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Your search keyword '"Mohr, Alicia M."' showing total 142 results
Start Over Author "Mohr, Alicia M." Publisher lippincott williams & wilkins
142 results on '"Mohr, Alicia M."'

1. Persistence and Sexual Dimorphism of Gut Dysbiosis and Pathobiome after Sepsis and Trauma.

Author

Munley, Jennifer A., Gwoncheol Park, Kelly, Lauren S., Kannan, Kolenkode B., Mankowski, Robert T., Casadesus, Gemma, Chakrabarty, Paramita, Wallet, Shannon M., Maile, Robert, Bible, Letitia E., Bo Wang, Moldawer, Lyle L., Mohr, Alicia M., Nagpal, Ravinder, and Efron, Philip A.

Abstract

Objective: To evaluate the persistence of intestinal microbiome dysbiosis and gut-plasma metabolomic perturbations following severe trauma or sepsis weeks after admission in patients experiencing chronic critical illness (CCI). Summary: Trauma and sepsis can lead to gut dysbiosis and alterations in the plasma and fecal metabolome. However, the impact of these perturbations and correlations between gut dysbiosis and the plasma metabolome in chronic critical illness have not been studied. Methods: A prospective observational cohort study was performed with healthy subjects, severe trauma patients, and patients with sepsis residing in an intensive care unit for 2 to 3 weeks. A highthroughput multi-omics approach was utilized to evaluate the gut microbial and gut-plasma metabolite responses in critically ill trauma and sepsis patients 14 to 21 days after intensive care unit admission. Results: Patients in the sepsis and trauma cohorts demonstrated strikingly depleted gut microbiome diversity, with significant alterations and specific pathobiome patterns in the microbiota composition compared to healthy subjects. Further subgroup analyses based on sex revealed resistance to changes in microbiome diversity among female trauma patients compared to healthy counterparts. Sex-specific changes in fecal metabolites were also observed after trauma and sepsis, while plasma metabolite changes were similar in both males and females. Conclusions: Dysbiosis induced by trauma and sepsis persists up to 14 to 21 days after onset and is sex-specific, underscoring the implication of pathobiome and entero-septic microbial-metabolite perturbations in post-sepsis and posttrauma chronic critical illness. This indicates resilience to infection or injury in females' microbiome and should inform and facilitate future precision/personalized medicine strategies in the intensive care unit. [ABSTRACT FROM AUTHOR]

Published
2024
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2. TRANSCRIPTOMIC DIFFERENCES IN PERIPHERAL MONOCYTE POPULATIONS IN SEPTIC PATIENTS BASED ON OUTCOME.

Author

Barrios, Evan L., Rincon, Jaimar C., Willis, Micah, Polcz, Valerie E., Leary, Jack R., Darden, Dijoia B., Balch, Jeremy A., Larson, Shawn D., Loftus, Tyler J., Mohr, Alicia M., Wallet, Shannon, Brusko, Maigan A., Balzano-Nogueira, Leandro, Guoshuai Cai, Sharma, Ashish, Upchurch Jr., Gilbert R., Kladde, Michael P., Mathews, Clayton E., Maile, Robert, and Moldawer, Lyle L.

Published
2024
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11. Sex differences associate with late microbiome alterations after murine surgical sepsis.

Author

Efron, Philip Alexander, Darden, Dijoia B, Li, Eric C, Munley, Jennifer, Kelly, Lauren, Fenner, Brittany, Nacionales, Dina C, Ungaro, Ricardo F, Dirain, Marvin L, Rincon, Jaimar, Mankowski, Robert T, Leeuwenburgh, Christiaan, Moore, Fredrick A, Brakenridge, Scott C, Foster, Thomas C, Laitano, Orlando, Casadesus, Gemma, Moldawer, Lyle L, Mohr, Alicia M, and Thomas, Ryan M

Published
2022
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14. Identification of unique microRNA expression patterns in bone marrow hematopoietic stem and progenitor cells after hemorrhagic shock and multiple injuries in young and old adult mice.

