individuals with acute influenza as well as plasma and BAL from individuals undergoing bronchoscopy, including five control subjects as well as seven moderately and seven severely ill subjects with a respiratory viral infection.

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  • Primary graft dysfunction (PGD) is a major cause of complications after lung transplant, occurring in 30% of patients in this study.
  • This research used machine learning to predict PGD grade 3 within 72 hours post-transplant by analyzing donor and recipient data known at the time of donor offer acceptance.
  • The final predictive model showed moderate accuracy (AUC of 0.65) and could potentially enhance matching and utilization of donors in lung transplantation.
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  • Common respiratory diseases cause significant public health issues due to airway inflammation and excessive mucus production, driven by certain kinases, particularly MAPK14 and MAPK13.
  • Previous studies showed MAPK13's essential role in mucus production, yet early inhibitor drugs weren't fully optimized or tested in living models.
  • The study introduces NuP-3, a new and more effective inhibitor targeting MAPK13-14, which successfully reduces mucus production and inflammation in human cell cultures and minipig models of airway disease.
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  • Tocilizumab (TCZ) is an IL-6 inhibitor that has shown effectiveness in treating donor-specific antibodies (DSA) and chronic antibody-mediated rejection (AMR) in kidney transplant patients, but its application in lung transplants was previously unexplored.
  • A study compared 9 lung transplant patients treated with TCZ for AMR to 18 patients treated without TCZ, finding that TCZ led to better DSA clearance, reduced DSA recurrence, and lower graft failure rates.
  • The side effects such as infusion reactions and infections were similar in both groups, indicating the potential for TCZ in treating pulmonary AMR and supporting further research into randomized controlled trials for IL-6 inhibitors.
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Background: Appropriate size matching between donor and recipient is critical for successful pulmonary transplantation. Although surrogate measurements such as height and gender are often utilized to approximate predicted lung volume, these methods provide only a gross estimation with wide variability and poor predictive value.

Case Description: A single center exploratory study was conducted in which four patients underwent lung transplantation (LT) with pre-operative computed tomography (CT) volumetry obtained in both the donor and recipient to facilitate decision making regarding organ size and suitability.

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Objective: National and institutional data suggest an increase in organ discard rate (donor lungs procured but not implanted) after a new lung allocation policy was introduced in 2017. However, this measure does not include on-site decline rate (donor lungs declined intraoperatively). The objective of this study is to examine the impact of the allocation policy change on on-site decline.

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Background: Accumulated knowledge on the outcomes related to size mismatch in lung transplantation derives from predicted total lung capacity equations rather than individualized measurements of donors and recipients. The increasing availability of computed tomography (CT) makes it possible to measure the lung volumes of donors and recipients before transplantation. We hypothesize that CT-derived lung volumes predict a need for surgical graft reduction and primary graft dysfunction.

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