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Desman JM, Hong ZW, Sabounchi M, Sawant AS, Gill J, Costa AC, Kumar G, Sharma R, Gupta A, McCarthy P, Nandwani V, Powell D, Carideo A, Goodwin D, Ahmed S, Gidwani U, Levin MA, Varghese R, Filsoufi F, Freeman R, Shetreat-Klein A, Charney AW, Hofer I, Chan L, Reich D, Kovatch P, Kohli-Seth R, Kraft M, Agrawal P, Kellum JA, Nadkarni GN, Sakhuja A. A distributional reinforcement learning model for optimal glucose control after cardiac surgery. NPJ Digit Med 2025; 8:313. [PMID: 40425725 PMCID: PMC12116759 DOI: 10.1038/s41746-025-01709-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Accepted: 05/08/2025] [Indexed: 05/29/2025] Open
Abstract
This study introduces Glucose Level Understanding and Control Optimized for Safety and Efficacy (GLUCOSE), a distributional offline reinforcement learning algorithm for optimizing insulin dosing after cardiac surgery. Trained on 5228 patients, tested on 920, and externally validated on 649, GLUCOSE achieved a mean estimated reward of 0.0 [-0.07, 0.06] in internal testing and -0.63 [-0.74, -0.52] in external validation, outperforming clinician returns of -1.29 [-1.37, -1.20] and -1.02 [-1.16, -0.89]. In multi-phase human validation, GLUCOSE first showed a significantly lower mean absolute error (MAE) in insulin dosing, with 0.9 units MAE versus clinicians' 1.97 units (p < 0.001) in internal testing and 1.90 versus 2.24 units (p = 0.003) in external validation. The second and third phases found GLUCOSE's performance as comparable to or exceeding that of senior clinicians in MAE, safety, effectiveness, and acceptability. These findings suggest GLUCOSE as a robust tool for improving postoperative glucose management.
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Affiliation(s)
- Jacob M Desman
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Division of Data-Driven and Digital Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Zhang-Wei Hong
- Improbable AI Lab, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Moein Sabounchi
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Division of Data-Driven and Digital Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ashwin S Sawant
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Division of Data-Driven and Digital Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Division of Hospital Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jaskirat Gill
- Institute for Critical Care Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ana C Costa
- Department of Cardiothoracic Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Gagan Kumar
- Department of Pulmonary and Critical Care Medicine, Northeast Georgia Medical Center, Gainesville, GA, USA
| | - Rajeev Sharma
- Division of Endocrinology, Hackensack University Medical Center, Hackensack, NJ, USA
| | - Arpeta Gupta
- Division of Endocrinology, Millenium Physician Group, Jacksonville, FL, USA
| | - Paul McCarthy
- Section of Cardiovascular Critical Care, Department of Cardiovascular and Thoracic Surgery, West Virginia University, Morgantown, WV, USA
| | - Veena Nandwani
- Section of Cardiovascular Critical Care, Department of Cardiovascular and Thoracic Surgery, West Virginia University, Morgantown, WV, USA
| | - Doug Powell
- Section of Cardiovascular Critical Care, Department of Cardiovascular and Thoracic Surgery, West Virginia University, Morgantown, WV, USA
| | - Alexandra Carideo
- Institute for Critical Care Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Donnie Goodwin
- Section of Cardiovascular Critical Care, Department of Cardiovascular and Thoracic Surgery, West Virginia University, Morgantown, WV, USA
| | - Sanam Ahmed
- Institute for Critical Care Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Umesh Gidwani
- Institute for Critical Care Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Matthew A Levin
- Department of Anesthesiology, Perioperative, and Pain Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Robin Varghese
- Institute for Critical Care Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Cardiothoracic Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Farzan Filsoufi
- Department of Cardiothoracic Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Robert Freeman