Author

Darden, Dijoia B., Mira, Juan C., Lopez, Maria-Cecilia, Stortz, Julie A., Fenner, Brittany P., Kelly, Lauren S., Nacionales, Dina C., Budharaju, Ashrita, Loftus, Tyler J., Baker, Henry V., Moore, Frederick A., Brakenridge, Scott C., Moldawer, Lyle L., Mohr, Alicia M., and Efron, Philip A.

Published
2021
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15. Biomarker Evidence of the Persistent Inflammation, Immunosuppression and Catabolism Syndrome (PICS) in Chronic Critical Illness (CCI) After Surgical Sepsis.

Author

Darden, Dijoia B., Brakenridge, Scott C., Efron, Philip A., Ghita, Gabriela L., Fenner, Brittany P., Kelly, Lauren S., Mohr, Alicia M., Moldawer, Lyle L., and Moore, Frederick A.

Abstract

Objective: To analyze serial biomarkers of the persistent inflammation, immunosuppression, and catabolism syndrome (PICS) to gain insight into the pathobiology of chronic critical illness (CCI) after surgical sepsis. Background: Although early deaths after surgical intensive care unit sepsis have decreased and most survivors rapidly recover (RAP), one third develop the adverse clinical trajectory of CCI. However, the underlying pathobiology of its dismal long-term outcomes remains unclear. Methods: PICS biomarkers over 14 days from 124 CCI and 225 RAP sepsis survivors were analyzed to determine associations and prediction models for (1) CCI (≥14 intensive care unit days with organ dysfunction) and (2) dismal 1-year outcomes (Zubrod 4/5 performance scores). Clinical prediction models were created using PIRO variables (predisposition, insult, response, and organ dysfunction). Biomarkers were then added to determine if they strengthened predictions. Results: CCI (vs RAP) and Zubrod 4/5 (vs Zubrod 0–3) cohorts had greater elevations in biomarkers of inflammation (interleukin [IL]-6, IL-8, interferon gamma-induced protein [IP-10], monocyte chemoattractant protein 1), immunosuppression (IL-10, soluble programmed death ligand-1), stress metabolism (C-reactive protein, glucagon-like peptide 1), and angiogenesis (angiopoietin-2, vascular endothelial growth factor, vascular endothelial growth factor receptor-1, stromal cell-derived factor) at most time-points. Clinical models predicted CCI on day 4 (area under the receiver operating characteristics curve [AUC] = 0.89) and 1 year Zubrod 4/5 on day 7 (AUC = 0.80). IL-10 and IP-10 on day 4 minimally improved prediction of CCI (AUC = 0.90). However, IL-10, IL-6, IL-8, monocyte chemoattractant protein 1, IP-10, angiopoietin-2, glucagon-like peptide 1, soluble programmed death ligand-1, and stromal cell-derived factor on day 7 considerably improved the prediction of Zubrod 4/5 status (AUC = 0.88). Conclusions: Persistent elevations of PICS biomarkers in the CCI and Zubrod 4/5 cohorts and their improved prediction of Zubrod 4/5 validate that PICS plays a role in CCI pathobiology. [ABSTRACT FROM AUTHOR]

Published
2021
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18. SINGLE-CELL RNA-SEQ OF HUMAN MYELOID-DERIVED SUPPRESSOR CELLS IN LATE SEPSIS REVEALS MULTIPLE SUBSETS WITH UNIQUE TRANSCRIPTIONAL RESPONSES: A PILOT STUDY.

Author

Darden, Dijoia B., Bacher, Rhonda, Brusko, Maigan A., Knight, Parker, Hawkins, Russell B., Cox, Michael C., Dirain, Marvin L., Ungaro, Ricardo, Nacionales, Dina C., Rincon, Jaimar C., Gauthier, Marie-Pierre L., Kladde, Michael, Bihorac, Azra, Brusko, Todd M., Moore, Frederick A., Brakenridge, Scott C., Mohr, Alicia M., Moldawer, Lyle L., and Efron, Philip A.

