1
|
Basu S, Wei ZJ, Laor A, Bennetts L, Ahmad N, El Khoury AC, Geurtsen J, Neary MP. Health-Related Quality of Life Among Patients Who Have Survived an Episode of Sepsis in the United States: A Systematic Review. Infect Dis Ther 2025; 14:385-400. [PMID: 39862376 PMCID: PMC11829873 DOI: 10.1007/s40121-024-01106-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Accepted: 12/23/2024] [Indexed: 01/27/2025] Open
Abstract
INTRODUCTION Sepsis is a serious condition that may lead to death or profoundly affect the well-being of those who survive. The aim of this systematic review was to identify and summarize evidence on the impact of all-cause sepsis on health-related quality of life (HRQoL), physical, cognitive, and psychological outcomes among sepsis survivors in the USA. METHODS Studies assessing HRQoL, physical, cognitive, and psychological outcomes in patients who survived an episode of sepsis and published from January 1, 2010, to September 30, 2023, were systematically identified through EMBASE, MEDLINE, and MEDLINE In-Process databases, as well as through gray literature. RESULTS Of 2885 records identified, 7 studies (7 publications; N = 180,592 participants) met the eligibility criteria for inclusion in this review. Studies examined the effects of sepsis on the following outcomes of interest: HRQoL (4 studies), physical functioning (5 studies), cognitive status (3 studies), and psychological well-being (3 studies). After 12 months, sepsis survivors who developed chronic critical illness (N = 63) had significantly poorer HRQoL as measured by EuroQoL 5-dimensional (EQ-5D) questionnaire mean utility index score and Short Form 36-item (SF-36) physical and mental summary scores compared with patients who rapidly recovered (N = 110). Among patients admitted to a skilled nursing facility post-sepsis (N = 66,540), 34% and 72.5% had severe or very severe cognitive impairment and dependence to perform activities of daily living, respectively. Significant increase in moderate-to-severe cognitive impairment among severe sepsis survivors (N = 623) before and after sepsis was reported (median 0.9 [IQR: 0.4, 1.4] years; 6.1% and 16.7%, respectively [P < 0.001]). Substantial depression and anxiety symptoms were frequently observed post-sepsis, but with limited evidence for increased burden as assessed by specific psychological measures. CONCLUSION These findings underscore the profound negative impacts of sepsis on patients' HRQoL, ability to perform activities of daily living, and cognitive abilities.
Collapse
Affiliation(s)
- Sanjukta Basu
- Amaris Consulting, 250 Yonge St., Toronto, ON, Canada.
| | | | | | | | - Nina Ahmad
- Janssen Global Services, LLC, Raritan, NJ, USA
| | | | - Jeroen Geurtsen
- Janssen Vaccines and Prevention BV, Leiden, South Holland, The Netherlands
| | | |
Collapse
|
2
|
Pokharel MD, Feng A, Liang Y, Ma W, Aggarwal S, Unwalla H, Black SM, Wang T. Drp1-associated genes implicated in sepsis survival. Front Immunol 2025; 15:1516145. [PMID: 39845954 PMCID: PMC11750657 DOI: 10.3389/fimmu.2024.1516145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 12/12/2024] [Indexed: 01/24/2025] Open
Abstract
Sepsis is a severe and life-threatening medical syndrome that can lead to organ failure and death. Despite advances in medical treatment, current therapies are often inadequate, with high septic mortality rates. Therefore, there is a critical need for reliable prognostic markers to be used in clinical settings to improve the management and outcomes of patients with sepsis. Recent studies have suggested that mitochondrial dynamics, including the processes of mitochondrial fission and fusion, are closely related to the severity of sepsis and the status of inflammation. By monitoring transcriptomic signals related to mitochondrial dynamics, new and reliable biomarkers can be engineered to more accurately predict sepsis survival risk. Such biomarkers would be invaluable in clinical settings, aiding healthcare providers in the early identification of high-risk patients and improving treatment strategies. To achieve this goal, we utilized the major mitochondrial fission regulatory protein dynamin-related protein 1 (Drp1, gene code DNM1L) and identified Drp1-associated genes that are enriched with sepsis survival genes. A 12-gene signature (GS) was established as a differentially expressed gene (DEG)-based GS. Next, we compared genes of proteins that interact with Drp1 to sepsis survival genes and identified 7 common genes, establishing a GS we term as protein-protein interaction (PPI)-based GS. To evaluate if these GSs can predict sepsis survival, we used publicly available human blood transcriptomic datasets from sepsis patients. We confirmed that both GSs can successfully predict sepsis survival in both discovery and validation cohorts with high sensitivity and specificity, with the PPI-based GS showing enhanced prognostic performance. Together, this study successfully engineers a new and validated blood-borne biomarker (PPI-based 7-gene GS) for sepsis survival risk prediction. This biomarker holds the potential for improving the early identification of high-risk sepsis patients and optimizing personalized treatment strategies to reduce sepsis mortality.
Collapse
Affiliation(s)
- Marissa D. Pokharel
- Center for Translational Science, Florida International University, Port Saint Lucie, FL, United States
- Department of Cellular and Molecular Medicine, Florida International University, Miami, FL, United States
| | - Anlin Feng
- Center for Translational Science, Florida International University, Port Saint Lucie, FL, United States
- Department of Environmental Health Sciences, Florida International University, Miami, FL, United States
| | - Ying Liang
- Center for Translational Science, Florida International University, Port Saint Lucie, FL, United States
- Department of Environmental Health Sciences, Florida International University, Miami, FL, United States
| | - Wenli Ma
- Center for Translational Science, Florida International University, Port Saint Lucie, FL, United States
- Department of Environmental Health Sciences, Florida International University, Miami, FL, United States
| | - Saurabh Aggarwal
- Department of Cellular and Molecular Medicine, Florida International University, Miami, FL, United States
| | - Hoshang Unwalla
- Department of Cellular and Molecular Medicine, Florida International University, Miami, FL, United States
| | - Stephen M. Black
- Center for Translational Science, Florida International University, Port Saint Lucie, FL, United States
- Department of Cellular and Molecular Medicine, Florida International University, Miami, FL, United States
- Department of Environmental Health Sciences, Florida International University, Miami, FL, United States
| | - Ting Wang
- Center for Translational Science, Florida International University, Port Saint Lucie, FL, United States
- Department of Cellular and Molecular Medicine, Florida International University, Miami, FL, United States
- Department of Environmental Health Sciences, Florida International University, Miami, FL, United States
| |
Collapse
|
3
|
Wang L, Mi LY, Chen XY, He HW, Long Y. Effects of different antiplatelet therapy drugs on platelet activation and platelet-leukocyte aggregate formation in early septic ARDS. BMC Pharmacol Toxicol 2025; 26:4. [PMID: 39762913 PMCID: PMC11705853 DOI: 10.1186/s40360-024-00806-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Accepted: 10/22/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND In patients with sepsis, platelets are activated and adhere to neutrophils, forming platelet-leukocyte aggregates (PLAs) that lead to the development of MODS. ARDS is one of the main manifestations of septic MODS. We designed this study to explore the effects of different anti-plate therapy drugs on platelet activation and platelet-leukocyte aggregate (PLA) formation in the early stage of septic ARDS. METHODS Sixty adult male SD rats were randomly divided into: Control group; ARDS group, ARDS + aspirin group, ARDS + clopidogrel group and ARDS + tirofiban group. ARDS was performed via instill lipopolysaccharide (LPS) intratracheally at a dose of 5 mg/kg. Aspirin or clopidogrel were given by gavage immediately after modeling. Tirofiban were given by intraperitoneal injection immediately after modeling. Rats in every group were euthanized by rapid decapitation 6 h after modeling. Platelet activation and PLA were assessed using flow cytometry and immunofluorescence staining. Histology of lung was performed by hematoxylin and eosin staining. RESULTS Aspirin, clopidogrel and tirofiban decreased CRP, IL-1 and TNF-α significantly in septic ARDS (P < 0.05). Aspirin, clopidogrel and tirofiban decreased platelet function and ratio of wet/dry significantly in septic ARDS (P < 0.05). Aspirin, clopidogrel and tirofiban increased PaO2 significantly in septic ARDS (P < 0.05). Platelet activation and PLA in the ARDS + aspirin group, ARDS + clopidogrel group and ARDS + tirofiban group decreased significantly compared to the ARDS group (P < 0.05). At 6 h after ARDS operation, obvious histological damage was observed in the lungs. All of these histological changes were quantitatively evaluated using injury scores. Aspirin, clopidogrel and tirofiban reduced the histological damages in ARDS group (P < 0.05). CONCLUSIONS Aspirin, clopidogrel and tirofiban alleviated the inflammatory response and pulmonary edema, reduced platelet function, and alleviated hypoxemia in early septic ARDS. Aspirin, clopidogrel and tirofiban reduced platelet activation and PLA formation in early septic ARDS. Aspirin, clopidogrel and tirofiban ultimately alleviated lung injury in early septic ARDS.
Collapse
Affiliation(s)
- Lu Wang
- Department of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Liang-Yu Mi
- Department of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Xiang-Yu Chen
- Department of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Huai-Wu He
- Department of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Yun Long
- Department of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China.
| |
Collapse
|
4
|
Tilburgs B, Simons KS, Corsten S, Westerhof B, Rettig TCD, Ewalds E, Zegers M, van den Boogaard M. Associations Between Physical, Cognitive, and Mental Health Domains of Post-Intensive Care Syndrome and Quality of Life: A Longitudinal Multicenter Cohort Study. Crit Care Med 2025; 53:e74-e86. [PMID: 39445920 PMCID: PMC11698138 DOI: 10.1097/ccm.0000000000006461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2024]
Abstract
OBJECTIVES To explore associations between the physical, cognitive, and mental post-intensive care syndrome (PICS) health domains with changes in health-related quality of life (HRQoL) following ICU admission. DESIGN A longitudinal prospective multicenter cohort study. SETTING/PATIENTS Patients ( n = 4092) from seven Dutch ICUs. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS At ICU admission, 3 and 12 months post-ICU, patients completed validated questionnaires regarding physical health problems, cognitive health problems, mental health problems, and HRQoL. Composite scores were created for the physical health domain (physical problems and fatigue) and mental health domain (anxiety, depression, and post-traumatic stress disorder). Adjusted multivariable linear regression analyses were performed, including covariables (e.g., patient characteristics, disease severity, pre-ICU HRQoL, etc.) to explore associations between the physical, cognitive, and mental health domains of PICS and changes in HRQoL at 3 and 12 months post-ICU. At 3 months ( n = 3368), physical health problems (β = -0.04 [95% CI, -0.06 to 0.02]; p < 0.001), cognitive health problems (β = -0.05 [95% CI, -0.09 to -0.02]; p < 0.001), and mental health problems (β = -0.08 [95% CI, -0.10 to -0.05]; p < 0.001) were negatively associated with changes in HRQoL. Also, at 12 months ( n = 2950), physical health problems (β = -0.06 [95% CI, -0.08 to -0.03]; p < 0.001), cognitive health problems (β = -0.04 [95% CI, -0.08 to -0.01]; p < 0.015), and mental health problems (β = -0.06 [95% CI, -0.08 to -0.03]; p < 0.001) were negatively associated with changes in HRQoL. CONCLUSIONS PICS symptoms in the physical, cognitive, and mental domains are all negatively associated with changes in HRQoL at 3 and 12 months post-ICU. At 3 months, PICS symptoms in the mental domain seem to have the largest negative associations. At 12 months, the associations of PICS in the mental and physical domains are the same. This implies that daily ICU care and follow-up care should focus on preventing and mitigating health problems across all three PICS domains to prevent a decrease in HRQoL.
Collapse
Affiliation(s)
- Bram Tilburgs
- Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Koen S. Simons
- Department of Intensive Care Medicine, Jeroen Bosch Hospital, ’s-Hertogenbosch, The Netherlands
| | - Stijn Corsten
- Department of Intensive Care Medicine, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands
| | - Brigitte Westerhof
- Department of Intensive Care Medicine, Rijnstate Hospital, Arnhem, The Netherlands
| | - Thijs C. D. Rettig
- Department of Anesthesiology, Intensive Care and Pain Medicine, Amphia Hospital, Breda, The Netherlands
| | - Esther Ewalds
- Department of Intensive Care Medicine, Bernhoven Hospital, Uden, The Netherlands
| | - Marieke Zegers
- Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Mark van den Boogaard
- Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
| |
Collapse
|
5
|
Murata M, Shimizu S, Yamamoto R, Kamitani T, Yamazaki H, Ogawa Y, Fukuhara S, Yasuda H, Yamamoto Y. Steroid Therapy for Patients with Septic Shock: A Multicenter Observational Study Conducted in Japan. Intern Med 2024; 63:3307-3315. [PMID: 38719604 PMCID: PMC11729175 DOI: 10.2169/internalmedicine.1511-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Accepted: 02/25/2024] [Indexed: 12/17/2024] Open
Abstract
Objective The Clinical Practice Guidelines for the Management of Sepsis and Septic Shock weakly recommend steroids for septic shock resistant to fluid resuscitation and vasopressors. This study aimed to describe the clinical practices for septic shock in the real world and to compare the association between the intermittent or continuous infusion of steroids and the prognosis. Methods This was a retrospective cohort study based on the AMOR-VENUS, in which Japanese intensive care unit (ICU) inpatients were enrolled between January and March 2018. Adult patients with sepsis who received vasopressors within 72 h of ICU admission were included. The patients were divided into non-steroid and steroid groups, which were further divided into intermittent and continuous infusion groups. The patient characteristics and details of the steroids are described. To investigate the association between intermittent or continuous infusion, shock reversal, and mortality, logistic regression analyses were performed after adjusting for possible confounding factors. Results A total of 180 patients with septic shock from 18 ICUs were enrolled. The mean age was 69.6 (standard deviation, 14.3) years. Sixty-three patients (35.0%) received steroids (26 intermittently, 37 continuously). In the steroid group, hydrocortisone was used in 85.7%, the median daily dose was 192 mg, and the steroids were administered within 6 h of initiating vasopressor in 71.4%. The adjusted odds ratios of shock reversal on the 7th day and the ICU mortality for continuous versus intermittent infusion were 1.90 (95% confidence interval, 0.43-8.40) and 0.61 (0.10-3.85), respectively. Conclusion There was considerable variation in the criteria for the selection of patients and in the decision to use continuous or intermittent steroid infusion.
Collapse
Affiliation(s)
- Maki Murata
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Japan
| | - Sayaka Shimizu
- Institute for Health Outcomes & Process Evaluation Research (iHope International), Japan
- Section of Clinical Epidemiology, Department of Community Medicine, Graduate School of Medicine, Kyoto University, Japan
| | - Ryohei Yamamoto
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Japan
| | - Tsukasa Kamitani
- Section of Education for Clinical Research, Kyoto University Hospital, Japan
| | - Hajime Yamazaki
- Section of Clinical Epidemiology, Department of Community Medicine, Graduate School of Medicine, Kyoto University, Japan
| | - Yusuke Ogawa
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Japan
| | - Shunichi Fukuhara
- Institute for Health Outcomes & Process Evaluation Research (iHope International), Japan
- Center for Innovative Research for Communities and Clinical Excellence, Fukushima Medical University, Japan
- Department of General Medicine, Shirakawa Satellite for Teaching And Research (STAR), Fukushima Medical University, Japan
- Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health (JHSPH), USA
| | - Hideto Yasuda
- Department of Emergency and Critical Care Medicine, Jichi Medical University Saitama Medical Center, Japan
- Department of Clinical Research Education and Training Unit, Keio University Hospital Clinical and Translational Research Center 17 (CTR), Japan
| | - Yosuke Yamamoto
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Japan
| |
Collapse
|
6
|
Stevenson JA, Murphy TE, Tessier-Sherman B, Pisani MA, Gill TM, Ferrante LE. Feasibility of In-Hospital Administration of a Tool to Predict Persistent Post-ICU Functional Impairment Among Older ICU Survivors: A Pilot Study. CHEST CRITICAL CARE 2024; 2:100093. [PMID: 39822381 PMCID: PMC11737545 DOI: 10.1016/j.chstcc.2024.100093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/19/2025]
Abstract
BACKGROUND A recent international consensus conference called for the development of risk prediction models to identify ICU survivors at increased risk of each of the post-ICU syndrome domains. We previously developed and validated a risk prediction tool for functional impairment after ICU admission among older adults. RESEARCH QUESTION In this pilot study, we assessed the feasibility of administering the risk prediction tool in the hospital to older adults who had just survived critical illness. An exploratory objective was to evaluate whether augmentation of the model with additional hospital-related factors improved discrimination. STUDY DESIGN AND METHODS Between January and October 2020, 50 adults aged 65 years and older underwent in-hospital administration of the risk prediction tool. Survivors were called monthly for 6 months after discharge. Feasibility was defined as completion of all tool components by ≥ 70% of enrolled participants. Persistent functional impairment was defined as failure to return to the functional baseline from before the ICU stay at the 6-month interview based on seven daily activities. The model was sequentially refit after adding three in-hospital factors as predictors, one at a time and then all together. Model discrimination was assessed with receiver operating characteristic curves. RESULTS The tool met the a priori feasibility threshold, with 92.0% of enrolled participants completing all eight components. In the exploratory analysis, the addition of Acute Physiology and Chronic Health Evaluation II score, presence of delirium, and maximum in-hospital mobility resulted in a 5% gain in discrimination that did not achieve statistical significance (area under the receiver operating characteristic curve, 0.75; 95% CI, 0.68-0.82; P = .09). INTERPRETATION Our results indicate that the risk prediction tool is feasible for use in the hospital setting, enabling the identification of ICU survivors at high risk of persistent functional impairment at 6 months after discharge. Augmentation with hospital-related factors improved model discrimination, but did not achieve statistical significance in this pilot study. Future studies should evaluate the augmented model in larger cohorts.