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Avniel Shetreat-Klein
- Department of Rehabilitation and Physical Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Alexander W Charney
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ira Hofer
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Division of Data-Driven and Digital Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Anesthesiology, Perioperative, and Pain Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Lili Chan
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Division of Data-Driven and Digital Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - David Reich
- Department of Anesthesiology, Perioperative, and Pain Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Patricia Kovatch
- Scientific Computing, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Roopa Kohli-Seth
- Institute for Critical Care Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Monica Kraft
- Samuel Bronfman Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Pulkit Agrawal
- Improbable AI Lab, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - John A Kellum
- Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Girish N Nadkarni
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Division of Data-Driven and Digital Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ankit Sakhuja
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Division of Data-Driven and Digital Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Institute for Critical Care Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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Ren D, Dang X, Ni T, Zhou J, Zhang Z, Fu S, Zhang W, Yan T, Zhao Y, Liu J. On-treatment serum albumin levels can predict 28-day mortality and guide albumin infusion in sepsis patients. Front Med (Lausanne) 2025; 12:1490838. [PMID: 40438354 PMCID: PMC12116570 DOI: 10.3389/fmed.2025.1490838] [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: 09/03/2024] [Accepted: 04/07/2025] [Indexed: 06/01/2025] Open
Abstract
Background As the most abundant protein in plasma, albumin (ALB) presents close association with prognosis of septic patients. Whereas, the benefit and the target level of ALB infusion remain controversial. Methods We conducted a retrospective investigation to assess whether on-treatment ALB levels could predict 28-day mortality and try to identify the optimal level for ALB infusion. All patients diagnosed as sepsis from January 2016 to December 2020 were recruited and re-evaluated using Sepsis-3 criteria. Results A total of 199 eligible patients were enrolled in this study. Compared with the survival group, the non-survival group had more males (73.97 vs. 56.35%), older patients (62.78 ± 15.93 vs. 56.43 ± 18.46), and a higher proportion of Gram-positive bacterial infection (27.40 vs. 23.02%), higher Sequential Organ Failure Assessment (SOFA) score (7.00-13.00 vs. 6.00-12.00), higher APACHE II score (18.25-29.00 vs. 15.00-26.00), higher PCT (2.84-49.18 vs. 2.43-19.14), more patients with septic shock (65.75%vs. 43.65%), shorter ICU-stay days (11.04 ± 6.28 vs. 14.83 ± 8.58), longer mechanical ventilation days (7.23 ± 7.07 vs. 5.04 ± 8.52), with statistically significant differences (p < 0.050). Furthermore, we identified that the ALB level on day 7 (HR, 0.920; 95% CI, 0.847 to 0.999; p = 0.046) and the maximum ALB level within the first 14 days (HR, 0.900; 95% CI, 0.838 to 0.967; p = 0.004) were independent protective factor for the 28-day prognosis in septic patients. Moreover, ROC curve analysis indicated that optimal target level for first 14-day maximum and on day 7 were 33.45 g/L and 27.85 g/L, respectively. Correspondingly, a negative correlation between ALB level and mortality was defined with Kaplan-Meier survival curve analysis. Further subgroup analysis showed that the group with ALB above the cut-off value was associated with favorable outcomes in female patients under 60 years, with SOFA score less than 7, and APACHE II score less than 19. Conclusion ALB levels on day 7 and the maximum ALB level within first 14 days after ICU admission were closely associated with 28-day mortality. 27.85 g/L would work as the target level of ALB infusion on 7 day to improve the prognosis of sepsis patients.