Published
2021
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19. SEPTIC STABILITY? GUT MICROBIOTA IN YOUNG ADULT MICE MAINTAINS OVERALL STABILITY AFTER SEPSIS COMPARED TO OLD ADULT MICE.

Author

Mankowski, Robert T., Thomas, Ryan M., Darden, Dijoia B., Gharaibeh, Raad Z., Hawkins, Russell B., Cox, Michael C., Apple, Camille, Nacionales, Dina C., Ungaro, Ricardo F., Dirain, Marvin L., Moore, Fredrick A., Leeuwenburgh, Christiaan, Brakenridge, Scott C., Clanton, Thomas L., Laitano, Orlando, Moldawer, Lyle L., Mohr, Alicia M., and Efron, Philip A.

Published
2021
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24. Old Mice Demonstrate Organ Dysfunction as well as Prolonged Inflammation, Immunosuppression, and Weight Loss in a Modified Surgical Sepsis Model.

Author

Stortz, Julie A., Hollen, McKenzie K., Nacionales, Dina C., Horiguchi, Hiroyuki, Ungaro, Ricardo, Dirain, Marvin L., Wang, Zhongkai, Wu, Quran, Wu, Kevin K., Kumar, Ashok, Foster, Thomas C., Stewart, Brian D., Ross, Julia A., Segal, Marc, Bihorac, Azra, Brakenridge, Scott, Moore, Frederick A., Wohlgemuth, Stephanie E., Leeuwenburgh, Christiaan, and Mohr, Alicia M.

Published
2019
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25. Current Epidemiology of Surgical Sepsis: Discordance Between Inpatient Mortality and 1-year Outcomes.

Author

Brakenridge, Scott C., Efron, Philip A., Cox, Michael C., Stortz, Julie A., Hawkins, Russell B., Ghita, Gabriela, Gardner, Anna, Mohr, Alicia M., Anton, Stephen D., Moldawer, Lyle L., and Moore, Frederick A.

Abstract

Supplemental Digital Content is available in the text Objective: We sought to compare traditional inpatient outcomes to long-term functional outcomes and mortality of surgical intensive care unit (SICU) patients with sepsis. Summary of Background Data: As inpatient sepsis mortality declines, an increasing number of initial sepsis survivors now progress into a state of chronic critical illness (CCI) and their post-discharge outcomes are unclear. Methods: We performed a prospective, longitudinal cohort study of SICU patients with sepsis. Results: Among this recent cohort of 301 septic SICU patients, 30-day mortality was 9.6%. Only 13 (4%) patients died within 14 days, primarily of refractory multiple organ failure (62%). The majority (n = 189, 63%) exhibited a rapid recovery (RAP), whereas 99 (33%) developed CCI. CCI patients were older, with greater comorbidities, and more severe and persistent organ dysfunction than RAP patients (all P < 0.01). At 12 months, overall cohort performance status was persistently worse than presepsis baseline (WHO/Zubrod score 1.4 ± 0.08 vs 2.2 ± 0.23, P > 0.0001) and mortality was 20.9%. Of note at 12 months, the CCI cohort had persistent severely impaired performance status and a much higher mortality (41.4%) than those with RAP (4.8%) after controlling for age and comorbidity burden (Cox hazard ratio 1.27; 95% confidence interval, 1.14–1.41, P < 0.0001). Among CCI patients, independent risk factors for death by 12 months included severity of comorbidities and persistent organ dysfunction (sequential organ failure assessment ≥6) at day 14 after sepsis onset. Conclusions: There is discordance between low inpatient mortality and poor long-term outcomes after surgical sepsis, especially among older adults, increasing comorbidity burden and patients that develop CCI. This represents important information when discussing expected outcomes of surgical patients who experience a complicated clinical course owing to sepsis. [ABSTRACT FROM AUTHOR]

Published
2019
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30. EVIDENCE FOR PERSISTENT IMMUNE SUPPRESSION IN PATIENTS WHO DEVELOP CHRONIC CRITICAL ILLNESS AFTER SEPSIS.