Collapse
Affiliation(s)
| | - Terrence E Murphy
- Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA
| | | | - Margaret A Pisani
- Section of Pulmonary, Critical Care, and Sleep Medicine, New Haven, CT
| | | | - Lauren E Ferrante
- Section of Pulmonary, Critical Care, and Sleep Medicine, New Haven, CT
| |
Collapse
|
7
|
Eisner AE, Witek L, Pajewski NM, Taylor SP, Bundy R, Williamson JD, Jaeger BC, Palakshappa JA. Developing a prediction model for cognitive impairment in older adults following critical illness. BMC Geriatr 2024; 24:982. [PMID: 39614152 DOI: 10.1186/s12877-024-05567-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 11/18/2024] [Indexed: 12/01/2024] Open
Abstract
BACKGROUND New or worsening cognitive impairment or dementia is common in older adults following an episode of critical illness, and screening post-discharge is recommended for those at increased risk. There is a need for prediction models of post-ICU cognitive impairment to guide delivery of screening and support resources to those in greatest need. We sought to develop and internally validate a machine learning model for new cognitive impairment or dementia in older adults after critical illness using electronic health record (EHR) data. METHODS Our cohort included patients > 60 years of age admitted to a large academic health system ICU in North Carolina between 2015 and 2021. Patients were included in the cohort if they were admitted to the ICU for ≥ 48 h with ≥ 2 ambulatory visits prior to hospitalization and at least one visit in the post-discharge year. We used a machine learning model, oblique random survival forests (ORSF), to examine the multivariable association of 54 structured data elements available by 3 months after discharge with incident diagnoses of cognitive impairment or dementia over 1-year. RESULTS In this cohort of 8,299 adults, 22% died and 4.9% were diagnosed with dementia or cognitive impairment within one year. The ORSF model showed reasonable discrimination (c-statistic = 0.83) and stability with little difference in the model's c-statistic across time. CONCLUSION Machine learning using readily available EHR data can predict new cognitive impairment or dementia at 1-year post-ICU discharge in older adults with acceptable accuracy. Further studies are needed to understand how this tool may impact screening for cognitive impairment in the post-discharge period.
Collapse
Affiliation(s)
- Ashley E Eisner
- Department of Internal Medicine, Section on Pulmonology, Critical Care, Allergy & Immunologic Diseases, Wake Forest University School of Medicine, 2 Watlington Hall, 1 Medical Center Boulevard, Winston-Salem, NC, 27157, USA
| | - Lauren Witek
- Informatics and Analytics, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, USA
| | - Nicholas M Pajewski
- Department of Biostatistics and Data Science, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Stephanie P Taylor
- Division of Hospital Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Richa Bundy
- Informatics and Analytics, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, USA
| | - Jeff D Williamson
- Section on Geriatric Medicine and Gerontology, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Byron C Jaeger
- Department of Biostatistics and Data Science, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Jessica A Palakshappa
- Department of Internal Medicine, Section on Pulmonology, Critical Care, Allergy & Immunologic Diseases, Wake Forest University School of Medicine, 2 Watlington Hall, 1 Medical Center Boulevard, Winston-Salem, NC, 27157, USA.
| |
Collapse
|
8
|
Catalão CHR, da Costa LHA, Dos Santos JR, Alberici LC, Falconi-Sobrinho LL, Coimbra NC, Dominguini D, Dal-Pizzol F, Barichello T, Rocha MJA. Mitigating neuroinflammation in cognitive areas: exploring the impact of HMG-CoA reductase inhibitor. Biochem J 2024; 481:1585-1602. [PMID: 39466125 DOI: 10.1042/bcj20240217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 09/20/2024] [Accepted: 10/28/2024] [Indexed: 10/29/2024]
Abstract
Existing literature suggests that infection-specific mechanisms may play a significant role in the onset and progression of dementia, as opposed to the broader phenomenon of systemic inflammation. In addition, 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitors have been proposed as a potential therapeutic approach for sepsis, given their anti-inflammatory and antioxidant properties. We investigated the neuroprotective effect of an HMG-CoA reductase inhibitor (simvastatin) by analyzing neurodegenerative markers, mitochondrial respiration, and neuronal tracing in the prefrontal cortex (PFC) and thalamic nucleus reuniens (RE) of sepsis survivor animals. Adult Wistar rats were subjected to sepsis by cecal ligation and puncture or left non-manipulated. The animals were treated with simvastatin or vehicle for 4 days before and 10 days after surgery. The treatment preserved the non-associative memory (P < 0.05), recovered expression of Smad-3 in the hippocampus (P < 0.05), and prevented increased expression of calpain-1 (hippocampus: P < 0.0001; PFC: P < 0.05) and GSKβ (hippocampus: P < 0.0001; PFC: P < 0.0001) in the brain structures of the sepsis survivor animals. These animals also showed mitochondrial dysfunction and decreased axon terminals in the RE. Simvastatin seems to restore energy metabolism by improving the electron transfer system (ETS) values in the hippocampus (P < 0.01) and the oxidative phosphorylation/ETS (P/E) ratio in the PFC (P < 0.05), in addition to preventing the reduction of axon terminals in survivor animals. These results suggest a potential neuroprotective effect and the importance of considering HMG-CoA reductase inhibitors as a possible adjuvant therapy in sepsis.
Collapse
Affiliation(s)
- Carlos Henrique Rocha Catalão
- Department of Neurosciences and Behavioral Sciences of Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto-SP, Brazil
- Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, U.S.A
- Department of Psychology, Faculty of Philosophy, Sciences and Letters at Ribeirão Preto, University of São Paulo, Ribeirão Preto-SP, Brazil
| | - Luis Henrique Angenendt da Costa
- Department of Neurosciences and Behavioral Sciences of Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto-SP, Brazil
| | - Jonathas Rodrigo Dos Santos
- Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto-SP, Brazil
| | - Luciane Carla Alberici
- Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto-SP, Brazil
| | | | - Norberto Cysne Coimbra
- Department of Pharmacology of Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto-SP, Brazil
| | - Diogo Dominguini
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil
| | - Felipe Dal-Pizzol
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil
| | - Tatiana Barichello
- Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, U.S.A
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil
| | - Maria José Alves Rocha
- Department of Psychology, Faculty of Philosophy, Sciences and Letters at Ribeirão Preto, University of São Paulo, Ribeirão Preto-SP, Brazil
| |
Collapse
|
9
|
Strohl JJ, Carrión J, Huerta PT. Brain imaging and machine learning reveal uncoupled functional network for contextual threat memory in long sepsis. Sci Rep 2024; 14:27747. [PMID: 39533062 PMCID: PMC11557587 DOI: 10.1038/s41598-024-79259-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Accepted: 11/07/2024] [Indexed: 11/16/2024] Open
Abstract
Positron emission tomography (PET) utilizes radiotracers like [18F]fluorodeoxyglucose (FDG) to measure brain activity in health and disease. Performing behavioral tasks between the FDG injection and the PET scan allows the FDG signal to reflect task-related brain networks. Building on this principle, we introduce an approach called behavioral task-associated PET (beta-PET) consisting of two scans: the first after a mouse is familiarized with a conditioning chamber, and the second upon recall of contextual threat. Associative threat conditioning occurs between scans. Beta-PET focuses on brain regions encoding threat memory (e.g., amygdala, prefrontal cortex) and contextual aspects (e.g., hippocampus, subiculum, entorhinal cortex). Our results show that beta-PET identifies a biologically defined network encoding contextual threat memory and its uncoupling in a mouse model of long sepsis. Moreover, machine learning algorithms (linear logistic regression) and ordinal trends analysis demonstrate that beta-PET robustly predicts the behavioral defense response and its breakdown during long sepsis.
Collapse
Affiliation(s)
- Joshua J Strohl
- Laboratory of Immune and Neural Networks, Feinstein Institutes for Medical Research, 350 Community Drive, Manhasset, NY, 11030, USA
| | - Joseph Carrión
- Laboratory of Immune and Neural Networks, Feinstein Institutes for Medical Research, 350 Community Drive, Manhasset, NY, 11030, USA
| | - Patricio T Huerta
- Laboratory of Immune and Neural Networks, Feinstein Institutes for Medical Research, 350 Community Drive, Manhasset, NY, 11030, USA.
- Elmezzi Graduate School of Molecular Medicine at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA.
- Department of Molecular Medicine, Zucker School of Medicine at Hofstra/Northwell, 500 Hofstra Blvd, Hempstead, NY, 11549, USA.
| |
Collapse
|
10
|
Wang B, Ouyang J, Xing R, Jiang J, Ying M. A novel nomogram to predict the risk of requiring mechanical ventilation in patients with sepsis within 48 hours of admission: a retrospective analysis. PeerJ 2024; 12:e18500. [PMID: 39498290 PMCID: PMC11533908 DOI: 10.7717/peerj.18500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Accepted: 10/18/2024] [Indexed: 11/07/2024] Open
Abstract
Objective To establish a model that can predict the risk of requiring mechanical ventilation within 48 h after admission in patients with sepsis. Methods Data for patients with sepsis admitted to Dongyang People's Hospital from October 2011 to October 2023 were collected and divided into a modeling group and a validation group. Independent risk factors in the modeling group were analyzed, and a corresponding predictive nomogram was established. The model was evaluated for discriminative power (the area under the curve of the receiver operating characteristic curve, AUC), calibration degree (Hosmer-Lemeshow test), and clinical benefit (decision curve analysis, DCA). Models based on the Sequential Organ Failure Assessment (SOFA) scores, the National Early Warning Score (NEWS) scores and multiple machine learning methods were also established. Results The independent factors related to the risk of requiring mechanical ventilation in patients with sepsis within 48 h included lactic acid, pro-brain natriuretic peptide (PRO-BNP), and albumin levels, as well as prothrombin time, the presence of lung infection, and D-dimer levels. The AUC values of nomogram model in the modeling group and validation group were 0.820 and 0.837, respectively. The nomogram model had a good fit and clinical value. The AUC values of the models constructed using SOFA scores and NEWSs were significantly lower than those of the nomogram (P < 0.01). The AUC value of the integrated machine-learning model for the validation group was 0.849, comparable to that of the nomogram model (P = 0.791). Conclusion The established nomogram could effectively predict the risk of requiring mechanical ventilation within 48 h of admission by patients with sepsis. Thus, the model can be used for the treatment and management of sepsis.
Collapse
Affiliation(s)
- Bin Wang
- Emergency Department, Dongyang Hospital Affiliated to Wenzhou Medical University, Jinhua City, Zhejiang, China
| | - Jian Ouyang
- Emergency Department, Dongyang Hospital Affiliated to Wenzhou Medical University, Jinhua City, Zhejiang, China
| | - Rui Xing
- Haemaology Department, Dongyang Hospital Affiliated to Wenzhou Medical University, Jinhua City, Zhejiang, China
| | - Jiyuan Jiang
- Emergency Department, Dongyang Hospital Affiliated to Wenzhou Medical University, Jinhua City, Zhejiang, China
| | - Manzhen Ying
- Emergency Department, Dongyang Hospital Affiliated to Wenzhou Medical University, Jinhua City, Zhejiang, China
| |
Collapse
|
11
|
Stinehart KR, Hyer JM, Joshi S, Brummel NE. Healthcare Use and Expenditures in Rural Survivors of Hospitalization for Sepsis. Crit Care Med 2024; 52:1729-1738. [PMID: 39137035 DOI: 10.1097/ccm.0000000000006397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/15/2024]
Abstract
OBJECTIVES Sepsis survivors have greater healthcare use than those surviving hospitalizations for other reasons, yet factors associated with greater healthcare use in this population remain ill-defined. Rural Americans are older, have more chronic illnesses, and face unique barriers to healthcare access, which could affect postsepsis healthcare use. Therefore, we compared healthcare use and expenditures among rural and urban sepsis survivors. We hypothesized that rural survivors would have greater healthcare use and expenditures. DESIGN, SETTING, AND PATIENTS To test this hypothesis, we used data from 106,189 adult survivors of a sepsis hospitalization included in the IBM MarketScan Commercial Claims and Encounters database and Medicare Supplemental database between 2013 and 2018. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS We identified hospitalizations for severe sepsis and septic shock using the International Classification of Diseases , 9th Edition (ICD-9) or 1CD-10 codes. We used Metropolitan Statistical Area classifications to categorize rurality. We measured emergency department (ED) visits, inpatient hospitalizations, skilled nursing facility admissions, primary care visits, physical therapy visits, occupational therapy visits, and home healthcare visits for the year following sepsis hospitalizations. We calculated the total expenditures for each of these categories. We compared outcomes between rural and urban patients using multivariable regression and adjusted for covariates. After adjusting for age, sex, comorbidities, admission type, insurance type, U.S. Census Bureau region, employment status, and sepsis severity, those living in rural areas had 17% greater odds of having an ED visit (odds ratio [OR] 1.17; 95% CI, 1.13-1.22; p < 0.001), 9% lower odds of having a primary care visit (OR 0.91; 95% CI, 0.87-0.94; p < 0.001), and 12% lower odds of receiving home healthcare (OR 0.88; 95% CI, 0.84-0.93; p < 0.001). Despite higher levels of ED use and equivalent levels of hospital readmissions, expenditures in these areas were 14% (OR 0.86; 95% CI, 0.80-0.91; p < 0.001) and 9% (OR 0.91; 95% CI, 0.87-0.96; p < 0.001) lower among rural survivors, respectively, suggesting these services may be used for lower-acuity conditions. CONCLUSIONS In this large cohort study, we report important differences in healthcare use and expenditures between rural and urban sepsis survivors. Future research and policy work is needed to understand how best to optimize sepsis survivorship across the urban-rural continuum.
Collapse
Affiliation(s)
- Kyle R Stinehart
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, OH
- Department of Internal Medicine, Center for Health Outcomes in Medicine Scholarship and Service (HOMES), The Ohio State University Wexner Medical Center, Columbus, OH
| | - J Madison Hyer
- Center for Biostatistics, The Ohio State University College of Medicine, Columbus, OH
- Secondary Data Core, The Ohio State University Center for Clinical and Translational Science, Columbus, OH
| | - Shivam Joshi
- Center for Biostatistics, The Ohio State University College of Medicine, Columbus, OH
- Secondary Data Core, The Ohio State University Center for Clinical and Translational Science, Columbus, OH
| | - Nathan E Brummel
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, OH
- Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University College of Medicine, Columbus, OH
- Center for the Advancement of Team Science, Analytics, and Systems Thinking in Health Services and Implementation Science Research (CATALYST), The Ohio State University College of Medicine, Columbus, OH
| |
Collapse
|
12
|
Huerta PT, Strohl JJ, Carrión J. Brain imaging and machine learning reveal uncoupled functional network for contextual threat memory in long sepsis. RESEARCH SQUARE 2024:rs.3.rs-4870916. [PMID: 39483911 PMCID: PMC11527171 DOI: 10.21203/rs.3.rs-4870916/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2024]
Abstract
Positron emission tomography (PET) is a highly sensitive tool for studying physiology and metabolism through positron-emitting radionuclides that label molecular targets in the body with unparalleled specificity, without disturbing their biological function. Here, we introduce a small-animal technique called behavioral task-associated PET (beta-PET) consisting of two scans: the first after a mouse is familiarized with a conditioning chamber, and the second upon recall of contextual threat. Associative threat conditioning occurs between the scans. Beta-PET focuses on brain regions encoding threat memory (e.g., amygdala, prefrontal cortex) and contextual aspects (e.g., hippocampus, subiculum, entorhinal cortex). Our results show that beta-PET identifies a biologically defined functional network encoding contextual threat memory and its uncoupling in a mouse model of long sepsis. Moreover, machine learning algorithms (linear logistic regression) and ordinal trends analysis demonstrate that beta-PET robustly predicts the behavioral defense response and its breakdown during long sepsis.