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Affiliation(s)
- Danfeng Ren
- Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Clinical Medical Research Center for Infectious Diseases, Xi’an, China
| | - Xiangyun Dang
- Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Clinical Medical Research Center for Infectious Diseases, Xi’an, China
| | - Tianzhi Ni
- Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Clinical Medical Research Center for Infectious Diseases, Xi’an, China
| | - Jingwen Zhou
- Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Clinical Medical Research Center for Infectious Diseases, Xi’an, China
| | - Ze Zhang
- Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Clinical Medical Research Center for Infectious Diseases, Xi’an, China
| | - Shan Fu
- Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Clinical Medical Research Center for Infectious Diseases, Xi’an, China
| | - Wentao Zhang
- Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Clinical Medical Research Center for Infectious Diseases, Xi’an, China
| | - Taotao Yan
- Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Clinical Medical Research Center for Infectious Diseases, Xi’an, China
| | - Yingren Zhao
- Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Clinical Medical Research Center for Infectious Diseases, Xi’an, China
| | - Jinfeng Liu
- Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Clinical Medical Research Center for Infectious Diseases, Xi’an, China
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Zhang T, Pan Y, Sawa T, Akaike T, Matsunaga T. Supersulfide donors and their therapeutic targets in inflammatory diseases. Front Immunol 2025; 16:1581385. [PMID: 40308575 PMCID: PMC12040673 DOI: 10.3389/fimmu.2025.1581385] [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: 02/22/2025] [Accepted: 03/31/2025] [Indexed: 05/02/2025] Open
Abstract
Inflammation is one defense mechanism of the body that has multiple origins, ranging from physical agents to infectious agents including viruses and bacteria. The resolution of inflammation has emerged as a critical endogenous process that protects host tissues from prolonged or excessive inflammation, which can become chronic. Failure of the inflammation resolution is a key pathological mechanism that drives the progression of numerous inflammatory diseases. Owing to the various side effects of currently available drugs to control inflammation, novel therapeutic agents that can prevent or suppress inflammation are needed. Supersulfides are highly reactive and biologically potent molecules that function as antioxidants, redox regulators, and modulators of cell signaling. The catenation state of individual sulfur atoms endows supersulfides with unique biological activities. Great strides have recently been made in achieving a molecular understanding of these sulfur species, which participate in various physiological and pathological pathways. This review mainly focuses on the anti-inflammatory effects of supersulfides. The review starts with an overview of supersulfide biology and highlights the roles of supersulfides in both immune and inflammatory responses. The various donors used to generate supersulfides are assessed as research tools and potential therapeutic agents. Deeper understanding of the molecular and cellular bases of supersulfide-driven biology can help guide the development of innovative therapeutic strategies to prevent and treat diseases associated with various immune and inflammatory responses.
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Affiliation(s)
- Tianli Zhang
- Center for Integrated Control, Epidemiology and Molecular Pathophysiology of Infectious Diseases, Akita University, Akita, Japan
| | - Yuexuan Pan
- Department of Redox Molecular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tomohiro Sawa
- Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Takaaki Akaike
- Department of Redox Molecular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
- Shimadzu × Tohoku University Supersulfides Life Science Co-creation Research Center, Sendai, Japan
| | - Tetsuro Matsunaga
- Center for Integrated Control, Epidemiology and Molecular Pathophysiology of Infectious Diseases, Akita University, Akita, Japan
- Shimadzu × Tohoku University Supersulfides Life Science Co-creation Research Center, Sendai, Japan
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Ford JS, Morrison JC, Kyaw M, Hewlett M, Tahir P, Jain S, Nemati S, Malhotra A, Wardi G. The Effect of Severe Sepsis and Septic Shock Management Bundle (SEP-1) Compliance and Implementation on Mortality Among Patients With Sepsis : A Systematic Review. Ann Intern Med 2025; 178:543-557. [PMID: 39961104 PMCID: PMC12015987 DOI: 10.7326/annals-24-02426] [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] [Indexed: 03/06/2025] Open
Abstract
BACKGROUND The Centers for Medicare & Medicaid Services (CMS) Severe Sepsis and Septic Shock Management Bundle (SEP-1) is now included in the Hospital Value-Based Purchasing (VBP) Program. PURPOSE To assess the evidence supporting SEP-1 compliance or SEP-1 implementation in improving sepsis mortality. DATA SOURCES PubMed, Web of Science, EMBASE, CINAHL Complete, and Cochrane Library from inception to 26 November 2024. STUDY SELECTION Studies of adults with sepsis that included 3- or 6-hour sepsis bundles defined by SEP-1 specifications. DATA EXTRACTION Article screening, full-text review, data extraction, and risk-of-bias assessment were independently performed by 2 authors. Level of evidence was determined using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria and National Quality Forum criteria. DATA SYNTHESIS A total of 4403 unique references were screened, and 17 studies were included. Twelve studies assessed the relationship between SEP-1 compliance and mortality; 5 showed statistically significant benefit, whereas 7 did not. Among studies showing benefit, 1 did not adjust for confounders, 1 found benefit only among patients with severe sepsis, 1 included only patients with septic shock, and 1 included only Medicare beneficiaries. Five studies assessed the relationship between SEP-1 implementation and sepsis mortality; only 1 showed significant benefit, but it did not adjust for mortality trends before SEP-1 implementation. All 17 studies were observational, and none had low risk of bias. LIMITATIONS The conclusions are limited by the underlying quality of the available studies, as all were observational. Because there was considerable methodologic heterogeneity among the included studies, a meta-analysis was not performed as the results could have been misleading. CONCLUSION This review found no moderate- or high-level evidence to support that compliance with or implementation of SEP-1 was associated with sepsis mortality. CMS should reconsider the addition of SEP-1 to the Hospital VBP Program. PRIMARY FUNDING SOURCE None. (PROSPERO: CRD42023482787).
