Browsing by Author "Fowler, Vance G., Jr."

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    An integrated clinico-metabolomic model improves prediction of death in sepsis
    (American Association for the Advancement of Science, 2013) Langley, Raymond J.; Tsalik, Ephraim L.; van Velkinburgh, Jennifer C.; Glickman, Seth W.; Rice, Brandon J.; Wang, Chunping; Chen, Bo; Carin, Lawrence; Suarez, Arturo; Mohney, Robert P.; Freeman, Debra H.; Wang, Mu; You, Jinsam; Wulff, Jacob; Thompson, J. Will; Moseley, M. Arthur; Reisinger, Stephanie; Edmonds, Brian T.; Grinnell, Brian; Nelson, David R.; Dinwiddie, Darrell L.; Miller, Neil A.; Saunders, Carol J.; Soden, Sarah S.; Rogers, Angela J.; Gazourian, Lee; Fredenburgh, Laura E.; Massaro, Anthony F.; Baron, Rebecca M.; Choi, Augustine M. K.; Corey, G. Ralph; Ginsburg, Geoffrey S.; Cairns, Charles B.; Otero, Ronny M.; Fowler, Vance G., Jr.; Rivers, Emanuel P.; Woods, Christopher W.; Kingsmore, Stephen F.; Medicine, School of Medicine
    Sepsis is a common cause of death, but outcomes in individual patients are difficult to predict. Elucidating the molecular processes that differ between sepsis patients who survive and those who die may permit more appropriate treatments to be deployed. We examined the clinical features and the plasma metabolome and proteome of patients with and without community-acquired sepsis, upon their arrival at hospital emergency departments and 24 hours later. The metabolomes and proteomes of patients at hospital admittance who would ultimately die differed markedly from those of patients who would survive. The different profiles of proteins and metabolites clustered into the following groups: fatty acid transport and β-oxidation, gluconeogenesis, and the citric acid cycle. They differed consistently among several sets of patients, and diverged more as death approached. In contrast, the metabolomes and proteomes of surviving patients with mild sepsis did not differ from survivors with severe sepsis or septic shock. An algorithm derived from clinical features together with measurements of five metabolites predicted patient survival. This algorithm may help to guide the treatment of individual patients with sepsis.
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    Clinical Utility of Plasma Microbial Cell-Free DNA Sequencing Among Immunocompromised Patients With Pneumonia
    (Oxford University Press, 2024-07-22) Madut, Deng B.; Chemaly, Roy F.; Dadwal, Sanjeet S.; Hill, Joshua A.; Lee, Yeon Joo; Haidar, Ghady; Luk, Alfred; Drelick, Alexander; Chin-Hong, Peter V.; Benamu, Esther; Khawaja, Fareed; Nanayakkara, Deepa; Papanicolaou, Genovefa A.; Butkus Small, Catherine; Fung, Monica; Barron, Michelle; Davis, Thomas; McClain, Micah T.; Maziarz, Eileen K.; Bedoya, Armando D.; Gilstrap, Daniel L.; Todd, Jamie L.; Barkauskas, Christina E.; Heldman, Madeleine R.; Bigelow, Robert; Leimberger, Jeffrey D.; Tsalik, Ephraim L.; Wolf, Olivia; Mughar, Mona; Lau, Constance; Noll, Nicholas; Hollemon, Desiree; Duttagupta, Radha; Lupu, Daniel S.; Bercovici, Sivan; Perkins, Bradley A.; Blauwkamp, Timothy A.; Fowler, Vance G., Jr.; Holland, Thomas L.; Bergin, Stephen P.; Pathology and Laboratory Medicine, School of Medicine
    Background: Plasma microbial cell-free DNA (mcfDNA) sequencing can establish the etiology of multiple infectious syndromes by identifying microbial DNA in plasma. However, data are needed to define the clinical scenarios where this tool offers the highest clinical benefit. Methods: We conducted a prospective multicenter observational study that evaluated the impact of plasma mcfDNA sequencing compared with usual care testing among adults with hematologic malignancies. This is a secondary analysis of an expanded cohort that evaluated the clinical utility of plasma mcfDNA sequencing across prespecified and adjudicated outcomes. We examined the percentage of participants for whom plasma mcfDNA sequencing identified a probable cause of pneumonia or clinically relevant nonpneumonia infection. We then assessed potential changes in antimicrobial therapy based on plasma mcfDNA sequencing results and the potential for early mcfDNA testing to avoid bronchoscopy and its associated adverse events. Results: Of 223 participants, at least 1 microbial detection by plasma mcfDNA sequencing was adjudicated as a probable cause of pneumonia in 57 (25.6%) and a clinically relevant nonpneumonia infection in 88 (39.5%). A probable cause of pneumonia was exclusively identified by plasma mcfDNA sequencing in 23 (10.3%) participants. Antimicrobial therapy would have changed for 41 (18.4%) participants had plasma mcfDNA results been available in real time. Among the 57 participants with a probable cause of pneumonia identified by plasma mcfDNA sequencing, bronchoscopy identified no additional probable cause of pneumonia in 52 (91.2%). Conclusions: Plasma mcfDNA sequencing could improve management of both pneumonia and other concurrent infections in immunocompromised patients with suspected pneumonia.
