Candidemia in thoracic solid organ transplant recipients: Characteristics and outcomes relative to matched uninfected and bacteremic thoracic organ transplant recipients.

Background: Little is understood about the risk factors and outcomes from candidemia in thoracic solid organ transplant recipients.

Methods: This is a single-center retrospective cohort study of patients undergoing heart or lung transplant between January 1, 2013 and December 31, 2022. We performed two comparisons among heart and lung transplant recipients: (1) recipients with candidemia versus matched, uninfected recipients, and (2) recipients with candidemia versus recipients with bacteremia.

Study on the relationship between selenium and cadmium in diseased human lungs.

Cadmium (Cd) is a toxic environmental metal that interacts with selenium (Se) and contributes to many lung diseases. Humans have widespread exposures to Cd through diet and cigarette smoking, and studies in rodent models show that Se can protect against Cd toxicities. We sought to identify whether an antagonistic relationship existed between Se and Cd burdens and determine whether this relationship may associate with metabolic variation within human lungs.

A scalable workflow to characterize the human exposome.

Complementing the genome with an understanding of the human exposome is an important challenge for contemporary science and technology. Tens of thousands of chemicals are used in commerce, yet cost for targeted environmental chemical analysis limits surveillance to a few hundred known hazards. To overcome limitations which prevent scaling to thousands of chemicals, we develop a single-step express liquid extraction and gas chromatography high-resolution mass spectrometry analysis to operationalize the human exposome.

Frailty in Lung Transplantation: Candidate Assessment and Optimization.

The concept of frailty has gained considerable interest in clinical solid-organ transplantation over the past decade. Frailty as a phenotypic construct to describe a patient's risk from biologic stresses has an impact on posttransplant survival. There is keen interest in characterizing frailty in lung transplantation, both to determine which patients are suitable candidates for listing and also to prepare for their care in the aftermath of lung transplantation.

Lung transplantation: candidate selection and timing of transplant.

Purpose Of Review: Over the past two decades, lung transplant has become the mainstay of treatment for several end-stage lung diseases. As the field continues to evolve, the criteria for referral and listing have also changed. The last update to these guidelines was in 2014 and several studies since then have changed how patients are transplanted.

Incidentally Detected Malignancies in Lung Transplant Explants.

Unlabelled: Active malignancy diagnosed within 5 years is an absolute contraindication for lung transplantation. In this study, we evaluated the rate of incidental malignancies detected in explanted lungs at our institution and assessed the posttransplant survival in patients with nonsmall cell lung cancer (NSCLC).

Methods: A retrospective chart review of lung transplant recipients at our institution from February 1999 to June 2017 was conducted.

Low-dose cadmium potentiates lung inflammatory response to 2009 pandemic H1N1 influenza virus in mice.

Cadmium (Cd) is a toxic, pro-inflammatory metal ubiquitous in the diet that accumulates in body organs due to inefficient elimination. Responses to influenza virus infection are variable, particularly severity of pneumonia. We used a murine model of chronic low-dose oral exposure to Cd to test if increased lung tissue Cd worsened inflammation in response to sub-lethal H1N1 infection.

Transmission of Eastern Equine Encephalitis Virus From an Organ Donor to 3 Transplant Recipients.

Background: In fall 2017, 3 solid organ transplant (SOT) recipients from a common donor developed encephalitis within 1 week of transplantation, prompting suspicion of transplant-transmitted infection. Eastern equine encephalitis virus (EEEV) infection was identified during testing of endomyocardial tissue from the heart recipient.

Methods: We reviewed medical records of the organ donor and transplant recipients and tested serum, whole blood, cerebrospinal fluid, and tissue from the donor and recipients for evidence of EEEV infection by multiple assays.

Selenium supplementation prevents metabolic and transcriptomic responses to cadmium in mouse lung.

Background: The protective effect of selenium (Se) on cadmium (Cd) toxicity is well documented, but underlying mechanisms are unclear.

Methods: Male mice fed standard diet were given Cd (CdCl, 18 μmol/L) in drinking water with or without Se (NaSeO 20 μmol/L) for 16 weeks. Lungs were analyzed for Cd concentration, transcriptomics and metabolomics.

Effect of positive perioperative donor and recipient respiratory bacterial cultures on early post-transplant outcomes in lung transplant recipients.