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Affiliation(s)
- James S Ford
- Department of Emergency Medicine, University of California San Diego, San Diego, California (J.S.F.)
| | - Joseph C Morrison
- School of Medicine, University of California, Davis, Sacramento, California (J.C.M.)
| | - May Kyaw
- Department of Medicine, University of California San Diego, San Diego, California (M.K., A.M.)
| | - Meghan Hewlett
- Department of Emergency Medicine, University of California, San Francisco, San Francisco, California (M.H.)
| | - Peggy Tahir
- UCSF Library, University of California, San Francisco, San Francisco, California (P.T.)
| | - Sonia Jain
- Biostatistics Research Center, Herbert Wertheim School of Public Health, University of California San Diego, San Diego, California (S.J.)
| | - Shamim Nemati
- Department of Emergency Medicine and Department of Medicine, University of California San Diego, San Diego, California (S.N., G.W.)
| | - Atul Malhotra
- Department of Medicine, University of California San Diego, San Diego, California (M.K., A.M.)
| | - Gabriel Wardi
- Department of Emergency Medicine and Department of Medicine, University of California San Diego, San Diego, California (S.N., G.W.)
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Parjiea CP, Sievert M, Haj Khalaf MA, Ihmsen H, Higaze M, Gehrking M, Wehrfritz A, Sirbu H. Management and Outcomes of Descending Necrotizing Mediastinitis: A 15-Year Experience. J Clin Med 2025; 14:1593. [PMID: 40095594 PMCID: PMC11899804 DOI: 10.3390/jcm14051593] [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: 02/04/2025] [Revised: 02/24/2025] [Accepted: 02/25/2025] [Indexed: 03/19/2025] Open
Abstract
Background/Objectives: Descending necrotising mediastinitis (DNM) is a severe, life-threatening infection that originates from the oropharyngeal or odontogenic regions and spreads to the mediastinum. It poses significant challenges due to its rapid progression and high morbidity. Methods: This monocentric, retrospective study analysed the records of 22 patients treated for DNM between 2008 and 2022. Diagnosis relied on characteristic clinical, radiological, and intraoperative findings linking oropharyngeal or cervical infections to mediastinitis. Contrast-enhanced computed tomography (CT) was used in all cases for diagnosis. Data collected included demographics, comorbidities, surgical interventions, time from diagnosis to surgery, re-operations, and complications. Microbiological analyses targeted aerobic and anaerobic pathogens. Results: The study included 22 patients (mean age 60 ± 9 years, 59% male) with DNM. The primary sources of infection were oropharyngeal (77%) and odontogenic (23%). Hypertension (86%), diabetes (68%), and cardiac arrhythmias (59%) were common comorbidities. Thoracotomy with mediastinal drainage and debridement was performed in 95% of patients, while 45% underwent cervicotomy and 82% required tracheostomy. The median intensive care unit (ICU) and hospital stays were 21 and 30 days, respectively. Delayed surgery (>24 h) significantly prolonged hospital stays (median: 62 vs. 28 days, p = 0.05). Re-operations were required in 82% of patients, with longer ICU stays observed in this group (median: 25 vs. 7 days, p = 0.003). Sepsis occurred in 55% and was associated with a higher tracheostomy rate (100% vs. 60%, p = 0.029). The mortality rate was 9%. Conclusions: Early recognition and prompt aggressive surgical intervention are paramount in managing DNM to mitigate complications and improve survival.