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    Plasma Microbial Cell-Free DNA Sequencing in Immunocompromised Patients With Pneumonia: A Prospective Observational Study
    (Oxford University Press, 2024) Bergin, Stephen P.; Chemaly, Roy F.; Dadwal, Sanjeet S.; Hill, Joshua A.; Lee, Yeon Joo; Haidar, Ghady; Luk, Alfred; Drelick, Alexander; Chin-Hong, Peter V.; Benamu, Esther; Khawaja, Fareed; Nanayakkara, Deepa; Papanicolaou, Genovefa A.; Butkus Small, Catherine; Fung, Monica; Barron, Michelle A.; Davis, Thomas; McClain, Micah T.; Maziarz, Eileen K.; Madut, Deng B.; Bedoya, Armando D.; Gilstrap, Daniel L.; Todd, Jamie L.; Barkauskas, Christina E.; Bigelow, Robert; Leimberger, Jeffrey D.; Tsalik, Ephraim L.; Wolf, Olivia; Mughar, Mona; Hollemon, Desiree; Duttagupta, Radha; Lupu, Daniel S.; Bercovici, Sivan; Perkins, Bradley A.; Blauwkamp, Timothy A.; Fowler, Vance G., Jr.; Holland, Thomas L.; Pathology and Laboratory Medicine, School of Medicine
    Background: Pneumonia is a common cause of morbidity and mortality, yet a causative pathogen is identified in a minority of cases. Plasma microbial cell-free DNA sequencing may improve diagnostic yield in immunocompromised patients with pneumonia. Methods: In this prospective, multicenter, observational study of immunocompromised adults undergoing bronchoscopy to establish a pneumonia etiology, plasma microbial cell-free DNA sequencing was compared to standardized usual care testing. Pneumonia etiology was adjudicated by a blinded independent committee. The primary outcome, additive diagnostic value, was assessed in the Per Protocol population (patients with complete testing results and no major protocol deviations) and defined as the percent of patients with an etiology of pneumonia exclusively identified by plasma microbial cell-free DNA sequencing. Clinical additive diagnostic value was assessed in the Per Protocol subgroup with negative usual care testing. Results: Of 257 patients, 173 met Per Protocol criteria. A pneumonia etiology was identified by usual care in 52/173 (30.1%), plasma microbial cell-free DNA sequencing in 49/173 (28.3%) and the combination of both in 73/173 (42.2%) patients. Plasma microbial cell-free DNA sequencing exclusively identified an etiology of pneumonia in 21/173 patients (additive diagnostic value 12.1%, 95% confidence interval [CI], 7.7% to 18.0%, P < .001). In the Per Protocol subgroup with negative usual care testing, plasma microbial cell-free DNA sequencing identified a pneumonia etiology in 21/121 patients (clinical additive diagnostic value 17.4%, 95% CI, 11.1% to 25.3%). Conclusions: Non-invasive plasma microbial cell-free DNA sequencing significantly increased diagnostic yield in immunocompromised patients with pneumonia undergoing bronchoscopy and extensive microbiologic and molecular testing.