Background: It is standard practice to administer prophylactic antibiotics post lung transplantation. However, no studies have evaluated the impact of culture positivity. The purpose of this study was to evaluate early post-transplant outcomes of culture-positive and culture-negative lung transplant (LT) recipients and the appropriateness of the empiric regimens used.

Two common human CLDN5 alleles encode different open reading frames but produce one protein isoform.

Claudins provide tight junction barrier selectivity. The human CLDN5 gene contains a high-frequency single-nucleotide polymorphism (rs885985), where the G allele codes for glutamine (Q) and the A allele codes for an amber stop codon. Thus, these different CLDN5 alleles define nested open reading frames (ORFs) encoding claudin-5 proteins that are 303 or 218 amino acids in length.

Nuclear Thioredoxin-1 Overexpression Attenuates Alcohol-Mediated Nrf2 Signaling and Lung Fibrosis.

Background: Alcohol abuse, which impairs antioxidant defenses and promotes acute lung injury, increases Nrf2 nuclear translocation but nevertheless inhibits its activation of the antioxidant response element (ARE). Thioredoxin-1 (Trx1) is required for optimal Nrf2 binding and activation of the ARE, and we hypothesized that its inhibition contributes to impaired Nrf2-ARE signaling in the alcoholic lung.

Methods: Lung tissue and primary lung fibroblasts (PLFs) were isolated from C57/BL6 wild-type (WT) and transgenic mice overexpressing the human Trx1 gene with a nuclear localizing sequence (NLS-Tg); some mice consumed alcohol in water prior to lung tissue and PLF isolation; in some mice, acute lung injury was induced with intratracheal bleomycin.

Low-dose oral cadmium increases airway reactivity and lung neuronal gene expression in mice.

Inhalation of cadmium (Cd) is associated with lung diseases, but less is known concerning pulmonary effects of Cd found in the diet. Cd has a decades-long half-life in humans and significant bioaccumulation occurs with chronic dietary intake. We exposed mice to low-dose CdCl2 (10 mg/L in drinking water) for 20 weeks, which increased lung Cd to a level similar to that of nonoccupationally exposed adult humans.

Epstein-Barr Virus-Associated Pulmonary Smooth Muscle Tumor After Lung Transplantation.

We report an Epstein-Barr virus (EBV)-associated pulmonary posttransplant smooth muscle tumor arising in the left lung of a 71-year-old bilateral lung transplant recipient nearly 3 years after transplantation, treated with thoracoscopic wedge resection. Four previous smooth muscle tumors have been reported following lung transplantation. To our knowledge, this is the first reported case of an EBV-positive posttransplant smooth muscle tumor within the transplanted lung.

TGFβ1 mediates alcohol-induced Nrf2 suppression in lung fibroblasts.

Background: Chronic alcohol ingestion induces the expression of transforming growth factor beta-1(TGFβ1), inhibits nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated activation of the antioxidant response element (ARE), depletes alveolar glutathione pools, and potentiates acute lung injury. In this study, we examined the mechanistic relationship between TGFβ1 and Nrf2-ARE signaling in the experimental alcoholic lung.

Methods: Wild-type mice were treated ± alcohol in drinking water for 8 weeks and their lungs were assessed for Nrf2 expression.

Aging promotes pro-fibrotic matrix production and increases fibrocyte recruitment during acute lung injury.

Fibrotic lung diseases increase with age. Previously we determined that senescence increases tissue expression of fibronectin EDA (Fn-EDA) and decreases fibroblast expression of Thy-1, and that fibrocytes contribute to fibrosis following bleomycin-induced lung injury in mice. In this study we hypothesized that fibroblasts lacking Thy-1 expression produce an extracellular matrix that promotes fibrocyte retention and myofibroblast transdifferentiation, thereby promoting fibrogenesis.

Predisposition for disrepair in the aged lung.

Introduction: Idiopathic pulmonary fibrosis (IPF) is a devastating progressive lung disease with an average survival of only 3 to 5 years. The mechanisms underlying the initiation and progression of IPF are poorly understood, and treatments available have only modest effect on disease progression. Interestingly, the incidence of IPF is approximately 60 times more common in individuals aged 75 years and older, but the mechanism by which aging promotes fibrosis is unclear.