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Affiliation(s)
- Chirag P. Parjiea
- Department of Thoracic Surgery, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
| | - Matti Sievert
- Department of Otorhinolaryngology-Head and Neck Surgery, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
| | - Mohamed Anwar Haj Khalaf
- Department of Thoracic Surgery, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
| | - Harald Ihmsen
- Department of Anaesthesiology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
| | - Mostafa Higaze
- Department of Thoracic Surgery, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
| | - Mika Gehrking
- Department of Otorhinolaryngology-Head and Neck Surgery, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
| | - Andreas Wehrfritz
- Department of Anaesthesiology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
| | - Horia Sirbu
- Department of Thoracic Surgery, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
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Oh EJ, Cho EA, Jun J, Lee SH, Lee S, Ahn JH. Dynamic Arterial Elastance as a Predictor of Intraoperative Fluid Responsiveness in Elderly Patient over 70 Years of Age Undergoing Spine Surgery in the Prone Position Under General Anesthesia: A Validation Study. J Clin Med 2025; 14:1247. [PMID: 40004778 PMCID: PMC11856236 DOI: 10.3390/jcm14041247] [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: 12/27/2024] [Revised: 02/03/2025] [Accepted: 02/06/2025] [Indexed: 02/27/2025] Open
Abstract
Background: Optimizing fluid therapy is critical for maintaining hemodynamic stability in elderly patients undergoing major surgeries. Dynamic arterial elastance (Eadyn), defined as the ratio of pulse pressure variation (PPV) to stroke volume variation (SVV), has been proposed as a predictor of fluid responsiveness, especially in challenging conditions like prone-positioned spine surgery under general anesthesia. Methods: Hemodynamic parameters were measured before and after fluid loading with 500 mL of crystalloid solution. Patients were classified as responders or non-responders based on a ≥15% increase in mean arterial pressure (MAP) post-fluid administration. Predictive performance of these parameters was assessed using receiver operating characteristic (ROC) analysis. Results: Of the 37 patients, 15 were classified as responders and 22 as non-responders. Eadyn demonstrated poor predictive performance (AUC = 0.508). In contrast, SVV (AUC = 0.808), PPV (AUC = 0.738), and C (AUC = 0.741) exhibited moderate to high predictive ability. Responders exhibited significantly higher baseline SVV, PPV, and net arterial compliance compared to non-responders. Conclusions: Dynamic arterial elastance (Eadyn) showed limited predictive ability for fluid responsiveness in elderly patients undergoing spine surgery in the prone position. In contrast, stroke volume variation (SVV), pulse pressure variation (PPV), and net arterial compliance (C) demonstrated superior reliability, with SVV emerging as the most accurate predictor.
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Affiliation(s)
| | | | | | | | | | - Jin Hee Ahn
- Department of Anesthesiology and Pain Medicine, Kangbuk Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 03063, Republic of Korea; (E.J.O.); (E.A.C.); (J.J.); (S.H.L.); (S.L.)
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Yang R, Hu C, Zhuo Y, Tan Q, Shen Y, Jiang K, Xia Q, Deng L. Comparative efficacy of Chinese tonic medicines for treating sepsis or septic shock: A systematic review and Bayesian network meta-analysis of randomized controlled trials. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2025; 136:156295. [PMID: 39642462 DOI: 10.1016/j.phymed.2024.156295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 11/09/2024] [Accepted: 11/24/2024] [Indexed: 12/09/2024]
Abstract
BACKGROUND Sepsis or septic shock is a life-threatening medical emergency with a poor prognosis and a high economic burden for both individuals and healthcare resources. Evidence suggests that Chinese tonic medicines (CTMs), as adjuvant treatments, are effective in treating this disease. Nevertheless, the ongoing discourse regarding the optimal CTMs persists. This study was conducted to further explore the comparative effectiveness of CTMs for patients with sepsis or septic shock. METHODS We systematically searched Pubmed, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature (CBM), Chinese National Knowledge Infrastructure (CNKI), Wanfang database, VIP database from inception to November 15, 