ORCID Profile
0000-0002-9429-4702
Current Organisation
Vanderbilt University Medical Center
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Publisher: American Society for Clinical Investigation
Date: 22-06-2021
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2022
Publisher: American Association for the Advancement of Science (AAAS)
Date: 10-07-2020
Abstract: Single-cell RNA sequencing provides new insights into pathologic epithelial and mesenchymal remodeling in the human lung.
Publisher: American Thoracic Society
Date: 15-08-2017
Publisher: Springer Science and Business Media LLC
Date: 28-05-2021
DOI: 10.1186/S12882-021-02400-3
Abstract: Acute kidney injury (AKI) and obesity are independent risk factors for chronic kidney disease (CKD). This study aimed to determine if obesity modifies risk for CKD outcomes after AKI. This prospective multisite cohort study followed adult survivors after hospitalization, with or without AKI. The primary outcome was a combined CKD event of incident CKD, progression of CKD and kidney failure, examined using time-to-event Cox proportional hazards models, adjusted for diabetes status, age, pre-existing CKD, cardiovascular disease status and intensive care unit admission, and stratified by study center. Body mass index (BMI) was added as an interaction term to examine effect modification by body size. The cohort included 769 participants with AKI and 769 matched controls. After median follow-up of 4.3 years, among AKI survivors, the rate of the combined CKD outcome was 84.7 per1000-person-years with BMI ≥30 kg/m 2 , 56.4 per 1000-person-years with BMI 25–29.9 kg/m 2 , and 72.6 per 1000-person-years with BMI 20–24.9 kg/m 2 . AKI was associated with a higher risk of combined CKD outcomes adjusted-HR 2.43 (95%CI 1.87–3.16), with no evidence that this was modified by BMI ( p for interaction = 0.3). After adjustment for competing risk of death, AKI remained associated with a higher risk of the combined CKD outcome (subdistribution-HR 2.27, 95%CI 1.76–2.92) and similarly, there was no detectable effect of BMI modifying this risk. In this post-hospitalization cohort, we found no evidence for obesity modifying the association between AKI and development or progression of CKD.
Publisher: Elsevier BV
Date: 04-2022
Publisher: Springer Science and Business Media LLC
Date: 06-2022
DOI: 10.1038/S41591-022-01843-X
Abstract: Research and practice in critical care medicine have long been defined by syndromes, which, despite being clinically recognizable entities, are, in fact, loose amalgams of heterogeneous states that may respond differently to therapy. Mounting translational evidence-supported by research on respiratory failure due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-suggests that the current syndrome-based framework of critical illness should be reconsidered. Here we discuss recent findings from basic science and clinical research in critical care and explore how these might inform a new conceptual model of critical illness. De-emphasizing syndromes, we focus on the underlying biological changes that underpin critical illness states and that may be amenable to treatment. We hypothesize that such an approach will accelerate critical care research, leading to a richer understanding of the pathobiology of critical illness and of the key determinants of patient outcomes. This, in turn, will support the design of more effective clinical trials and inform a more precise and more effective practice at the bedside.
Publisher: American Thoracic Society
Date: 24-07-2023
Publisher: Springer Science and Business Media LLC
Date: 18-11-2020
Publisher: Elsevier BV
Date: 04-2011
Publisher: American Physiological Society
Date: 06-2004
DOI: 10.1152/AJPLUNG.00304.2003
Abstract: Proteomics is the large-scale analysis of protein profiles. This approach has not yet been reported in the study of acute lung injury (ALI). This study details protein profiles in plasma and pulmonary edema fluid (EF) from 16 ALI patients and plasma and bronchoalveolar lavage fluid (BALF) from 12 normal subjects. More than 300 distinct protein spots were evident in the EF and BALF of both normal subjects and ALI patients. Of these, 158 were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. In the plasma and EF protein profile of ALI patients, there were multiple qualitative changes. For instance, in all normal subjects, but in only one of the ALI patients, seven distinct surfactant protein A isoforms were evident. Nearly all ALI patients also had protein spots that indicate truncation or other posttranslational modifications. Several of these novel changes could serve as new biomarkers of lung injury.
Publisher: Cold Spring Harbor Laboratory
Date: 06-09-2019
DOI: 10.1101/753806
Abstract: Pulmonary fibrosis is a form of chronic lung disease characterized by pathologic epithelial remodeling and accumulation of extracellular matrix. In order to comprehensively define the cell types, mechanisms and mediators driving fibrotic remodeling in lungs with pulmonary fibrosis, we performed single-cell RNA-sequencing of single-cell suspensions from 10 non-fibrotic control and 20 PF lungs. Analysis of 114,396 cells identified 31 distinct cell types. We report a remarkable shift in epithelial cell phenotypes occurs in the peripheral lung in PF, and identify several previously unrecognized epithelial cell phenotypes including a KRT5 − / KRT17 + , pathologic ECM-producing epithelial cell population that was highly enriched in PF lungs. Multiple fibroblast subtypes were observed to contribute to ECM expansion in a spatially-discrete manner. Together these data provide high-resolution insights into the complexity and plasticity of the distal lung epithelium in human disease, and indicate a ersity of epithelial and mesenchymal cells contribute to pathologic lung fibrosis. Single-cell RNA-sequencing provides new insights into pathologic epithelial and mesenchymal remodeling in the human lung.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2017
DOI: 10.1097/CCM.0000000000002654
Abstract: The primary objective was to conduct a meta-analysis on published observational cohort data describing the association between acetyl-salicylic acid (aspirin) use prior to the onset of sepsis and mortality in hospitalized patients. Studies that reported mortality in patients on aspirin with sepsis with a comparison group of patients with sepsis not on prior aspirin therapy were included. Fifteen studies described hospital-based cohorts ( n = 17,065), whereas one was a large insurance-based database ( n = 683,421). In idual-level patient data were incorporated from all selected studies. Propensity analyses with 1:1 propensity score matching at the study level were performed, using the most consistently available covariates judged to be associated with aspirin. Meta-analyses were performed to estimate the pooled average treatment effect of aspirin on sepsis-related mortality. Use of aspirin was associated with a 7% (95% CI, 2–12% p = 0.005) reduction in the risk of death as shown by meta-analysis with considerable statistical heterogeneity ( I 2 = 61.6%). These results are consistent with effects ranging from a 2% to 12% reduction in mortality risk in patients taking aspirin prior to sepsis onset. This association anticipates results of definitive studies of the use of low-dose aspirin as a strategy for reduction of deaths in patients with sepsis.
Location: United States of America
No related grants have been discovered for Lorraine Ware.