Author

Stortz, Julie A., Murphy, Tyler J., Raymond, Steven L., Mira, Juan C., Ungaro, Ricardo, Dirain, Marvin L., Nacionales, Dina C., Loftus, Tyler J., Zhongkai Wang, Ozrazgat-Baslanti, Tezcan, Ghita, Gabriela L., Brumback, Babette A., Mohr, Alicia M., Bihorac, Azra, Efron, Philip A., Moldawer, Lyle L., Moore, Frederick A., and Brakenridge, Scott C.

Published
2018
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33. Benchmarking clinical outcomes and the immunocatabolic phenotype of chronic critical illness after sepsis in surgical intensive care unit patients.

Author

Stortz, Julie A., Mira, Juan C., Raymond, Steven L., Loftus, Tyler J., Ozrazgat-Baslanti, Tezcan, Zhongkai Wang, Ghita, Gabriela L., Leeuwenburgh, Christiaan, Segal, Mark S., Bihorac, Azra, Brumback, Babette A., Mohr, Alicia M., Efron, Philip A., Moldawer, Lyle L., Moore, Frederick A., Brakenridge, Scott C., and Wang, Zhongkai

Published
2018
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42. Human Myeloid-derived Suppressor Cells are Associated With Chronic Immune Suppression After Severe Sepsis/Septic Shock.

Author

Mathias, Brittany, Delmas, Amber L., Ozrazgat-Baslanti, Tezcan, Vanzant, Erin L., Szpila, Benjamin E., Mohr, Alicia M., Moore, Frederick A., Brakenridge, Scott C., Brumback, Babette A., Moldawer, Lyle L., and Efron, Philip A.

Abstract

Objective: We hypothesized that after sepsis in humans, MDSCs will be persistently increased, functionally immunosuppressive, and associated with adverse clinical outcomes. Background: Cancer and sepsis have surprisingly similar immunologic responses and equally dismal long term consequences. In cancer, increased myeloid-derived suppressor cells (MDSCs) induce detrimental immunosuppression, but little is known about the role of MDSCs after sepsis. Methods: Blood was obtained from 74 patients within 12 hours of severe sepsis/septic shock (SS/SS), and at set intervals out to 28 days, and also in 18 healthy controls. MDSCs were phenotyped for cell surface receptor expression and enriched by cell sorting. Functional and genome-wide expression analyses were performed. Multiple logistic regression analysis was conducted to determine if increased MDSC appearance was associated with in-hospital and long-term outcomes. Results: After SS/SS, CD33+CD11b+HLA-DR−/low MDSCs were dramatically increased out to 28 days (P < 0.05). When co-cultured with MDSCs from SS/SS patients, antigen-driven T-cell proliferation and TH1/TH2 cytokine production were suppressed (P < 0.05). Additionally, septic MDSCs had suppressed HLA gene expression and up-regulated ARG1 expression (P < 0.05). Finally, SS/SS patients with persistent increased percentages of blood MDSCs had increased nosocomial infections, prolonged intensive care unit stays, and poor functional status at discharge (P < 0.05). Conclusions: After SS/SS in humans, circulating MDSCs are persistently increased, functionally immunosuppressive, and associated with adverse outcomes. This novel observation warrants further studies. As observed in cancer immunotherapy, MDSCs could be a novel component in multimodality immunotherapy targeting detrimental inflammation and immunosuppression after SS/SS to improve currently observed dismal long-term outcomes. [ABSTRACT FROM AUTHOR]

Published
2017
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