Collapse
Affiliation(s)
| | | | - Joseph Carrión
- Feinstein Institutes for Medical Research, Northwell Health
| |
Collapse
|
13
|
LaBuzetta JN, Bongbong DN, Mlodzinski E, Sheth R, Trando A, Ibrahim N, Yip B, Malhotra A, Dinglas VD, Needham DM, Kamdar BB. Survivorship After Neurocritical Care: A Scoping Review of Outcomes Beyond Physical Status. Neurocrit Care 2024; 41:651-664. [PMID: 38622487 PMCID: PMC11377172 DOI: 10.1007/s12028-024-01965-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 02/21/2024] [Indexed: 04/17/2024]
Abstract
Following intensive care unit hospitalization, survivors of acute neurological injury often experience debilitating short-term and long-term impairments. Although the physical/motor impairments experienced by survivors of acute neurological injury have been described extensively, fewer studies have examined cognitive, mental health, health-related quality of life (HRQoL), and employment outcomes. This scoping review describes the publication landscape beyond physical and/or motor sequelae in neurocritical care survivors. Databases were searched for terms related to critical illness, intensive care, and outcomes from January 1970 to March 2022. English-language studies of critically ill adults with a primary neurological diagnosis were included if they reported on at least one outcome of interest: cognition, mental health, HRQoL or employment. Data extraction was performed in duplicate for prespecified variables related to study outcomes. Of 16,036 abstracts screened, 74 citations were identified for inclusion. The studies encompassed seven worldwide regions and eight neurocritical diagnosis categories. Publications reporting outcomes of interest increased from 3 before the year 2000 to 71 after. Follow-up time points included ≤ 1 (n = 15 [20%] citations), 3 (n = 28 [38%]), 6 (n = 28 [38%]), and 12 (n = 21 [28%]) months and 1 to 5 (n = 19 [26%]) and > 5 years (n = 8 [11%]), with 28 (38%) citations evaluating outcomes at multiple time points. Sixty-six assessment tools were used to evaluate the four outcomes of interest: 22 evaluating HRQoL (56 [76%] citations), 21 evaluating cognition (20 [27%] citations), 21 evaluating mental health (18 [24%] citations), and 2 evaluating employment (9 [12%] citations). This scoping review aimed to better understand the literature landscape regarding nonphysical outcomes in survivors of neurocritical care. Although a rising number of publications highlight growing awareness, future efforts are needed to improve study consistency and comparability and characterize outcomes in a disease-specific manner, including outlining of a minimum core outcomes set and associated assessment tools.
Collapse
Affiliation(s)
- Jamie Nicole LaBuzetta
- Division of Neurocritical Care, Department of Neurosciences, University of California, San Diego Health, 9444 Medical Center Dr., East Campus Office Building 3-028, La Jolla, CA, 92037-7740, USA.
| | - Dale N Bongbong
- Division of Neurocritical Care, Department of Neurosciences, University of California, San Diego Health, 9444 Medical Center Dr., East Campus Office Building 3-028, La Jolla, CA, 92037-7740, USA
| | - Eric Mlodzinski
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of California, San Diego Health, La Jolla, CA, USA
| | - Richa Sheth
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of California, San Diego Health, La Jolla, CA, USA
| | - Aaron Trando
- Division of Neurocritical Care, Department of Neurosciences, University of California, San Diego Health, 9444 Medical Center Dr., East Campus Office Building 3-028, La Jolla, CA, 92037-7740, USA
| | - Nicholas Ibrahim
- Division of Neurocritical Care, Department of Neurosciences, University of California, San Diego Health, 9444 Medical Center Dr., East Campus Office Building 3-028, La Jolla, CA, 92037-7740, USA
| | - Brandon Yip
- Division of Neurocritical Care, Department of Neurosciences, University of California, San Diego Health, 9444 Medical Center Dr., East Campus Office Building 3-028, La Jolla, CA, 92037-7740, USA
| | - Atul Malhotra
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of California, San Diego Health, La Jolla, CA, USA
| | - Victor D Dinglas
- Division of Pulmonary and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
- Outcomes After Critical Illness and Surgery (OACIS) Research Group, Johns Hopkins University, Baltimore, MD, USA
| | - Dale M Needham
- Division of Pulmonary and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
- Outcomes After Critical Illness and Surgery (OACIS) Research Group, Johns Hopkins University, Baltimore, MD, USA
- Department of Physical Medicine and Rehabilitation, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
| | - Biren B Kamdar
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of California, San Diego Health, La Jolla, CA, USA
| |
Collapse
|
14
|
Li H, Yu R, Zhou Q, Song J, Zhou Q, Ma W, Wang J, Hu Z, Yang Q, Chen K. TRENDS AND OUTCOMES IN SEPSIS HOSPITALIZATIONS WITH AND WITHOUT ACUTE KIDNEY INJURY: A NATIONWIDE INPATIENT ANALYSIS. Shock 2024; 62:470-479. [PMID: 38888575 DOI: 10.1097/shk.0000000000002386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/20/2024]
Abstract
ABSTRACT Background: Despite rapid advances in treatment, sepsis currently remains a major public health challenge worldwide. Over the past several years, there has been an increase in the clinical incidence of sepsis, as well as an increase in hospitalization rates, which bear the majority of the economic burden associated with sepsis. Sepsis is a public health burden due to the high fatality rates and accompanying morbidity. However, the sepsis-related mortality rates have fallen steadily over the years. One of the most common organs to fail in patients with sepsis is the kidney, and acute kidney injury (AKI) is associated with high mortality rates. This study's primary goal was to assess the impact of AKI on the evolution and outcome of hospitalization of patients with sepsis. Methods: Adults (≥18 years) hospitalized for sepsis in the United States between 2010 and 2019 were retrospectively analyzed using the nationally representative Nationwide Inpatient Sample database. Sepsis and AKI were defined using the codes of the International Classification of Diseases, Ninth Revision, Clinical Modification and the International Classification of Diseases, Tenth Revision, Clinical Modification. Results: Of the 4,258,360 outcomes, 3,946,048 met the inclusion criteria. The prevalence of AKI among sepsis inpatients increased from 39.10% in 2010 to 41% in 2019, but the impact of AKI on mortality declined over time, with in-hospital mortality from AKI among sepsis inpatients decreasing from 26.30% in 2010 to 16.30% in 2019. Hospitalizations linked to AKI were substantially more likely to involve infection sites such as the urinary tract, gastrointestinal tract, and endocarditis. Numerous pathogenic floras, including Escherichia coli , Staphylococcus aureus , Streptococcal , Enterococcus , and Pseudomonas , had greater rates among sepsis-related contacts with AKI. Furthermore, compared to hospitalization without comorbid AKI, the median total hospital charges and length of stay days for sepsis hospitalization with comorbid AKI were greater. Conclusion: With time, patients with sepsis have a higher frequency of AKI and a corresponding decline in mortality.
Collapse
Affiliation(s)
- Haibo Li
- Department of Anesthesiology, Chifeng Municipal Hospital, Chifeng, Inner Mongolia, China
| | - Ran Yu
- Department of Anesthesiology, Chifeng Clinical Medical College of Inner Mongolia Medical University, Chifeng, Inner Mongolia, China
| | - Qi Zhou
- Division of Orthopaedic Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Jiannan Song
- Department of Anesthesiology, Chifeng Municipal Hospital, Chifeng, Inner Mongolia, China
| | - Qi Zhou
- Department of Anesthesiology, Chifeng Municipal Hospital, Chifeng, Inner Mongolia, China
| | - Wanli Ma
- Department of Anesthesiology, Chifeng Municipal Hospital, Chifeng, Inner Mongolia, China
| | - Jian Wang
- Division of Orthopaedic Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Zhanfei Hu
- Department of Anesthesiology, Chifeng Municipal Hospital, Chifeng, Inner Mongolia, China
| | - Qinfeng Yang
- Division of Orthopaedic Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Keyuan Chen
- Division of Spine Surgery, Department of Orthopaedics, Guangzhou First People's Hospital, School of Medicine South China University of Technology, Guangzhou, Guangdong, China
| |
Collapse
|
15
|
Alaaeldin R, Mohyeldin RH, Sharata EE, Attya ME, Fathy M. Vincamine exerts hepato-protective activity during colon ligation puncture-induced sepsis by modulating oxidative stress, apoptosis, and TNFα/Nrf-2/Keap-1 signaling pathways. Sci Rep 2024; 14:19572. [PMID: 39174578 PMCID: PMC11341710 DOI: 10.1038/s41598-024-69729-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Accepted: 08/08/2024] [Indexed: 08/24/2024] Open
Abstract
Sepsis is a pathological and biochemical disorder induced by numerous infections, leading to critical illness and a high mortality rate worldwide. Vincamine is an indole alkaloid compound obtained from the leaves of Vinca minor. The present study aims to investigate the hepato-protective activity of vincamine during colon ligation puncture (CLP)-induced sepsis at the molecular level. Sepsis was induced using the CLP model. Liver function enzymes such as ALT and AST were analyzed. The hepatic antioxidant status (SOD and GSH), lipid peroxidation (MDA), the pro-inflammatory cytokines (TNFα, IL-6, and IL-1β), bax, bcl2, and cleaved caspase 3 proteins were estimated. Nrf-2 and Keap-1 protein expression was evaluated using western blotting. Histopathological investigation of liver tissues was also performed. CLP-induced sepsis led to liver injury through the elevation of ALT and AST liver enzymes. Oxidative stress was initiated during CLP via the suppression of hepatic GSH content and SOD activity and the elevation of MDA. The inflammatory condition was activated by the upregulation of TNFα, IL-6, IL-1β, and Keap-1 and the downregulation of Nrf-2 proteins. The apoptosis was initiated through the activation of bax and cleaved caspase 3 protein expression and inhibition of bcl2 protein expression. However, vincamine significantly improved the hepatic histological abnormalities and decreased liver enzymes (ALT and AST). It ameliorated oxidative stress, as evidenced by reducing the hepatic MDA content and increasing the SOD activity and GSH content. Moreover, vincamine reduced the hepatic content of TNFα, IL-6, IL-1β, and Keap-1 and increased Nrf-2 protein expression. Additionally, it upregulated bcl2 protein expression and downregulated bax and cleaved caspase 3 protein expression. Vincamine exhibited hepato-protective potential during CLP-induced sepsis via the cross-connection of antioxidant, anti-inflammatory, and anti-apoptotic activities by modulating TNFα/IL-6/IL-1β/Nrf-2/Keap-1 and regulating bax/bcl2/cleaved caspase 3 signaling pathways.
Collapse
Affiliation(s)
- Rania Alaaeldin
- Department of Biochemistry, Faculty of Pharmacy, Deraya University, Minia, 61111, Egypt
| | - Reham H Mohyeldin
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Deraya University, Minia, 61111, Egypt
| | - Ehab E Sharata
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Deraya University, Minia, 61111, Egypt
| | - Mina Ezzat Attya
- Department of Pathology, Faculty of Medicine, Minia University, Minia, 61519, Egypt
| | - Moustafa Fathy
- Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt.
| |
Collapse
|
16
|
Lim SY, Park JS, Cho YJ, Lee JH, Lee CT, Lee YJ. Association of baseline muscle mass with functional outcomes in intensive care unit survivors: A single-center retrospective cohort study in Korea. Medicine (Baltimore) 2024; 103:e39156. [PMID: 39121260 PMCID: PMC11315508 DOI: 10.1097/md.0000000000039156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 07/10/2024] [Indexed: 08/11/2024] Open
Abstract
In critical care settings, ultrasound (US) of the quadriceps muscle and Bioelectrical Impedance Analysis (BIA) are noninvasive and widely available tools to evaluate muscle mass. We studied whether baseline muscle mass affects physical function in intensive care unit (ICU) survivors after discharge. This retrospective review of a prospective cohort enrolled 30 patients admitted to the medical ICU between April 2016 and June 2018. On ICU admission, quadriceps muscle thickness and skeletal muscle mass were measured using US and BIA, respectively. Muscle strength and physical function were measured using handgrip dynamometry, the 6-min walk test, and the Barthel index questionnaire survey during every clinic visit at 1, 3, 6, and 12 months after hospital discharge. Skeletal muscle mass at ICU admission was statistically correlated with the 6-min walk distance (6MWD) and Barthel index score. The segmental lean mass of the right arm was also positively correlated with handgrip muscle strength at 6 months after discharge. Likewise, the correlation between quadriceps muscle thickness at ICU admission and 6MWD at 6 months after discharge was positive and statistically significant. Multivariate regression analysis showed that skeletal muscle mass was associated with a reduced 6MWD, but the length of ICU stay was not. The segmental lean mass of the right arm also showed a significant association with handgrip strength after discharge. Low muscle mass on ICU admission is associated with reduced muscle strength, causing impaired physical function after hospital discharge in ICU survivors.
Collapse
Affiliation(s)
- Sung Yoon Lim
- Department of Internal Medicine, Division of Pulmonology and Critical Care Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul, South Korea
| | - Jong Sun Park
- Department of Internal Medicine, Division of Pulmonology and Critical Care Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul, South Korea
| | - Young-Jae Cho
- Department of Internal Medicine, Division of Pulmonology and Critical Care Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul, South Korea
| | - Jae Ho Lee
- Department of Internal Medicine, Division of Pulmonology and Critical Care Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul, South Korea
| | - Choon-Taek Lee
- Department of Internal Medicine, Division of Pulmonology and Critical Care Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul, South Korea
| | - Yeon Joo Lee
- Department of Internal Medicine, Division of Pulmonology and Critical Care Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul, South Korea
| |
Collapse
|
17
|
Unal O, Erzurumlu Y, Asci H, Gunduru Acar B, Bedir M, Ozmen O. Nebivolol protects the liver against lipopolysaccharide-induced oxidative stress, inflammation, and endoplasmic reticulum-related apoptosis through Chop and Bip/GRP78 signaling. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:5899-5907. [PMID: 38353687 PMCID: PMC11329546 DOI: 10.1007/s00210-024-02990-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Accepted: 01/29/2024] [Indexed: 08/18/2024]
Abstract
This study aimed to examine the protective role of nebivolol (NEB) on liver tissue against the lipopolysaccharide (LPS)-induced sepsis model in rats by targeting endoplasmic reticulum (ER) stress-related binding immunoglobulin protein (Bip), CCAAT-enhancer-binding protein homologous protein (Chop) signaling pathways. Four groups, each comprising eight rats, were established: control, LPS, LPS + NEB, and NEB. Biochemical analyses included total oxidant status (TOS), serum aspartate transaminase (AST), and alanine aminotransferase (ALT) levels. Additionally, genetic assessments involved Chop and Bip/GRP78 mRNA expression levels, while histopathological examinations were conducted. Immunohistochemistry was used to determine interleukin-1 beta (IL-1 β) and caspase-3 levels. The LPS group exhibited significantly higher AST, ALT, oxidative stress index, and TOS levels compared to the control group. Moreover, the LPS group demonstrated markedly increased Chop and Bip/GRP78 mRNA expression compared to the control group. Immunohistochemical analysis of the LPS group revealed significant upregulation in IL-1β and caspase-3 expressions compared to the control group. Additionally, the LPS group showed significant hyperemia, mild hemorrhage, and inflammatory cell infiltrations. Comparatively, the LPS+NEB group exhibited a reversal of these alterations when compared to the LPS group. Collectively, our findings, suggest that NEB holds promise as a treatment in conditions where oxidative damage, inflammation, and ER stress-related apoptosis play significant roles in the pathogenesis.
Collapse
Affiliation(s)
- Onur Unal
- Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey.
| | - Yalcin Erzurumlu
- Department of Biochemistry, Faculty of Pharmacy, Suleyman Demirel University, Isparta, Turkey
| | - Halil Asci
- Department of Pharmacology, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey
| | - Berivan Gunduru Acar
- Department of Pharmacology, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey
| | - Mehmet Bedir
- Department of Biochemistry, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey
| | - Ozlem Ozmen
- Department of Pathology, Faculty of Veterinary Medicine, Burdur Mehmet Akif Ersoy University, Burdur, Turkey
| |
Collapse
|
18
|
May CN, Ow CP, Pustovit RV, Lane DJ, Jufar AH, Trask-Marino A, Peiris RM, Gunn A, Booth LC, Plummer MP, Bellomo R, Lankadeva YR. Reversal of cerebral ischaemia and hypoxia and of sickness behaviour by megadose sodium ascorbate in ovine Gram-negative sepsis. Br J Anaesth 2024; 133:316-325. [PMID: 38960833 DOI: 10.1016/j.bja.2024.04.058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 04/08/2024] [Accepted: 04/25/2024] [Indexed: 07/05/2024] Open
Abstract
BACKGROUND The mechanisms by which megadose sodium ascorbate improves clinical status in experimental sepsis is unclear. We determined its effects on cerebral perfusion, oxygenation, and temperature, and plasma levels of inflammatory biomarkers, nitrates, nitrites, and ascorbate in ovine Gram-negative sepsis. METHODS Sepsis was induced by i.v. infusion of live Escherichia coli for 31 h in unanaesthetised Merino ewes instrumented with a combination sensor in the frontal cerebral cortex to measure tissue perfusion, oxygenation, and temperature. Fluid resuscitation at 23 h was followed by i.v. megadose sodium ascorbate (0.5 g kg-1 over 30 min+0.5 g kg-1 h-1 for 6.5 h) or vehicle (n=6 per group). Norepinephrine was titrated to restore mean arterial pressure (MAP) to 70-80 mm Hg. RESULTS At 23 h of sepsis, MAP (mean [sem]: 85 [2] to 64 [2] mm Hg) and plasma ascorbate (27 [2] to 15 [1] μM) decreased (both P<0.001). Cerebral ischaemia (901 [58] to 396 [40] units), hypoxia (34 [1] to 19 [3] mm Hg), and hyperthermia (39.5 [0.1]°C to 40.8 [0.1]°C) (all P<0.001) developed, accompanied by malaise and lethargy. Sodium ascorbate restored cerebral perfusion (703 [121] units], oxygenation (30 [2] mm Hg), temperature (39.2 [0.1]°C) (all PTreatment<0.05), and the behavioural state to normal. Sodium ascorbate slightly reduced the sepsis-induced increase in interleukin-6, returned VEGF-A to normal (both PGroupxTime<0.01), and increased plasma ascorbate (20 000 [300] μM; PGroup<0.001). The effects of sodium ascorbate were not reproduced by equimolar sodium bicarbonate. CONCLUSIONS Megadose sodium ascorbate rapidly reversed sepsis-induced cerebral ischaemia, hypoxia, hyperthermia, and sickness behaviour. These effects were not reproduced by an equimolar sodium load.
Collapse
Affiliation(s)
- Clive N May
- Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia; Department of Critical Care, Melbourne Medical School, University of Melbourne, Melbourne, VIC, Australia.
| | - Connie P Ow
- Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia
| | - Ruslan V Pustovit
- Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia
| | - Darius J Lane
- Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia; Melbourne Dementia Research Centre, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia
| | - Alemayehu H Jufar
- Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia
| | - Anton Trask-Marino
- Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia
| | - Rachel M Peiris
- Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia
| | - Adam Gunn
- Melbourne Dementia Research Centre, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia
| | - Lindsea C Booth
- Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia
| | - Mark P Plummer
- Department of Intensive Care, Royal Melbourne Hospital, Melbourne, VIC, Australia; Department of Intensive Care, Royal Adelaide Hospital, Adelaide, VIC, Australia
| | - Rinaldo Bellomo
- Department of Critical Care, Melbourne Medical School, University of Melbourne, Melbourne, VIC, Australia; Department of Intensive Care, Royal Melbourne Hospital, Melbourne, VIC, Australia; Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, VIC, Australia; Department of Intensive Care, Austin Hospital, Melbourne, VIC, Australia
| | - Yugeesh R Lankadeva
- Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia; Department of Critical Care, Melbourne Medical School, University of Melbourne, Melbourne, VIC, Australia
| |
Collapse
|
19
|
La Via L, Sangiorgio G, Stefani S, Marino A, Nunnari G, Cocuzza S, La Mantia I, Cacopardo B, Stracquadanio S, Spampinato S, Lavalle S, Maniaci A. The Global Burden of Sepsis and Septic Shock. EPIDEMIOLOGIA 2024; 5:456-478. [PMID: 39189251 PMCID: PMC11348270 DOI: 10.3390/epidemiologia5030032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 07/07/2024] [Accepted: 07/18/2024] [Indexed: 08/28/2024] Open
Abstract
A dysregulated host response to infection causes organ dysfunction in sepsis and septic shock, two potentially fatal diseases. They continue to be major worldwide health burdens with high rates of morbidity and mortality despite advancements in medical care. The goal of this thorough review was to present a thorough summary of the current body of knowledge about the prevalence of sepsis and septic shock worldwide. Using widely used computerized databases, a comprehensive search of the literature was carried out, and relevant studies were chosen in accordance with predetermined inclusion and exclusion criteria. A narrative technique was used to synthesize the data that were retrieved. The review's conclusions show how widely different locations and nations differ in terms of sepsis and septic shock's incidence, prevalence, and fatality rates. Compared to high-income countries (HICs), low- and middle-income countries (LMICs) are disproportionately burdened more heavily. We talk about risk factors, comorbidities, and difficulties in clinical management and diagnosis in a range of healthcare settings. The review highlights the need for more research, enhanced awareness, and context-specific interventions in order to successfully address the global burden of sepsis and septic shock.
Collapse
Affiliation(s)
- Luigi La Via
- Department of Anaesthesia and Intensive Care, University Hospital Policlinico “G. Rodolico-San Marco”, 24046 Catania, Italy
| | - Giuseppe Sangiorgio
- Department of Biomedical and Biotechnological Sciences, University of Catania, Via Santa Sofia 97, 95123 Catania, Italy; (G.S.); (S.S.); (S.S.)
| | - Stefania Stefani
- Department of Biomedical and Biotechnological Sciences, University of Catania, Via Santa Sofia 97, 95123 Catania, Italy; (G.S.); (S.S.); (S.S.)
| | - Andrea Marino
- Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, ARNAS Garibaldi Hospital, University of Catania, 95123 Catania, Italy; (A.M.); (G.N.); (B.C.); (S.S.)
| | - Giuseppe Nunnari
- Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, ARNAS Garibaldi Hospital, University of Catania, 95123 Catania, Italy; (A.M.); (G.N.); (B.C.); (S.S.)
| | - Salvatore Cocuzza
- Department of Medical, Surgical Sciences and Advanced Technologies “GF Ingrassia” ENT Section, University of Catania, 95123 Catania, Italy; (S.C.); (I.L.M.)
| | - Ignazio La Mantia
- Department of Medical, Surgical Sciences and Advanced Technologies “GF Ingrassia” ENT Section, University of Catania, 95123 Catania, Italy; (S.C.); (I.L.M.)
| | - Bruno Cacopardo
- Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, ARNAS Garibaldi Hospital, University of Catania, 95123 Catania, Italy; (A.M.); (G.N.); (B.C.); (S.S.)
| | - Stefano Stracquadanio
- Department of Biomedical and Biotechnological Sciences, University of Catania, Via Santa Sofia 97, 95123 Catania, Italy; (G.S.); (S.S.); (S.S.)
| | - Serena Spampinato
- Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, ARNAS Garibaldi Hospital, University of Catania, 95123 Catania, Italy; (A.M.); (G.N.); (B.C.); (S.S.)
| | - Salvatore Lavalle
- Department of Medicine and Surgery, University of Enna “Kore”, 94100 Enna, Italy; (S.L.); (A.M.)
| | - Antonino Maniaci
- Department of Medicine and Surgery, University of Enna “Kore”, 94100 Enna, Italy; (S.L.); (A.M.)
| |
Collapse
|
20
|
Bodechtel U, Koch T, Heubner L, Spieth P, Rößler I, Mehrholz J. Health-related quality of life and participation after inpatient rehabilitation of sepsis survivors with severe sequelae: a cohort study. J Rehabil Med 2024; 56:jrm18670. [PMID: 38956963 PMCID: PMC11247512 DOI: 10.2340/jrm.v56.18670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2023] [Accepted: 05/30/2024] [Indexed: 07/04/2024] Open
Abstract
OBJECTIVE To describe health-related quality of life and participation after rehabilitation of severely affected sepsis survivors. DESIGN Cohort study. SUBJECTS/PATIENTS Patients with severe sequelae after sepsis treated in a multidisciplinary rehabilitation pathway were included. METHODS Patient characteristics at the time of diagnosis, and the outcome 3 months after discharge from rehabilitation are described. At that time, health-related quality of life, social participation, and the rate of living at home were measured. RESULTS Of the 498 patients enrolled, 100 severely impaired patients were transferred for a multidisciplinary rehabilitation approach. Fifty-five of them were followed up at 3 months. Descriptive and inference statistics showed that 69% were living at home with or without care. Health-related quality of life and participation scores were 0.64 ± 0.32 for the EQ-5D utility index and 54.98 ± 24.97 for the Reintegration of Normal Living Index. A multivariate regression model explaining health-related quality of life at 3 months included age, lower limb strength, and walking ability during rehabilitation (r2 = 0.5511). Participation at 3 months was explained by age, body mass index, lower limb strength, and duration of tracheal intubation (r2 = 0.6229). CONCLUSION Patients who have experienced serious sepsis with severe sequelae can achieve a moderate level of quality of life and participation within a multidisciplinary pathway.
Collapse
Affiliation(s)
| | - Thea Koch
- Klinik für Anästhesiologie und Intensivtherapie, Medizinische Fakultät 'Carl Gustav Carus', Technische Universität Dresden, Dresden, Germany
| | - Lars Heubner
- Klinik für Anästhesiologie und Intensivtherapie, Medizinische Fakultät 'Carl Gustav Carus', Technische Universität Dresden, Dresden, Germany
| | - Peter Spieth
- Klinik für Anästhesiologie und Intensivtherapie, Medizinische Fakultät 'Carl Gustav Carus', Technische Universität Dresden, Dresden, Germany
| | - Ines Rößler
- Klinik Bavaria in Kreischa, Kreischa, Germany
| | - Jan Mehrholz
- Wissenschaftliches Institut, Private Europäische Medizinische Akademie der Klinik Bavaria in Kreischa, Kreischa, Germany; Department of Public Health, Medizinische Fakultät 'Carl Gustav Carus', Technische Universität Dresden, Germany.
| |
Collapse
|
21
|
Magnin M, Gavet M, Ngo TT, Louzier V, Victoni T, Ayoub JY, Allaouchiche B, Bonnet-Garin JM, Junot S. A multimodal tissue perfusion measurement approach for the evaluation of the effect of pimobendan, an inodilator, in a porcine sepsis model. Microvasc Res 2024; 154:104687. [PMID: 38614155 DOI: 10.1016/j.mvr.2024.104687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 04/03/2024] [Accepted: 04/10/2024] [Indexed: 04/15/2024]
Abstract
Sepsis is associated with hypoperfusion and organ failure. The aims of the study were: 1) to assess the effect of pimobendan on macrocirculation and perfusion and 2) to describe a multimodal approach to the assessment of perfusion in sepsis and compare the evolution of the perfusion parameters. Eighteen anaesthetized female piglets were equipped for macrocirculation monitoring. Sepsis was induced by an infusion of Pseudomonas aeruginosa. After the occurrence of hypotension, animals were resuscitated. Nine pigs received pimobendan at the start of resuscitation maneuvers, the others received saline. Tissue perfusion was assessed using temperature gradients measured with infrared thermography (TG = core temperature - tarsus temperature), urethral perfusion index (uPI) derived from photoplethysmography and sublingual microcirculation (Sidestream dark field imaging device): De Backer score (DBs), proportion of perfused vessels (PPV), microvascular flow index (MFI) and heterogeneity index (HI). Arterial lactate and ScvO2 were also measured. Pimobendan did not improve tissue perfusion nor macrocirculation. It did not allow a reduction in the amount of noradrenaline and fluids administered. Sepsis was associated with tissue perfusion disorders: there were a significant decrease in uPI, PPV and ScvO2 and a significant rise in TG. TG could significantly predict an increase in lactate. Resuscitation was associated with a significant increase in uPI, DBs, MFI, lactate and ScvO2. There were fair correlations between the different perfusion parameters. In this model, pimobendan did not show any benefit. The multimodal approach allowed the detection of tissue perfusion alteration but only temperature gradients predicted the increase in lactatemia.
Collapse
Affiliation(s)
- Mathieu Magnin
- Université de Lyon, UR APCSe Agressions Pulmonaires et Circulatoires dans le Sepsis, VetAgro Sup, 1 avenue Bourgelat, F-69280 Marcy l'Etoile, France; Université de Lyon, Vetagro Sup, Unité de Physiologie, Pharmacodynamie et Thérapeutique, 1 avenue Bourgelat, F-69280 Marcy l'Etoile, France.
| | - Morgane Gavet
- Université de Lyon, VetAgro Sup, Service d'Anesthésie, 1 avenue Bourgelat, F-69280 Marcy l'Etoile, France.
| | - Thien-Tam Ngo
- Université de Lyon, UR APCSe Agressions Pulmonaires et Circulatoires dans le Sepsis, VetAgro Sup, 1 avenue Bourgelat, F-69280 Marcy l'Etoile, France; Université de Lyon, Vetagro Sup, Unité de Physiologie, Pharmacodynamie et Thérapeutique, 1 avenue Bourgelat, F-69280 Marcy l'Etoile, France
| | - Vanessa Louzier
- Université de Lyon, UR APCSe Agressions Pulmonaires et Circulatoires dans le Sepsis, VetAgro Sup, 1 avenue Bourgelat, F-69280 Marcy l'Etoile, France; Université de Lyon, Vetagro Sup, Unité de Physiologie, Pharmacodynamie et Thérapeutique, 1 avenue Bourgelat, F-69280 Marcy l'Etoile, France.
| | - Tatiana Victoni
- Université de Lyon, UR APCSe Agressions Pulmonaires et Circulatoires dans le Sepsis, VetAgro Sup, 1 avenue Bourgelat, F-69280 Marcy l'Etoile, France; Université de Lyon, Vetagro Sup, Unité de Physiologie, Pharmacodynamie et Thérapeutique, 1 avenue Bourgelat, F-69280 Marcy l'Etoile, France.
| | - Jean Yves Ayoub
- Université de Lyon, UR APCSe Agressions Pulmonaires et Circulatoires dans le Sepsis, VetAgro Sup, 1 avenue Bourgelat, F-69280 Marcy l'Etoile, France; Université de Lyon, Vetagro Sup, Unité de Physiologie, Pharmacodynamie et Thérapeutique, 1 avenue Bourgelat, F-69280 Marcy l'Etoile, France.
| | - Bernard Allaouchiche
- Université de Lyon, UR APCSe Agressions Pulmonaires et Circulatoires dans le Sepsis, VetAgro Sup, 1 avenue Bourgelat, F-69280 Marcy l'Etoile, France; Université de Lyon, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Réanimation Médicale, 165 Chemin du Grand Revoyet, F-69310 Pierre-Bénite, France
| | - Jeanne-Marie Bonnet-Garin
- Université de Lyon, UR APCSe Agressions Pulmonaires et Circulatoires dans le Sepsis, VetAgro Sup, 1 avenue Bourgelat, F-69280 Marcy l'Etoile, France; Université de Lyon, Vetagro Sup, Unité de Physiologie, Pharmacodynamie et Thérapeutique, 1 avenue Bourgelat, F-69280 Marcy l'Etoile, France.
| | - Stéphane Junot
- Université de Lyon, UR APCSe Agressions Pulmonaires et Circulatoires dans le Sepsis, VetAgro Sup, 1 avenue Bourgelat, F-69280 Marcy l'Etoile, France; Université de Lyon, Vetagro Sup, Unité de Physiologie, Pharmacodynamie et Thérapeutique, 1 avenue Bourgelat, F-69280 Marcy l'Etoile, France; Université de Lyon, VetAgro Sup, Service d'Anesthésie, 1 avenue Bourgelat, F-69280 Marcy l'Etoile, France.
| |
Collapse
|
22
|
Song F, Li Q, Cui J, Wang J, Xiao S, Yu B, Sun Y, Song W, Wu L, Zhou Y. Exploring the gut microbiota-hippocampus-metabolites axis dysregulation in sepsis mice. Front Microbiol 2024; 15:1302907. [PMID: 38827158 PMCID: PMC11140095 DOI: 10.3389/fmicb.2024.1302907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 03/18/2024] [Indexed: 06/04/2024] Open
Abstract
Background Sepsis is commonly associated with a sudden impairment of brain function, thus leading to significant rates of illness and mortality. The objective of this research was to integrate microbiome and metabolome to reveal the mechanism of microbiota-hippocampus-metabolites axis dysfunction in a mouse model of sepsis. Methods A mouse model of sepsis was established via cecal ligation and puncture. The potential associations between the composition of the gut microbiota and metabolites in the hippocampus of mice with sepsis were investigated by combining 16S ribosomal RNA gene sequencing and ultra-high-performance liquid chromatography tandem mass spectrometry. Results A total of 140 differential metabolites were identified in the hippocampal tissues of mice with sepsis when compared to those of control mice. These differential metabolites in mice with sepsis were not only associated with autophagy and serotonergic synapse, but also involved in the metabolism and synthesis of numerous amino acids. At the phylum level, the abundance of Bacteroidota was increased, while that of Firmicutes (Bacillota) was decreased in mice with sepsis. At the genus level, the abundance of Alistipes was increased, while that of Lachnospiraceae_NK4A136_group was decreased in mice with sepsis. The Firmicutes (Bacillota)/Bacteroidota (F/B) ratio was decreased in mice with sepsis when compared to that of control mice. Furthermore, the F/B ratio was positively correlated with 5'-methylthioadenosine, PC (18:3(9Z,12Z,15Z)/18:0) and curdione, and negatively correlated with indoxylsulfuric acid, corticosterone, kynurenine and ornithine. Conclusion Analysis revealed a reduction in the F/B ratio in mice with sepsis, thus contributing to the disturbance of 5'-methylthioadenosine, curdione, PC (18:3(9Z,12Z,15Z)/18:0), corticosterone, ornithine, indoxylsulfuric acid and kynurenine; eventually, these changes led to hippocampus dysfunction. Our findings provide a new direction for the management of sepsis-induced hippocampus dysfunction.
Collapse
Affiliation(s)
- Fangqiang Song
- Department of Critical Care Medicine, Tengzhou Central People’s Hospital, Tengzhou, China
| | - Qinglun Li
- Department of Critical Care Medicine, Tengzhou Central People’s Hospital, Tengzhou, China
| | - Jiyao Cui
- Department of Critical Care Medicine, Tengzhou Central People’s Hospital, Tengzhou, China
| | - Jianhua Wang
- Translational Pharmaceutical Laboratory, Jining NO. 1 People’s Hospital, Jining, China
| | - Shuai Xiao
- Department of Critical Care Medicine, Tengzhou Central People’s Hospital, Tengzhou, China
| | - Bo Yu
- Department of Critical Care Medicine, Tengzhou Central People’s Hospital, Tengzhou, China
| | - Yanqi Sun
- Department of Critical Care Medicine, Tengzhou Central People’s Hospital, Tengzhou, China
| | - Wenke Song
- Department of Critical Care Medicine, Tengzhou Central People’s Hospital, Tengzhou, China
| | - Linlin Wu
- Department of Oncology, Tengzhou Central People’s Hospital, Tengzhou, China
| | - Yongqin Zhou
- Department of Critical Care Medicine, Tengzhou Central People’s Hospital, Tengzhou, China
| |
Collapse
|
23
|
Jain S, Murphy TE, Falvey JR, Leo-Summers L, O’Leary JR, Zang E, Gill TM, Krumholz HM, Ferrante LE. Social Determinants of Health and Delivery of Rehabilitation to Older Adults During ICU Hospitalization. JAMA Netw Open 2024; 7:e2410713. [PMID: 38728030 PMCID: PMC11087837 DOI: 10.1001/jamanetworkopen.2024.10713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 03/09/2024] [Indexed: 05/13/2024] Open
Abstract
Importance Older adults with socioeconomic disadvantage develop a greater burden of disability after critical illness than those without socioeconomic disadvantage. The delivery of in-hospital rehabilitation that can mitigate functional decline may be influenced by social determinants of health (SDOH). Whether rehabilitation delivery differs by SDOH during critical illness hospitalization is not known. Objective To evaluate whether SDOH are associated with the delivery of skilled rehabilitation during critical illness hospitalization among older adults. Design, Setting, and Participants This cohort study used data from the National Health and Aging Trends Study linked with Medicare claims (2011-2018). Participants included older adults hospitalized with a stay in the intensive care unit (ICU). Data were analyzed from August 2022 to September 2023. Exposures Dual eligibility for Medicare and Medicaid, education, income, limited English proficiency (LEP), and rural residence. Main Outcome and Measures The primary outcome was delivery of physical therapy (PT) and/or occupational therapy (OT) during ICU hospitalization, characterized as any in-hospital PT or OT and rate of in-hospital PT or OT, calculated as total number of units divided by length of stay. Results In the sample of 1618 ICU hospitalizations (median [IQR] patient age, 81.0 [75.0-86.0] years; 842 [52.0%] female), 371 hospitalizations (22.9%) were among patients with dual Medicare and Medicaid eligibility, 523 hospitalizations (32.6%) were among patients with less than high school education, 320 hospitalizations (19.8%) were for patients with rural residence, and 56 hospitalizations (3.5%) were among patients with LEP. A total of 1076 hospitalized patients (68.5%) received any PT or OT, with a mean rate of 0.94 (95% CI, 0.86-1.02) units/d. After adjustment for age, sex, prehospitalization disability, mechanical ventilation, and organ dysfunction, factors associated with lower odds of receipt of PT or OT included dual Medicare and Medicaid eligibility (adjusted odds ratio, 0.70 [95% CI, 0.50-0.97]) and rural residence (adjusted odds ratio, 0.65 [95% CI, 0.48-0.87]). LEP was associated with a lower rate of PT or OT (adjusted rate ratio, 0.55 [95% CI, 0.32-0.94]). Conclusions and Relevance These findings highlight the need to consider SDOH in efforts to promote rehabilitation delivery during ICU hospitalization and to investigate factors underlying inequities in this practice.
Collapse
Affiliation(s)
- Snigdha Jain
- Section of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
| | - Terrence E. Murphy
- Department of Public Health Sciences, Pennsylvania State University, State College
| | - Jason R. Falvey
- Department of Physical Therapy and Rehabilitation Science, University of Maryland School of Medicine, Baltimore
| | | | - John R. O’Leary
- Program on Aging, Yale School of Medicine, New Haven, Connecticut
| | - Emma Zang
- Department of Sociology, Yale University, New Haven, Connecticut
| | - Thomas M. Gill
- Program on Aging, Yale School of Medicine, New Haven, Connecticut
| | - Harlan M. Krumholz
- Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut
| | - Lauren E. Ferrante
- Section of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
| |
Collapse
|
24
|
Fang Y, Xiong B, Shang X, Yang F, Yin Y, Sun Z, Wu X, Zhang J, Liu Y. Triglyceride-glucose index predicts sepsis-associated acute kidney injury and length of stay in sepsis: A MIMIC-IV cohort study. Heliyon 2024; 10:e29257. [PMID: 38617935 PMCID: PMC11015450 DOI: 10.1016/j.heliyon.2024.e29257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 03/23/2024] [Accepted: 04/03/2024] [Indexed: 04/16/2024] Open
Abstract
Background Inflammation and stress response may be related to the occurrence of sepsis-associated acute kidney injury (SA-AKI) in patients with sepsis.Insulin resistance (IR) is closely related to the stress response, inflammatory response, immune response and severity of critical diseases. We assume that the triglyceride-glucose (TyG) index, an alternative indicator for IR, is associated with the occurrence of SA-AKI in patients with sepsis. Methods Data were obtained from The Medical Information Mart for Intensive Care-IV(MIMIC-IV) database in this retrospective cohort study. Univariate and multivariate logistic regression analysis and multivariate restricted cubic spline(RCS) regression were conducted to evaluate the association between TyG index and SA-AKI, length of stay (LOS). Subgroup and sensitivity analyses were performed to verify the robustness of the results. Results The study ultimately included data from 1426 patients with sepsis, predominantly of white ethnicity (59.2%) and male sex (56.4%), with an SA-AKI incidence rate of 78.5%. A significant linear association was observed between the TyG index and SA-AKI (OR, 1.40; 95% confidence interval(CI) [1.14-1.73]). Additionally, the TyG index demonstrated a significant correlation with the length of stay (LOS) in both the hospital (β, 1.79; 95% CI [0.80-2.77]) and the intensive care unit (ICU) (β, 1.30; 95% CI [0.80-1.79]). Subgroup and sensitivity analyses confirmed the robustness of these associations. Conclusion This study revealed a strong association between the TyG index and both SA-AKI and length of stay in patients with sepsis. These findings suggest that the TyG index is a potential predictor of SA-AKI and the length of hospitalization in sepsis cases, broadening its application in this context. However, further research is required to confirm whether interventions targeting the TyG index can genuinely enhance the clinical outcomes of patients with sepsis.
Collapse
Affiliation(s)
| | | | | | | | - Yuehao Yin
- Department of Anesthesiology, Shanghai Cancer Centre, Fudan University, Shanghai, 200032, China
| | - Zhirong Sun
- Department of Anesthesiology, Shanghai Cancer Centre, Fudan University, Shanghai, 200032, China
| | - Xin Wu
- Department of Anesthesiology, Shanghai Cancer Centre, Fudan University, Shanghai, 200032, China
| | - Jun Zhang
- Department of Anesthesiology, Shanghai Cancer Centre, Fudan University, Shanghai, 200032, China
| | - Yi Liu
- Corresponding author. Department of Anesthesiology, Shanghai Cancer Centre, Fudan University, No. 270 Dong an Road, Shanghai, 200032, China.
| |
Collapse
|
25
|
Ferguson CE, Lambell KJ, Ridley EJ, Goh GS, Hodgson CL, Holland AE, Harrold M, Chan T, Tipping CJ. Muscularity of older trauma patients at intensive care unit admission, association with functional outcomes, and relationship with frailty: A retrospective observational study. Aust Crit Care 2024; 37:205-211. [PMID: 37532620 DOI: 10.1016/j.aucc.2023.06.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 06/06/2023] [Accepted: 06/21/2023] [Indexed: 08/04/2023] Open
Abstract
BACKGROUND Older individuals are at an increased risk of delayed recovery following a traumatic injury. Measurement of muscularity and frailty at hospital admission may aid with prognostication and risk stratification. OBJECTIVE This study aimed to describe muscularity at intensive care unit (ICU) admission in patients admitted following trauma and assess the relationship between muscularity and clinical, long-term functional outcomes and frailty at ICU admission. METHODS This retrospective study utilised data from a prospective observational study investigating frailty in patients aged ≥50 years, admitted to the ICU following trauma. Patients were eligible if they had a Computed Tomography (CT) scan including the third lumbar vertebra at ICU admission. Specialist software was used to quantify CT-derived skeletal muscle cross-sectional area. Muscularity status was classified as normal or low using published sex-specific cut-points. Demographic data, frailty, clinical, and long-term functional outcomes (Glasgow Outcome Scale-Extended and EQ-5DL-5L Visual analogue scale and utility score) were extracted from the original study. RESULTS One hundred patients were screened; 71 patients had a CT scan on admission with 66 scans suitable for muscle assessment. Patients with low muscularity (n = 25, 38%) were older and had a higher Acute Physiology and Chronic Health Evaluation II score and lower body mass index than patients with normal muscularity. Low muscularity was associated with frailty at admission (32% vs 5%, p = 0.005) but not with long term outcomes at 6 or 12 months. As a continuous variable, lower muscle cross-sectional area was associated with a poorer outcome on the Glasgow Outcome Scale-Extended at 6 months (mean [standard deviation]: 150 [43] and 180 [44], respectively; p = 0.014), no association was observed after adjustment for age p = 0.43). CONCLUSION In a population of older adults hospitalised following trauma, low muscularity at ICU admission was prevalent. Low muscularity was associated with frailty but not long-term functional outcomes. Larger studies are warranted to better understand the relationship between muscularity and long-term functional outcomes.
Collapse
Affiliation(s)
- Clare E Ferguson
- Dietetics and Nutrition Department, The Alfred Hospital, Melbourne, Victoria, Australia; Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne 3004, Australia.
| | - Kate J Lambell
- Dietetics and Nutrition Department, The Alfred Hospital, Melbourne, Victoria, Australia.
| | - Emma J Ridley
- Dietetics and Nutrition Department, The Alfred Hospital, Melbourne, Victoria, Australia; Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne 3004, Australia.
| | - Gerard S Goh
- Department of Radiology, The Alfred, Melbourne, Victoria, Australia; Department of Surgery, Central Clinical School, Monash University, Melbourne, Australia; National Trauma Research Institute, Melbourne, Australia.
| | - Carol L Hodgson
- Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne 3004, Australia; Division of Clinical Trial and Cohort Studies, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; Department of Critical Care, University of Melbourne, Melbourne, Victoria, Australia; The George Institute for Global Health; Department of Physiotherapy, The Alfred Hospital, Melbourne, Victoria, Australia.
| | - Anne E Holland
- Department of Physiotherapy, The Alfred Hospital, Melbourne, Victoria, Australia; Respiratory Research @ Alfred, Department of Immunology & Pathology, The Central Clinical School, Monash University, Australia.
| | - Meg Harrold
- Curtin School of Allied Health, Curtin University, Perth, WA, Australia.
| | - Terry Chan
- Department of Physiotherapy, The Alfred Hospital, Melbourne, Victoria, Australia.
| | - Claire J Tipping
- Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne 3004, Australia; Department of Physiotherapy, The Alfred Hospital, Melbourne, Victoria, Australia.
| |
Collapse
|
26
|
Kattlun F, Hertel E, Geis C, Scherag A, Wickel J, Finke K. Persistent neurocognitive deficits in cognitively impaired survivors of sepsis are explained by reductions in working memory capacity. Front Psychol 2024; 15:1321145. [PMID: 38449763 PMCID: PMC10915060 DOI: 10.3389/fpsyg.2024.1321145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 02/08/2024] [Indexed: 03/08/2024] Open
Abstract
Introduction Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Mounting evidence suggests that many cognitively impaired sepsis survivors show long-term neurocognitive deficits in neuropsychological tasks. To date, the underlying mechanisms of these deficits are insufficiently understood. Based on previous evaluations we hypothesized that visual attention and working memory may be affected in a sample of cognitively impaired sepsis survivors. Methods We utilized psychophysical whole-and partial-report paradigms based on the computational theory of visual attention (TVA) to determine (i) whether sepsis survivors show changes in basic parameters of visual attention and working memory, (ii) whether the affected parameters are related to neuropsychological test results in a standard battery in sepsis survivors and matched healthy control participants, (iii) whether between-group differences in these basic parameters of visual attention could account for underperformance of sepsis survivors in neuropsychological tests when adjusting for potentially relevant clinical variables. Results We showed that, in sepsis survivors, the maximum number of elements consciously maintained in an instant, i.e. the working memory storage capacity K, is reduced (sepsis survivors: M = 3.0; healthy controls: M = 3.4). Moreover, K explained variance in neurocognitive outcomes -17% in attentional and 16 % in executive functions - in a standard neuropsychological battery. The association remained stable when adjusting for clinical variables. Discussion Thus, in our sample of cognitively impaired sepsis survivors, a reduction in working memory capacity seems to be a critical determinant of the neurocognitive sequelae. It should be the subject of future work on mechanisms but may also serve as surrogate outcome measure in interventional studies.
Collapse
Affiliation(s)
- Fabian Kattlun
- Department of Neurology, Jena University Hospital - Friedrich Schiller University, Jena, Germany
- Center for Sepsis Control and Care, Jena University Hospital - Friedrich Schiller University, Jena, Germany
| | - Elizabeth Hertel
- Department of Neurology, Jena University Hospital - Friedrich Schiller University, Jena, Germany
- Center for Sepsis Control and Care, Jena University Hospital - Friedrich Schiller University, Jena, Germany
| | - Christian Geis
- Center for Sepsis Control and Care, Jena University Hospital - Friedrich Schiller University, Jena, Germany
- Section Translational Neuroimmunology, Department of Neurology, Jena University Hospital - Friedrich Schiller University, Jena, Germany
| | - André Scherag
- Center for Sepsis Control and Care, Jena University Hospital - Friedrich Schiller University, Jena, Germany
- Institute of Medical Statistics, Computer and Data Sciences, Jena University Hospital - Friedrich Schiller University, Jena, Germany
| | - Jonathan Wickel
- Center for Sepsis Control and Care, Jena University Hospital - Friedrich Schiller University, Jena, Germany
- Section Translational Neuroimmunology, Department of Neurology, Jena University Hospital - Friedrich Schiller University, Jena, Germany
| | - Kathrin Finke
- Department of Neurology, Jena University Hospital - Friedrich Schiller University, Jena, Germany
- Center for Sepsis Control and Care, Jena University Hospital - Friedrich Schiller University, Jena, Germany
| |
Collapse
|
27
|
Schade Skov C, Østervang C, Brabrand M, Lassen AT, Nielsen DS. How do sepsis survivors experience life after sepsis? A Danish qualitative study exploring factors of importance. BMJ Open 2024; 14:e081558. [PMID: 38355189 PMCID: PMC10868268 DOI: 10.1136/bmjopen-2023-081558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 01/31/2024] [Indexed: 02/16/2024] Open
Abstract
OBJECTIVE Sepsis is a condition associated with high mortality and morbidity, and survivors often experience physical and psychological decline. Previous research has primarily focused on sepsis survivors discharged from the intensive care unit (ICU). We aimed to explore and understand the consequences of sepsis experienced by sepsis survivors in general. DESIGN A qualitative study inspired by a phenomenological hermeneutical approach was conducted. Data were analysed using systematic text condensation. SETTING Patients with sepsis were identified on admission to the emergency department and invited to an interview 3 months after discharge. PARTICIPANTS Sixteen sepsis survivors were purposively sampled and interviewed. Among these survivors, one patient was admitted to the ICU. RESULTS Three main themes were derived from the analysis: new roles in life, cognitive impairment and anxiety. Although many survivors described a physical decline, they experienced psychological and cognitive impairments after sepsis as the most influential factors in daily life. The survivors frequently experienced fatigue, withdrawals from social activities and anxiety. CONCLUSION Sepsis survivors' experiences appeared to overlap regardless of ICU admission or treatment at the general ward. Identifying patients with sepsis-related decline is important to understand and support overall patient processes and necessary in meeting specific needs of these patients after hospital discharge.
Collapse
Affiliation(s)
- Camilla Schade Skov
- Department of Emergency Medicine, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Christina Østervang
- Department of Emergency Medicine, Odense University Hospital, Odense, Denmark
| | - Mikkel Brabrand
- Department of Emergency Medicine, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Annmarie Touborg Lassen
- Department of Emergency Medicine, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Dorthe Susanne Nielsen
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Geriatric Medicine, Odense University Hospital, Odense, Denmark
| |
Collapse
|
28
|
Roseau-Vincenti A, Forestier E, Lanoix JP, Ricard C, Carret MC, Caraux-Paz P, Paccalin M, Gavazzi G, Roubaud-Baudron C. Empirical antibiotic therapy modalities for Enterobacteriaceae bloodstream infections in older patients and their impact on mortality: a multicentre retrospective study. Infection 2024; 52:155-163. [PMID: 37608043 DOI: 10.1007/s15010-023-02073-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Accepted: 07/01/2023] [Indexed: 08/24/2023]
Abstract
PURPOSE Enterobacteriaceae (EB) bloodstream infections (BSI) are frequent and serious in older patients. Physicians are faced with the dilemma of prescribing early appropriate empirical antibiotics to limit the risk of death, and sparing broad-spectrum antibiotic prescription. The aim of the study was to assess the rate of appropriate empirical antibiotics prescription to treat EB BSI in older patients and its impact on survival. METHODS This study conducted in 49 centres enrolled retrospectively up to the 10 last consecutive patients aged 75 years and over and treated for EB BSI. Factors related to in-hospital death were investigated using logistic regression. RESULTS Among the 487 enrolled patients (mean age 86 ± 5.9 years), 70% had at least one risk factor of being infected by third-generation cephalosporins (3GC)-resistant strain; however, only 13.8% of EB strains were resistant to 3GC. An empirical antimicrobial treatment was initiated for 418 patients (85.8%), and for 86% (n = 360/418) of them, it was considered appropriate. In-hospital mortality was 12.7% (n = 62) and was related to the severity of infection (OR 3.17, CI 95% 1.75-5.75), while a urinary portal of entry was protective (OR 0.34, CI 95% 0.19-0.60). Neither the absence of nor inappropriate empirical antibiotics prescription was associated with increased mortality. CONCLUSION While patients enrolled in this study were at risk of being infected by multidrug-resistant bacteria, yet mainly treated with 3GC, empirical antibiotics prescription was appropriate in most cases and did not influence mortality.
Collapse
Affiliation(s)
| | | | | | - Cécile Ricard
- Epidémiologiste/statisticienne indépendante, Annecy, France
| | | | - Pauline Caraux-Paz
- Maladies infectieuses CH Intercommunal Villeneuve-Saint-Georges, Villeneuve-Saint-Georges, France
| | | | - Gaëtan Gavazzi
- Clinique universitaire de médecine gériatrique, CHU Grenoble-Alpes, Grenoble, France
| | - Claire Roubaud-Baudron
- CHU Bordeaux, Pôle de gérontologie clinique, 33000, Bordeaux, France.
- Univ. Bordeaux, BRIC Bordeaux Institute of Oncology INSERM UMR 1312, 33000, Bordeaux, France.
| |
Collapse
|
29
|
Wang Q, Sun J, Liu X, Ping Y, Feng C, Liu F, Feng X. Comparison of risk prediction models for the progression of pelvic inflammatory disease patients to sepsis: Cox regression model and machine learning model. Heliyon 2024; 10:e23148. [PMID: 38163183 PMCID: PMC10754857 DOI: 10.1016/j.heliyon.2023.e23148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 11/27/2023] [Accepted: 11/27/2023] [Indexed: 01/03/2024] Open
Abstract
Introduction The present study presents the development and validation of a clinical prediction model using random survival forest (RSF) and stepwise Cox regression, aiming to predict the probability of pelvic inflammatory disease (PID) progressing to sepsis. Methods A retrospective cohort study was conducted, gathering clinical data of patients diagnosed with PID between 2008 and 2019 from the Medical Information Mart for Intensive Care (MIMIC)-IV database. Patients who met the Sepsis 3.0 diagnostic criteria were selected, with sepsis as the outcome. Univariate Cox regression and stepwise Cox regression were used to screen variables for constructing a nomogram. Moreover, an RSF model was created using machine learning algorithms. To verify the model's performance, a calibration curve, decision curve analysis (DCA), and receiver operating characteristic (ROC) curve were utilized. Furthermore, the capabilities of the two models for estimating the incidence of sepsis in PID patients within 3 and 7 days were compared. Results A total of 1064 PID patients were included, of whom 54 had progressed to sepsis. The established nomogram highlighted dialysis, reduced platelet (PLT) counts, history of pneumonia, medication of glucocorticoids, and increased leukocyte counts as significant predictive factors. The areas under the curve (AUCs) of the nomogram for prediction of PID progression to sepsis at 3-day and 7-day (3-/7-day) in the training set and the validation set were 0.886/0.863 and 0.824/0.726, respectively, and the C-index of the model was 0.8905. The RSF displayed excellent performance, with AUCs of 0.939/0.919 and 0.712/0.571 for 3-/7-day risk prediction in the training set and validation set, respectively. Conclusion The nomogram accurately predicted the incidence of sepsis in PID patients, and relevant risk factors were identified. While the RSF model outperformed the Cox regression models in predicting sepsis incidence, its performance exhibited some instability. On the other hand, the Cox regression-based nomogram displayed stable performance and improved interpretability, thereby supporting clinical decision-making in PID treatment.
Collapse
Affiliation(s)
- Qingyi Wang
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Jianing Sun
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Xiaofang Liu
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Yunlu Ping
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Chuwen Feng
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Fanglei Liu
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Xiaoling Feng
- Department of Gynecology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
| |
Collapse
|
30
|
Shibata M, Miyamoto K, Shima N, Nakashima T, Fukushima J, Yamada S, Kimoto S, Inoue S. The effect of ICU diary on psychiatric symptoms after ICU discharge among adult critically ill patients: A prospective comparative study. Acute Med Surg 2024; 11:e70026. [PMID: 39610395 PMCID: PMC11603429 DOI: 10.1002/ams2.70026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 11/05/2024] [Accepted: 11/17/2024] [Indexed: 11/30/2024] Open
Abstract
Aim Psychiatric problems are common in critically ill patients after discharge from an intensive care unit (ICU). The effect of intensive care unit (ICU) diaries on psychiatric symptoms after ICU discharge was investigated in this prospective study. Methods Enrolled were critically ill adult patients who were emergently admitted to an ICU and expected to stay for at least 2 days. These patients received ICU diaries filled out by healthcare professionals and family members. Comparison was made with a historical cohort from a previous trial conducted in the same ICU but without ICU diaries. The primary outcome was the presence of significant post-traumatic stress disorder (PTSD) symptoms 3 months after ICU discharge. Secondary outcomes included significant symptoms of anxiety and depression. Results Among 61 patients with ICU diaries, questionnaires were sent to 44 patients 3 months after ICU discharge; 29 patients responded and were analyzed (ICU diary group). Seventy-four patients from a historical cohort were used as a control group. The proportion of patients with significant PTSD symptoms was 19% in the ICU diary group and 16% in the control group (adjusted odds ratio [aOR] [95% confidence interval: 95% CI]: 0.98 [0.26-3.70]). For anxiety and depression, the proportions were 25% and 29% in the ICU diary group, and 38% and 45% in the control group (aOR [95% CI]: 0.46 [0.15-1.38] for anxiety, aOR [95% CI] 0.40 [0.14-1.16] for depression). Conclusion ICU diaries were not associated with a reduced incidence of PTSD symptoms 3 months after ICU discharge.
Collapse
Affiliation(s)
- Mami Shibata
- Department of Emergency and Critical Care MedicineWakayama Medical UniversityWakayama CityJapan
| | - Kyohei Miyamoto
- Department of Emergency and Critical Care MedicineWakayama Medical UniversityWakayama CityJapan
| | - Nozomu Shima
- Department of Emergency and Critical Care MedicineWakayama Medical UniversityWakayama CityJapan
| | - Tsuyoshi Nakashima
- Department of Emergency and Critical Care MedicineWakayama Medical UniversityWakayama CityJapan
| | - Junichi Fukushima
- Department of Emergency and Critical Care MedicineWakayama Medical UniversityWakayama CityJapan
| | - Shinichi Yamada
- Department of NeuropsychiatryWakayama Medical UniversityWakayama CityJapan
| | - Sohei Kimoto
- Department of NeuropsychiatryWakayama Medical UniversityWakayama CityJapan
| | - Shigeaki Inoue
- Department of Emergency and Critical Care MedicineWakayama Medical UniversityWakayama CityJapan
| |
Collapse
|
31
|
Latronico N, Rasulo FA, Eikermann M, Piva S. Illness Weakness, Polyneuropathy and Myopathy: Diagnosis, treatment, and long-term outcomes. Crit Care 2023; 27:439. [PMID: 37957759 PMCID: PMC10644573 DOI: 10.1186/s13054-023-04676-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 10/04/2023] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND Severe weakness associated with critical illness (CIW) is common. This narrative review summarizes the latest scientific insights and proposes a guide for clinicians to optimize the diagnosis and management of the CIW during the various stages of the disease from the ICU to the community stage. MAIN BODY CIW arises as diffuse, symmetrical weakness after ICU admission, which is an important differentiating factor from other diseases causing non-symmetrical muscle weakness or paralysis. In patients with adequate cognitive function, CIW can be easily diagnosed at the bedside using manual muscle testing, which should be routinely conducted until ICU discharge. In patients with delirium or coma or those with prolonged, severe weakness, specific neurophysiological investigations and, in selected cases, muscle biopsy are recommended. With these exams, CIW can be differentiated into critical illness polyneuropathy or myopathy, which often coexist. On the general ward, CIW is seen in patients with prolonged previous ICU treatment, or in those developing a new sepsis. Respiratory muscle weakness can cause neuromuscular respiratory failure, which needs prompt recognition and rapid treatment to avoid life-threatening situations. Active rehabilitation should be reassessed and tailored to the new patient's condition to reduce the risk of disease progression. CIW is associated with long-term physical, cognitive and mental impairments, which emphasizes the need for a multidisciplinary model of care. Follow-up clinics for patients surviving critical illness may serve this purpose by providing direct clinical support to patients, managing referrals to other specialists and general practitioners, and serving as a platform for research to describe the natural history of post-intensive care syndrome and to identify new therapeutic interventions. This surveillance should include an assessment of the activities of daily living, mood, and functional mobility. Finally, nutritional status should be longitudinally assessed in all ICU survivors and incorporated into a patient-centered nutritional approach guided by a dietician. CONCLUSIONS Early ICU mobilization combined with the best evidence-based ICU practices can effectively reduce short-term weakness. Multi-professional collaborations are needed to guarantee a multi-dimensional evaluation and unitary community care programs for survivors of critical illnesses.
Collapse
Affiliation(s)
- Nicola Latronico
- Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.
- Department of Emergency, ASST Spedali Civili University Hospital, Piazzale Ospedali Civili, 1, 25123, Brescia, Italy.
- "Alessandra Bono" Interdepartmental University Research Center On Long-Term Outcome (LOTO) in Critical Illness Survivors, University of Brescia, Brescia, Italy.
| | - Frank A Rasulo
- Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
- Department of Emergency, ASST Spedali Civili University Hospital, Piazzale Ospedali Civili, 1, 25123, Brescia, Italy
- "Alessandra Bono" Interdepartmental University Research Center On Long-Term Outcome (LOTO) in Critical Illness Survivors, University of Brescia, Brescia, Italy
| | - Matthias Eikermann
- Department of Anesthesiology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Simone Piva
- Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
- Department of Emergency, ASST Spedali Civili University Hospital, Piazzale Ospedali Civili, 1, 25123, Brescia, Italy
| |
Collapse
|
32
|
Chen Y, Yang L, Li X. Advances in Mesenchymal stem cells regulating macrophage polarization and treatment of sepsis-induced liver injury. Front Immunol 2023; 14:1238972. [PMID: 37954578 PMCID: PMC10634316 DOI: 10.3389/fimmu.2023.1238972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Accepted: 10/17/2023] [Indexed: 11/14/2023] Open
Abstract
Sepsis is a syndrome of dysregulated host response caused by infection, which leads to life-threatening organ dysfunction. It is a familiar reason of death in critically ill patients. Liver injury frequently occurs in septic patients, yet the development of targeted and effective treatment strategies remains a pressing challenge. Macrophages are essential parts of immunity system. M1 macrophages drive inflammation, whereas M2 macrophages possess anti-inflammatory properties and contribute to tissue repair processes. Mesenchymal stem cells (MSCs), known for their remarkable attributes including homing capabilities, immunomodulation, anti-inflammatory effects, and tissue regeneration potential, hold promise in enhancing the prognosis of sepsis-induced liver injury by harmonizing the delicate balance of M1/M2 macrophage polarization. This review discusses the mechanisms by which MSCs regulate macrophage polarization, alongside the signaling pathways involved, providing an idea for innovative directions in the treatment of sepsis-induced liver injury.
Collapse
Affiliation(s)
- Yuhao Chen
- Department of Emergency Medicine, West China Second Hospital of Sichuan University, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Sichuan, China
| | - Lihong Yang
- Department of Emergency Medicine, West China Second Hospital of Sichuan University, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Sichuan, China
| | - Xihong Li
- Department of Emergency Medicine, West China Second Hospital of Sichuan University, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Sichuan, China
| |
Collapse
|
33
|
Hu J, Xie S, Zhang H, Wang X, Meng B, Zhang L. Microglial Activation: Key Players in Sepsis-Associated Encephalopathy. Brain Sci 2023; 13:1453. [PMID: 37891821 PMCID: PMC10605398 DOI: 10.3390/brainsci13101453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Revised: 10/03/2023] [Accepted: 10/11/2023] [Indexed: 10/29/2023] Open
Abstract
Sepsis-associated encephalopathy (SAE) is a common brain dysfunction, which results in severe cognitive and neurological sequelae and an increased mortality rate in patients with sepsis. Depending on the stimulus, microglia (resident macrophages in the brain that are involved in SAE pathology and physiology) can adopt two polarization states (M1/M2), corresponding to altered microglial morphology, gene expression, and function. We systematically described the pathogenesis, morphology, function, and phenotype of microglial activation in SAE and demonstrated that microglia are closely related to SAE occurrence and development, and concomitant cognitive impairment. Finally, some potential therapeutic approaches that can prime microglia and neuroinflammation toward the beneficial restorative microglial phenotype in SAE were outlined.
Collapse
Affiliation(s)
- Jiyun Hu
- Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
- Hunan Provincial Clinical Research Center for Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Shucai Xie
- Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
- Hunan Provincial Clinical Research Center for Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Haisong Zhang
- Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
- Hunan Provincial Clinical Research Center for Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Xinrun Wang
- Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
- Hunan Provincial Clinical Research Center for Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Binbin Meng
- Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
- Hunan Provincial Clinical Research Center for Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Lina Zhang
- Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
- Hunan Provincial Clinical Research Center for Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| |
Collapse
|
34
|
Teixeira RMP, Oliveira JC, de Andrade MAB, Pinheiro FGDMS, Vieira RDCA, Santana-Santos E. Are patient volume and care level in teaching hospitals variables affecting clinical outcomes in adult intensive care units? EINSTEIN-SAO PAULO 2023; 21:eAO0406. [PMID: 37820201 PMCID: PMC10519666 DOI: 10.31744/einstein_journal/2023ao0406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Accepted: 02/07/2023] [Indexed: 10/13/2023] Open
Abstract
Teixeira et al. showed that patients admitted to the intensive care unit of a teaching hospital in a non-metropolitan region needed more support, had worse prognostic indices, and had a higher nursing workload in the first 24 hours of admission. In addition, worse outcomes, including mortality, need for dialysis, pressure injury, infection, prolonged mechanical ventilation, and prolonged hospital stay, were observed in the teaching hospital. Worse outcomes were more prevalent in the teaching hospital. Understanding the importance of teaching hospitals to implement well-established care protocols is critical. OBJECTIVE To compare the clinical outcomes of patients admitted to the intensive care unit of teaching (HI) and nonteaching (without an academic affiliation; H2) hospitals. METHODS In this prospective cohort study, adult patients hospitalized between August 2018 and July 2019, with a minimum length of stay of 24 hours in the intensive care unit, were included. Patients with no essential information in their medical records to evaluate the study outcomes were excluded. Resuslts: Overall, 219 patients participated in this study. The clinical and demographic characteristics of patients in H1 and H2 were similar. The most prevalent clinical outcomes were death, need for dialysis, pressure injury, length of hospital stay, mechanical ventilation >48 hours, and infection, all of which were more prevalent in the teaching hospital. CONCLUSION Worse outcomes were more prevalent in the teaching hospital. There was no difference between the institutions concerning the survival rate of patients as a function of length of hospital stay; however, a difference was observed in intensive care unit admissions.
Collapse
Affiliation(s)
| | - Jussiely Cunha Oliveira
- Universidade Federal de SergipeSão CristovãoSEBrazil Universidade Federal de Sergipe, São Cristovão, SE, Brazil.
| | | | | | | | - Eduesley Santana-Santos
- Universidade Federal de SergipeSão CristovãoSEBrazil Universidade Federal de Sergipe, São Cristovão, SE, Brazil.
| |
Collapse
|
35
|
Kurematsu K, Ikematsu Y. Quality of Life of Sepsis Survivors. Crit Care Med 2023; 51:1339-1349. [PMID: 37314395 DOI: 10.1097/ccm.0000000000005944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
OBJECTIVE To determine the differences between the quality of life for sepsis and nonsepsis survivors, factors affecting the quality of life for sepsis survivors, and their changes over time. DESIGN A prospective longitudinal study with a quantitative comparative design. SETTING A university hospital in the greater Tokyo area of Japan. PATIENTS The study included 41 and 40 patients in the sepsis and nonsepsis groups, respectively. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Health-related quality of life (HRQOL), independence in activities of daily living (ADL), stress levels, and spirituality were compared between the sepsis and nonsepsis groups at ICU discharge, hospital discharge, and 1 month after discharge. Comparison of HRQOL between the sepsis and nonsepsis groups showed significantly low HRQOL in the sepsis group compared with the nonsepsis group at ICU discharge and hospital discharge. Factors such as stress levels and spirituality affected the HRQOL in the nonsepsis group at ICU discharge. At discharge, stress and spirituality affected HRQOL in both the sepsis and nonsepsis groups. One month after discharge, ADL, stress, and spirituality affected HRQOL in both the sepsis and nonsepsis groups. In terms of changes over time, HRQOL at ICU discharge in the sepsis group was significantly lower than at discharge and 1 month after discharge. The two-way analyses of variance showed no interactions between the groups and time regarding HRQOL. CONCLUSIONS HRQOL of sepsis survivors was significantly lower than that of nonsepsis survivors. ADL and stress influenced HRQOL. The study suggests the importance of ADL training and stress alleviation during the ICU stay.
Collapse
Affiliation(s)
- Kumiko Kurematsu
- Department of Nursing, Nagoya University Graduate School of Medicine, Aichi, Japan
- Department of Nursing, Kitasato University Hospital, Kanagawa, Japan
| | | |
Collapse
|
36
|
van der Slikke EC, Beumeler LFE, Holmqvist M, Linder A, Mankowski RT, Bouma HR. Understanding Post-Sepsis Syndrome: How Can Clinicians Help? Infect Drug Resist 2023; 16:6493-6511. [PMID: 37795206 PMCID: PMC10546999 DOI: 10.2147/idr.s390947] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Accepted: 09/21/2023] [Indexed: 10/06/2023] Open
Abstract
Sepsis is a global health challenge, with over 49 million cases annually. Recent medical advancements have increased in-hospital survival rates to approximately 80%, but the escalating incidence of sepsis, owing to an ageing population, rise in chronic diseases, and antibiotic resistance, have also increased the number of sepsis survivors. Subsequently, there is a growing prevalence of "post-sepsis syndrome" (PSS). This syndrome includes long-term physical, medical, cognitive, and psychological issues after recovering from sepsis. PSS puts survivors at risk for hospital readmission and is associated with a reduction in health- and life span, both at short and long term, after hospital discharge. Comprehensive understanding of PSS symptoms and causative factors is vital for developing optimal care for sepsis survivors, a task of prime importance for clinicians. This review aims to elucidate our current knowledge of PSS and its relevance in enhancing post-sepsis care provided by clinicians.
Collapse
Affiliation(s)
- Elisabeth C van der Slikke
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, 9713GZ, the Netherlands
| | - Lise F E Beumeler
- Department of Intensive Care, Medical Centre Leeuwarden, Leeuwarden, 8934AD, the Netherlands
- Department of Sustainable Health, Campus Fryslân, University of Groningen, Groningen, 8911 CE, the Netherlands
| | - Madlene Holmqvist
- Department of Infection Medicine, Skåne University Hospital Lund, Lund, 221 84, Sweden
| | - Adam Linder
- Department of Infection Medicine, Skåne University Hospital Lund, Lund, 221 84, Sweden
| | - Robert T Mankowski
- Department of Physiology and Aging, University of Florida, Gainesville, FL, 32610, USA
| | - Hjalmar R Bouma
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, 9713GZ, the Netherlands
- Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, 9713GZ, the Netherlands
| |
Collapse
|
37
|
Sieminski M, Szaruta-Raflesz K, Szypenbejl J, Krzyzaniak K. Potential Neuroprotective Role of Melatonin in Sepsis-Associated Encephalopathy Due to Its Scavenging and Anti-Oxidative Properties. Antioxidants (Basel) 2023; 12:1786. [PMID: 37760089 PMCID: PMC10525116 DOI: 10.3390/antiox12091786] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 09/08/2023] [Accepted: 09/20/2023] [Indexed: 09/29/2023] Open
Abstract
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The brain is one of the organs involved in sepsis, and sepsis-induced brain injury manifests as sepsis-associated encephalopathy (SAE). SAE may be present in up to 70% of septic patients. SAE has a very wide spectrum of clinical symptoms, ranging from mild behavioral changes through cognitive disorders to disorders of consciousness and coma. The presence of SAE increases mortality in the population of septic patients and may lead to chronic cognitive dysfunction in sepsis survivors. Therefore, therapeutic interventions with neuroprotective effects in sepsis are needed. Melatonin, a neurohormone responsible for the control of circadian rhythms, exerts many beneficial physiological effects. Its anti-inflammatory and antioxidant properties are well described. It is considered a potential therapeutic factor in sepsis, with positive results from studies on animal models and with encouraging results from the first human clinical trials. With its antioxidant and anti-inflammatory potential, it may also exert a neuroprotective effect in sepsis-associated encephalopathy. The review presents data on melatonin as a potential drug in SAE in the wider context of the pathophysiology of SAE and the specific actions of the pineal neurohormone.
Collapse
Affiliation(s)
- Mariusz Sieminski
- Department of Emergency Medicine, Medical University of Gdansk, 80-214 Gdansk, Poland; (K.S.-R.); (K.K.)
| | | | - Jacek Szypenbejl
- Department of Emergency Medicine, Medical University of Gdansk, 80-214 Gdansk, Poland; (K.S.-R.); (K.K.)
| | | |
Collapse
|
38
|
Ning XL, Shao M. Analysis of prognostic factors in patients with emergency sepsis. World J Clin Cases 2023; 11:5903-5909. [PMID: 37727482 PMCID: PMC10506019 DOI: 10.12998/wjcc.v11.i25.5903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 07/21/2023] [Accepted: 08/07/2023] [Indexed: 09/01/2023] Open
Abstract
BACKGROUND Emergency sepsis is a common and serious infectious disease, and its prognosis is influenced by a number of factors. AIM To analyse the factors influencing the prognosis of patients with emergency sepsis in order to provide a basis for individualised patient treatment and care. By retrospectively analysing the clinical data collected, we conducted a comprehensive analysis of factors such as age, gender, underlying disease, etiology and site of infection, inflammatory indicators, multi-organ failure, cardiovascular function, therapeutic measures, immune status and severity of infection. METHODS Data collection: Clinical data were collected from patients diagnosed with acute sepsis, including basic information, laboratory findings, medical history and treatment options. Variable selection: Variables associated with prognosis were selected, including age, gender, underlying disease, etiology and site of infection, inflammatory indicators, multi-organ failure, cardiovascular function, treatment measures, immune status and severity of infection. Data analysis: The data collected are analysed using appropriate statistical methods such as multiple regression analysis and survival analysis. The impact of each factor on prognosis was assessed according to prognostic indicators, such as survival, length of stay and complication rates. RESULTS Descriptive statistics: Descriptive statistics were performed on the data collected from the patients, including their basic characteristics and clinical presentation. CONCLUSION Type 2 diabetes mellitus were independent factors affecting the prognosis of patients with sepsis.
Collapse
Affiliation(s)
- Xian-Li Ning
- Department of Emergency, Anqing Municipal Hospital, Anqing 246000, Anhui Province, China
| | - Min Shao
- Department of Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei 230031, Anhui Province, China
| |
Collapse
|
39
|
Aubert L. [Rules of good practice for the elderly]. SOINS. GERONTOLOGIE 2023; 28:13-18. [PMID: 37716775 DOI: 10.1016/j.sger.2023.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/18/2023]
Abstract
The treatment of infectious diseases in geriatric medicine is a complex subject. Diagnosis is often difficult, as is the correct indication for antibiotic therapy. To combat antibiotic resistance, we need to limit unnecessary antibiotic prescriptions and prevent the onset of bacterial infections, notably through vaccination.
Collapse
Affiliation(s)
- Lucie Aubert
- Université Paris-Saclay, Site Ambroise-Paré, Boulogne-Billancourt, France.
| |
Collapse
|
40
|
Karlic KJ, Clouse TL, Hogan CK, Garland A, Seelye S, Sussman JB, Prescott HC. Comparison of Administrative versus Electronic Health Record-based Methods for Identifying Sepsis Hospitalizations. Ann Am Thorac Soc 2023; 20:1309-1315. [PMID: 37163757 DOI: 10.1513/annalsats.202302-105oc] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 05/10/2023] [Indexed: 05/12/2023] Open
Abstract
Rationale: Despite the importance of sepsis surveillance, no optimal approach for identifying sepsis hospitalizations exists. The Centers for Disease Control and Prevention Adult Sepsis Event Definition (CDC-ASE) is an electronic medical record-based algorithm that yields more stable estimates over time than diagnostic coding-based approaches but may still result in misclassification. Objectives: We sought to assess three approaches to identifying sepsis hospitalizations, including a modified CDC-ASE. Methods: This cross-sectional study included patients in the Veterans Affairs Ann Arbor Healthcare System admitted via the emergency department (February 2021 to February 2022) with at least one episode of acute organ dysfunction within 48 hours of emergency department presentation. Patients were assessed for community-onset sepsis using three methods: 1) explicit diagnosis codes, 2) the CDC-ASE, and 3) a modified CDC-ASE. The modified CDC-ASE required at least two systemic inflammatory response syndrome criteria instead of blood culture collection and had a more sensitive definition of respiratory dysfunction. Each method was compared with a reference standard of physician adjudication via medical record review. Patients were considered to have sepsis if they had at least one episode of acute organ dysfunction graded as "definitely" or "probably" infection related on physician review. Results: Of 821 eligible hospitalizations, 449 were selected for physician review. Of these, 98 (21.8%) were classified as sepsis by medical record review, 103 (22.9%) by the CDC-ASE, 132 (29.4%) by the modified CDC-ASE, and 37 (8.2%) by diagnostic codes. Accuracy was similar across the three methods of interest (80.6% for the CDC-ASE, 79.6% for the modified CDC-ADE, and 84.2% for diagnostic codes), but sensitivity and specificity varied. The CDC-ASE algorithm had sensitivity of 58.2% (95% confidence interval [CI], 47.2-68.1%) and specificity of 86.9% (95% CI, 82.9-90.2%). The modified CDC-ASE algorithm had greater sensitivity (69.4% [95% CI, 59.3-78.3%]) but lower specificity (81.8% [95% CI, 77.3-85.7%]). Diagnostic codes had lower sensitivity (32.7% [95% CI, 23.5-42.9%]) but greater specificity (98.6% [95% CI, 96.7-99.55%]). Conclusions: There are several approaches to identifying sepsis hospitalizations for surveillance that have acceptable accuracy. These approaches yield varying sensitivity and specificity, so investigators should carefully consider the test characteristics of each method before determining an appropriate method for their intended use.
Collapse
Affiliation(s)
- Kevin J Karlic
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
| | - Tori L Clouse
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
| | - Cainnear K Hogan
- Veterans Affairs Center for Clinical Management Research, Ann Arbor, Michigan; and
| | - Allan Garland
- Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Sarah Seelye
- Veterans Affairs Center for Clinical Management Research, Ann Arbor, Michigan; and
| | - Jeremy B Sussman
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
- Veterans Affairs Center for Clinical Management Research, Ann Arbor, Michigan; and
| | - Hallie C Prescott
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
- Veterans Affairs Center for Clinical Management Research, Ann Arbor, Michigan; and
| |
Collapse
|
41
|
Hendel MK, Rizzuto D, Grande G, Calderón-Larrañaga A, Laukka EJ, Fratiglioni L, Vetrano DL. Impact of Pneumonia on Cognitive Aging: A Longitudinal Propensity-Matched Cohort Study. J Gerontol A Biol Sci Med Sci 2023; 78:1453-1460. [PMID: 36526613 PMCID: PMC10395566 DOI: 10.1093/gerona/glac253] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Indexed: 08/03/2023] Open
Abstract
BACKGROUND Acute clinical events, such as pneumonia, may impact physical functionality but their effect on cognition and the possible duration of this effect remains to be quantified. This study investigated the impact of pneumonia on cognitive trajectories and dementia development in older people. METHODS Data were obtained from 60+ years old individuals, who were assessed from 2001 to 2018 in the population-based SNAC-K study (Sweden). Participants were eligible if they were not institutionalized, had no dementia, and did not experience pneumonia 5 years prior to baseline (N = 2 063). A propensity score was derived to match 1:3 participants hospitalized with a diagnosis of pneumonia (N = 178), to nonexposed participants (N = 534). Mixed linear models were used to model cognitive decline. The hazard of dementia, clinically diagnosed by physicians following Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV, was estimated using Cox regression models. RESULTS We found a transient impact of pneumonia on cognitive decline in the first 2.5 years (B = -0.94, 95% confidence interval [CI] -1.75, -0.15). The hazard ratio (HR) for dementia was not statistically significantly increased in pneumonia participants (HR = 1.17, 95%CI 0.82, 1.66). CONCLUSIONS The transient impact of pneumonia on cognitive function suggests an increased need of health care for patients after a pneumonia-related hospitalization and reinforces the relevance of pneumonia prevention.
Collapse
Affiliation(s)
- Merle K Hendel
- Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden
| | - Debora Rizzuto
- Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden
- Gerontology Research Center, Stockholm, Sweden
| | - Giulia Grande
- Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden
| | - Amaia Calderón-Larrañaga
- Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden
- Gerontology Research Center, Stockholm, Sweden
| | - Erika J Laukka
- Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden
- Gerontology Research Center, Stockholm, Sweden
| | - Laura Fratiglioni
- Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden
- Gerontology Research Center, Stockholm, Sweden
| | - Davide L Vetrano
- Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden
- Gerontology Research Center, Stockholm, Sweden
| |
Collapse
|
42
|
Xiong W, Feng S, Zhao Y, Liu X, Gong J. Revealing Landscape of Competing Endogenous RNA Networks in Sepsis-Induced Cardiovascular Diseases. Rev Cardiovasc Med 2023; 24:214. [PMID: 39077015 PMCID: PMC11266464 DOI: 10.31083/j.rcm2407214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 01/11/2023] [Accepted: 02/06/2023] [Indexed: 07/31/2024] Open
Abstract
Cardiovascular dysfunction induced by sepsis is one of the most common phenotypes of cardiovascular diseases (CVDs), which is closely related to the high mortality of sepsis and is an urgent health problem to be solved worldwide. Unfortunately, the exact pathogenesis and pathophysiology of sepsis-induced cardiovascular dysfunction are not clear. As a research hotspot in recent years, competing endogenous RNA (ceRNA) networks are involved in the modulation of the pathophysiological progression of many diseases, including sepsis-related CVDs. Both long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) can specifically bind to microRNAs (miRNAs) as ceRNAs to target messenger RNAs (mRNAs), forming a ceRNA network composed of lncRNA/circRNA-miRNA-mRNA. This review demonstrates the potential regulatory mechanism of the ceRNA networks in sepsis-induced cardiovascular toxicity, hoping to provide novel therapeutic strategies and monitoring targets for sepsis-related CVDs.
Collapse
Affiliation(s)
- Wei Xiong
- Laboratory of Clinical Research, Ziyang People’s Hospital, Ziyang Hospital of Sichuan Provincial People’s Hospital, 641300 Ziyang, Sichuan, China
- Department of Anesthesiology, West China Hospital, Sichuan University, 610041 Chengdu, Sichuan, China
| | - Shiyan Feng
- Laboratory of Clinical Research, Ziyang People’s Hospital, Ziyang Hospital of Sichuan Provincial People’s Hospital, 641300 Ziyang, Sichuan, China
- Emergency Medical Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology, 610072 Chengdu, Sichuan, China
| | - Yanhua Zhao
- Laboratory of Clinical Research, Ziyang People’s Hospital, Ziyang Hospital of Sichuan Provincial People’s Hospital, 641300 Ziyang, Sichuan, China
| | - Xinquan Liu
- Laboratory of Clinical Research, Ziyang People’s Hospital, Ziyang Hospital of Sichuan Provincial People’s Hospital, 641300 Ziyang, Sichuan, China
| | - Jian Gong
- Laboratory of Clinical Research, Ziyang People’s Hospital, Ziyang Hospital of Sichuan Provincial People’s Hospital, 641300 Ziyang, Sichuan, China
- Department of Emergency Critical Care, Ziyang People’s Hospital, Ziyang Hospital of Sichuan Provincial People’s Hospital, 641300 Ziyang, Sichuan, China
| |
Collapse
|
43
|
Regina J, Le Pogam MA, Niemi T, Akrour R, Pepe S, Lehn I, Wasserfallen JB, Calandra T, Meylan S. Sepsis awareness and knowledge amongst nurses, physicians and paramedics of a tertiary care center in Switzerland: A survey-based cross-sectional study. PLoS One 2023; 18:e0285151. [PMID: 37379303 DOI: 10.1371/journal.pone.0285151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Accepted: 04/06/2023] [Indexed: 06/30/2023] Open
Abstract
BACKGROUND Sepsis is a leading cause of morbidity and mortality. Prompt recognition and management are critical to improve outcomes. METHODS We conducted a survey among nurses and physicians of all adult departments of the Lausanne University Hospital (LUH) and paramedics transporting patients to our hospital. Measured outcomes included professionals' demographics (age, profession, seniority, unit of activity), quantification of prior sepsis education, self-evaluation, and knowledge of sepsis epidemiology, definition, recognition, and management. Correlation between surveyed personnel and sepsis perceptions and knowledge were assessed with univariable and multivariable logistic regression models. RESULTS Between January and October 2020, we contacted 1'216 of the 4'417 professionals (27.5%) of the LUH, of whom 1'116 (91.8%) completed the survey, including 619 of 2'463 (25.1%) nurses, 348 of 1'664 (20.9%) physicians and 149 of 290 (51.4%) paramedics. While 98.5% of the participants were familiar with the word "sepsis" (97.4% of nurses, 100% of physicians and 99.3% of paramedics), only 13% of them (physicians: 28.4%, nurses: 5.9%, paramedics: 6.8%) correctly identified the Sepsis-3 consensus definition. Similarly, only 48% and 49.3% of the physicians and 10.1% an 11.9% of the nurses knew that SOFA was a sepsis defining score and that the qSOFA score was a predictor of increased mortality, respectively. Furthermore, 15.8% of the physicians and 1.0% of the nurses knew the three components of the qSOFA score. For patients with suspected sepsis, 96.1%, 91.6% and 75.8% of physicians respectively chose blood cultures, broad-spectrum antibiotics and fluid resuscitation as therapeutic interventions to be initiated within 1 (76.4%) to 3 (18.2%) hours. For nurses and physicians, recent training correlated with knowledge of SOFA score (ORs [95%CI]: 3.956 [2.018-7.752] and 2.617 [1.527-4.485]) and qSOFA (ORs [95%CI]: 5.804 [2.653-9.742] and 2.291 [1.342-3.910]) scores purposes. Furthermore, recent training also correlated with adequate sepsis definition (ORs [95%CI]: 1.839 [1.026-3.295]) and the components of qSOFA (ORs [95%CI]: 2.388 [1.110-5.136]) in physicians. CONCLUSIONS This sepsis survey conducted among physicians, nurses and paramedics of a tertiary Swiss medical center identified a deficit of sepsis awareness and knowledge reflecting a lack of sepsis-specific continuing education requiring immediate corrective measures.
Collapse
Affiliation(s)
- Jean Regina
- Department of Medicine, Infectious Diseases Service, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
| | - Marie-Annick Le Pogam
- Centre for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland
| | - Tapio Niemi
- Centre for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland
| | - Rachid Akrour
- Service of Geriatrics and Geriatric Rehabilitation, Lausanne University Hospital, Lausanne, Switzerland
| | - Santino Pepe
- Medical Directorate, Lausanne University Hospital, Lausanne, Switzerland
| | - Isabelle Lehn
- Director of Nursing, Lausanne University Hospital, Lausanne, Switzerland
| | | | - Thierry Calandra
- Department of Medicine, Infectious Diseases Service, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
- Department of Medicine and Department of Laboratory Medicine and Pathology, Service of Immunology and Allergy, Center for Human Immunology Lausanne, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland
- Department of Infectious Diseases and Tropical Medicine, Necker-Enfants Malades University Hospital, University of Paris Cité, Paris, France
| | - Sylvain Meylan
- Department of Medicine, Infectious Diseases Service, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
| |
Collapse
|
44
|
Colbert JF, Kirsch JM, Erzen CL, Langouët-Astrié CJ, Thompson GE, McMurtry SA, Kofonow JM, Robertson CE, Kovacs EJ, Sullivan RC, Hippensteel JA, Sawant NV, De Nisco NJ, McCollister BD, Schwartz RS, Horswill AR, Frank DN, Duerkop BA, Schmidt EP. Aging-Associated Augmentation of Gut Microbiome Virulence Capability Drives Sepsis Severity. mBio 2023; 14:e0005223. [PMID: 37102874 PMCID: PMC10294665 DOI: 10.1128/mbio.00052-23] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Accepted: 04/04/2023] [Indexed: 04/28/2023] Open
Abstract
Prior research has focused on host factors as mediators of exaggerated sepsis-associated morbidity and mortality in older adults. This focus on the host, however, has failed to identify therapies that improve sepsis outcomes in the elderly. We hypothesized that the increased susceptibility of the aging population to sepsis is not only a function of the host but also reflects longevity-associated changes in the virulence of gut pathobionts. We utilized two complementary models of gut microbiota-induced experimental sepsis to establish the aged gut microbiome as a key pathophysiologic driver of heightened disease severity. Further murine and human investigations into these polymicrobial bacterial communities demonstrated that age was associated with only subtle shifts in ecological composition but also an overabundance of genomic virulence factors that have functional consequence on host immune evasion. IMPORTANCE Older adults suffer more frequent and worse outcomes from sepsis, a critical illness secondary to infection. The reasons underlying this unique susceptibility are incompletely understood. Prior work in this area has focused on how the immune response changes with age. The current study, however, focuses instead on alterations in the community of bacteria that humans live with within their gut (i.e., the gut microbiome). The central concept of this paper is that the bacteria in our gut evolve along with the host and "age," making them more efficient at causing sepsis.
Collapse
Affiliation(s)
- James F. Colbert
- Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA
- Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA
- Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado, USA
| | - Joshua M. Kirsch
- Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Christopher L. Erzen
- Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA
| | | | | | - Sarah A. McMurtry
- Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Jennifer M. Kofonow
- Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Charles E. Robertson
- Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Elizabeth J. Kovacs
- Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Ryan C. Sullivan
- Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Joseph A. Hippensteel
- Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Namrata V. Sawant
- Department of Biological Sciences, University of Texas at Dallas, Richardson, Texas, USA
| | - Nicole J. De Nisco
- Department of Biological Sciences, University of Texas at Dallas, Richardson, Texas, USA
- Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Bruce D. McCollister
- Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Robert S. Schwartz
- Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA
- Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado, USA
| | - Alexander R. Horswill
- Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA
- Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado, USA
| | - Daniel N. Frank
- Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Breck A. Duerkop
- Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Eric P. Schmidt
- Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA
- Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| |
Collapse
|
45
|
Vasconcelos I, Santos T. Nanotechnology Applications in Sepsis: Essential Knowledge for Clinicians. Pharmaceutics 2023; 15:1682. [PMID: 37376129 DOI: 10.3390/pharmaceutics15061682] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 05/29/2023] [Accepted: 06/06/2023] [Indexed: 06/29/2023] Open
Abstract
Sepsis is a life-threatening condition caused by a dysregulated host response to an invading pathogen such as multidrug-resistant bacteria. Despite recent advancements, sepsis is a leading cause of morbidity and mortality, resulting in a significant global impact and burden. This condition affects all age groups, with clinical outcomes mainly depending on a timely diagnosis and appropriate early therapeutic intervention. Because of the unique features of nanosized systems, there is a growing interest in developing and designing novel solutions. Nanoscale-engineered materials allow a targeted and controlled release of bioactive agents, resulting in improved efficacy with minimal side effects. Additionally, nanoparticle-based sensors provide a quicker and more reliable alternative to conventional diagnostic methods for identifying infection and organ dysfunction. Despite recent advancements, fundamental nanotechnology principles are often presented in technical formats that presuppose advanced chemistry, physics, and engineering knowledge. Consequently, clinicians may not grasp the underlying science, hindering interdisciplinary collaborations and successful translation from bench to bedside. In this review, we abridge some of the most recent and most promising nanotechnology-based solutions for sepsis diagnosis and management using an intelligible format to stimulate a seamless collaboration between engineers, scientists, and clinicians.
Collapse
Affiliation(s)
- Inês Vasconcelos
- School of Medicine, University of Minho, 4710-057 Braga, Portugal
- Department of Surgery and Physiology, Cardiovascular Research and Development Center-UnIC, Faculty of Medicine, University of Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
| | - Tiago Santos
- School of Medicine, University of Minho, 4710-057 Braga, Portugal
| |
Collapse
|
46
|
Choi H, Lee JY, Yoo H, Jeon K. Bioinformatics Analysis of Gene Expression Profiles for Diagnosing Sepsis and Risk Prediction in Patients with Sepsis. Int J Mol Sci 2023; 24:ijms24119362. [PMID: 37298316 DOI: 10.3390/ijms24119362] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 05/19/2023] [Accepted: 05/23/2023] [Indexed: 06/12/2023] Open
Abstract
: Although early recognition of sepsis is essential for timely treatment and can improve sepsis outcomes, no marker has demonstrated sufficient discriminatory power to diagnose sepsis. This study aimed to compare gene expression profiles between patients with sepsis and healthy volunteers to determine the accuracy of these profiles in diagnosing sepsis and to predict sepsis outcomes by combining bioinformatics data with molecular experiments and clinical information. We identified 422 differentially expressed genes (DEGs) between the sepsis and control groups, of which 93 immune-related DEGs were considered for further studies due to immune-related pathways being the most highly enriched. Key genes upregulated during sepsis, including S100A8, S100A9, and CR1, are responsible for cell cycle regulation and immune responses. Key downregulated genes, including CD79A, HLA-DQB2, PLD4, and CCR7, are responsible for immune responses. Furthermore, the key upregulated genes showed excellent to fair accuracy in diagnosing sepsis (area under the curve 0.747-0.931) and predicting in-hospital mortality (0.863-0.966) of patients with sepsis. In contrast, the key downregulated genes showed excellent accuracy in predicting mortality of patients with sepsis (0.918-0.961) but failed to effectively diagnosis sepsis.In conclusion, bioinformatics analysis identified key genes that may serve as biomarkers for diagnosing sepsis and predicting outcomes among patients with sepsis.
Collapse
Affiliation(s)
- Hayoung Choi
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul 07441, Republic of Korea
| | - Jin Young Lee
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
| | - Hongseok Yoo
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
| | - Kyeongman Jeon
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
- Department of Health Sciences and Technology, SAIHST, Sungkyunkawan University, Seoul 06351, Republic of Korea
| |
Collapse
|
47
|
Li X, Zhai Y, Yao Q, The E, Ao L, Fullerton DA, Yu KJ, Meng X. Up-regulation of Myocardial Klotho Expression to Promote Cardiac Functional Recovery in Old Mice following Endotoxemia. RESEARCH SQUARE 2023:rs.3.rs-2949854. [PMID: 37292905 PMCID: PMC10246261 DOI: 10.21203/rs.3.rs-2949854/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Objective Endotoxemic cardiac dysfunction contributes to greater morbidity and mortality in elderly patients with sepsis. This study tested the hypothesis that Klotho insufficiency in aging heart exaggerates and prolongs myocardial inflammation to hinder cardiac function recovery following endotoxemia. Methods Endotoxin (0.5 mg/kg, iv) was administered to young adult (3-4 months) and old (18-22 months) mice with or without subsequent treatment with recombinant interleukin-37 (IL-37, 50 μg/kg, iv) or recombinant Klotho (10 μg/kg, iv). Cardiac function was analyzed using a microcatheter 24, 48 and 96 h later. Myocardial levels of Klotho, ICAM-1, VCAM-1 and IL-6 were determined by immunoblotting and ELISA. Results In comparison to young adult mice, old mice had worse cardiac dysfunction accompanied by greater myocardial levels of ICAM-1, VCAM-1 and IL-6 at each time point following endotoxemia and failed to fully recover cardiac function by 96 h. The exacerbated myocardial inflammation and cardiac dysfunction were associated with endotoxemia-caused further reduction of lower myocardial Klotho level in old mice. Recombinant IL-37 promoted inflammation resolution and cardiac functional recovery in old mice. Interestingly, recombinant IL-37 markedly up-regulated myocardial Klotho levels in old mice with or without endotoxemia. Similarly, recombinant Klotho suppressed myocardial inflammatory response and promoted inflammation resolution in old endotoxemic mice, leading to complete recovery of cardiac function by 96 h. Conclusion Myocardial Klotho insufficiency in old endotoxemic mice exacerbates myocardial inflammatory response, impairs inflammation resolution and thereby hinders cardiac functional recovery. IL-37 is capable of up-regulating myocardial Klotho expression to improve cardiac functional recovery in old endotoxemic mice.
Collapse
|
48
|
Keegan A, Strahley A, Taylor SP, Wilson TM, Shah MD, Williamson J, Palakshappa JA. Older Adults' Perspectives on Screening for Cognitive Impairment Following Critical Illness: Pre-Implementation Qualitative Study. Crit Care Explor 2023; 5:e0920. [PMID: 37197588 PMCID: PMC10184981 DOI: 10.1097/cce.0000000000000920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/19/2023] Open
Abstract
Screening for cognitive impairment following ICU discharge is recommended but not part of routine care. We sought to understand older adults' perspectives on screening for cognitive impairment following an ICU admission to inform the design and delivery of a cognitive screening intervention. DESIGN Qualitative study using semi-structured interviews. SUBJECTS Adults 60 years and older within 3 months of discharge from an ICU in an academic health system. INTERVENTIONS Interviews were conducted via telephone, audio recorded and transcribed verbatim. All transcripts were coded in duplicate. Discrepancies were resolved by consensus. Codes were organized into themes and subthemes inductively. MEASUREMENTS AND MAIN RESULTS We completed 22 interviews. The mean age of participants was 71 ± 6 years, 14 (63.6%) were men, 16 (72.7%) were White, and 6 (27.3%) were Black. Thematic analysis was organized around four themes: 1) receptivity to screening, 2) communication preferences, 3) information needs, and 4) provider involvement. Most participants were receptive to cognitive screening; this was influenced by trust in their providers and prior experience with cognitive screening and impairment. Participants preferred simple, direct, compassionate communication. They wanted to understand the screening procedure, the rationale for screening, and expectations for recovery. Participants desired input from their primary care provider to have their cognitive screening results placed in the context of their overall health, because they had a trusted relationship, and for convenience. CONCLUSIONS Participants demonstrated limited understanding of and exposure to cognitive screening but see it as potentially beneficial following an ICU stay. Providers should use simple, straightforward language and place emphasis on expectations. Resources may be needed to assist primary care providers with capacity to provide cognitive screening and interpret results for ICU survivors. Implementation strategies can include educational materials for clinicians and patients on rationale for screening and recovery expectations.
Collapse
Affiliation(s)
- Alek Keegan
- Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC
| | - Ashley Strahley
- Department of Social Sciences and Health Policy, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC
| | - Stephanie P Taylor
- Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC
- Carolinas Medical Center, Atrium Health, Charlotte, NC
| | - Taniya M Wilson
- Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC
| | - Meehir D Shah
- Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC
| | - Jeff Williamson
- Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC
| | - Jessica A Palakshappa
- Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC
| |
Collapse
|
49
|
Abstract
PURPOSE OF REVIEW Sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, is a leading cause of hospital and ICU admission. The central and peripheral nervous system may be the first organ system to show signs of dysfunction, leading to clinical manifestations such as sepsis-associated encephalopathy (SAE) with delirium or coma and ICU-acquired weakness (ICUAW). In the current review, we want to highlight developing insights into the epidemiology, diagnosis, prognosis, and treatment of patients with SAE and ICUAW. RECENT FINDINGS The diagnosis of neurological complications of sepsis remains clinical, although the use of electroencephalography and electromyography can support the diagnosis, especially in noncollaborative patients, and can help in defining disease severity. Moreover, recent studies suggest new insights into the long-term effects associated with SAE and ICUAW, highlighting the need for effective prevention and treatment. SUMMARY In this manuscript, we provide an overview of recent insights and developments in the prevention, diagnosis, and treatment of patients with SAE and ICUAW.
Collapse
Affiliation(s)
- Simone Piva
- Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia
- Department of Anesthesia, Critical Care and Emergency, Spedali Civili University Hospital
| | - Michele Bertoni
- Department of Anesthesia, Critical Care and Emergency, Spedali Civili University Hospital
| | - Nicola Gitti
- Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia
| | - Francesco A. Rasulo
- Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia
- Department of Anesthesia, Critical Care and Emergency, Spedali Civili University Hospital
- ’Alessandra Bono’ University Research Center on Long-term Outcome in Critical Illness Survivors, University of Brescia, Brescia, Italy
| | - Nicola Latronico
- Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia
- Department of Anesthesia, Critical Care and Emergency, Spedali Civili University Hospital
- ’Alessandra Bono’ University Research Center on Long-term Outcome in Critical Illness Survivors, University of Brescia, Brescia, Italy
| |
Collapse
|
50
|
Medeiros SK, Sharma N, Dwivedi D, Cani E, Zhou J, Dwivedi N, Sohrabipour S, Liaw PC. THE EFFECTS OF DNASE I AND LOW-MOLECULAR-WEIGHT HEPARIN IN A MURINE MODEL OF POLYMICROBIAL ABDOMINAL SEPSIS. Shock 2023; 59:666-672. [PMID: 36852972 DOI: 10.1097/shk.0000000000002095] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2023]
Abstract
ABSTRACT Introduction: Cell-free DNA (CFDNA) has emerged as a prognostic biomarker in patients with sepsis. Circulating CFDNA is hypothesized to be associated with histones in the form of nucleosomes. In vitro, DNA activates coagulation and inhibits fibrinolysis, whereas histones activate platelets and are cytotoxic to endothelial cells. Previous studies have targeted CFDNA or histones in animal models of sepsis using DNase I or heparins, respectively, which has reduced inflammatory and thrombosis markers, thereby improving survival. In this study, we explored the possibility that the combination of DNase I and a low-molecular weight heparin (LMWH) may be a better therapeutic approach than monotherapy in a murine model of abdominal sepsis. Methods: C57Bl/6 mice (8-12 weeks old, both sexes) were subjected to either cecal ligation and puncture or sham surgery. Mice were given antibiotics, fluids, and either saline, DNase I (intraperitoneally, 20 mg/kg/8 h), LMWH (dalteparin, subcutaneously 500 IU/kg/12 h), or a combination of both (n = 12-31). Mice were monitored over 72 h for survival. Organs and blood were harvested for analysis. Levels of LMWH, CFDNA, IL-6, citrullinated histone-H3, thrombin-antithrombin complexes, and protein C were measured in plasma. Results: Administration of either DNase I (81.8%) or LMWH (83.3%, prophylactic range of 0.12 ± 0.07 IU/mL achieved) improved the survival of septic mice compared with saline- (38.7%) and combination-treated mice (48.8%, P < 0.05). Combination-treated mice also showed a small but insignificant improvement in survival compared with saline-treated cecal ligation and puncture mice. Monotherapies may be improving survival by reducing blood bacterial loads, citrullinated histone-H3, and thrombin-antithrombin complexes, and improving protein C levels. Conclusions: Compared with saline- and combination-treated mice, administration of monotherapies to septic mice improved survival. These findings suggest that there may be a negative drug-drug interaction between DNase I and LMWH when DNase I is administered intraperitoneally in a murine model of polymicrobial abdominal sepsis.
Collapse
Affiliation(s)
| | | | | | | | | | - Naviya Dwivedi
- Thrombosis and Atherosclerosis Research Institute, Hamilton, Canada
| | | | | |
Collapse
|