2023. Primary outcomes encompassed the delta Sequential Organ Failure Assessment (ΔSOFA) score at day 7 after interventions and 28-day mortality. Secondary outcomes included delta serum lactate (ΔLac) and delta mean arterial pressure (ΔMAP) levels at day 7 after interventions, as well as the duration of vasoactive drug administration. The safety outcome was adverse drug reactions or adverse drug events (ADRs/ADEs). The risk ratio (RR) and mean difference (MD) with a 95 % confidence interval (95 %CI) were selected as effect measures. The Bayesian network meta-analysis was conducted by R version 4.2.2 software. The surface under the cumulative ranking curve (SUCRA) values were used to rank each treatment. The Cochrane Risk of Bias V.2.0 tool was employed to assess the within-study risk of bias. The CINeMA (Confidence in Network Meta-Analysis) web application was utilized to assess the quality of evidence. This protocol was prospectively registered in PROSPERO (CRD4202348572). RESULTS A total of 45 randomized controlled trials (RCTs) involving 3433 patients were identified in this study. Seven CTMs including Shenfu injection (SF), Shenmai injection (SM), Sini decoction (SN), Shenfu and Shengmai granules (SF+SGM), Shengmai injection (SGM), Yiqifumai injection (YQFM), and Shenqifuzheng injection (SQFZ) were involved. Regarding the ΔSOFA score, interventions combining SM with Western medicine (WM) (MD, -2.77; 95 %CI, -3.28 to -2.27), YQFM+WM (MD, -1.76; 95 %CI, -2.73 to -0.79), SGM+WM (MD, -1.11; 95 %CI, -1.88 to -0.34), and SF+WM (MD, -0.98; 95 %CI, -1.17 to -0.78) demonstrated superiority over WM alone. According to the SUCRA values, SM+WM (99.28 %) achieved the highest ranking for the ΔSOFA score. Concerning 28-day mortality, SM+WM (RR, 0.51; 95 %CI, 0.35 to 0.72) and SF+WM (RR, 0.73; 95 %CI, 0.65 to 0.83) exhibited a superior effect in reducing 28-day mortality. Based on the SUCRA values, SM+WM (82.49 %) secured the top ranking for 28-day mortality. Among the secondary outcomes, SM+WM (MD, -2.50; 95 %CI, -4.15 to -0.83; SUCRA, 94.27 %) emerged as the most favorable in reducing serum lactate levels. SF+WM (MD, 10.78; 95 %CI, 3.11 to 18.71; SCURA, 78.3 %) exhibited superior effectiveness compared to other treatments in improving mean arterial pressure (MAP). The certainty of evidence for these outcomes was assessed as low. CONCLUSION CTMs combined with WM led to a significant improvement in ΔSOFA score and MAP, as well as a reduction in 28-day mortality and serum lactate levels. SM+WM emerged as the optimal treatment regimen for enhancing ΔSOFA, reducing 28-day mortality, and lowering serum lactate levels. Additionally, SF+WM exhibited superiority in improving MAP. Nevertheless, there is a need for large-scale, multicenter, and direct comparative RCTs to generate higher-quality evidence.
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Affiliation(s)
- Rui Yang
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Cheng Hu
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yuxin Zhuo
- West China Medical College, Sichuan University, Chengdu 610041, China
| | - Qingyuan Tan
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yuxin Shen
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Kun Jiang
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Qing Xia
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
| | - Lihui Deng
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
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Rapszky GA, Do To UN, Kiss VE, Kói T, Walter A, Gergő D, Meznerics FA, Rakovics M, Váncsa S, Kemény LV, Csupor D, Hegyi P, Filbin MR, Varga C, Fenyves BG. Rapid molecular assays versus blood culture for bloodstream infections: a systematic review and meta-analysis. EClinicalMedicine 2025; 79:103028. [PMID: 39968206 PMCID: PMC11833021 DOI: 10.1016/j.eclinm.2024.103028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 12/07/2024] [Accepted: 12/12/2024] [Indexed: 02/20/2025] Open
Abstract
Background Timely management of sepsis with early targeted antimicrobial therapy improves patient outcomes. Rapid molecular assays (RMAs) have emerged, enabling the detection of bloodstream infection (BSI) with a shorter turnaround time than blood cultures (BCs). The accuracy of several RMAs has not been comprehensively reviewed. We aimed to identify commercial RMAs reported in the literature and evaluate their diagnostic performance compared to BC. Methods A systematic review and meta-analysis was conducted, covering MEDLINE, Cochrane Library, Embase, and Web of Science from inception to September 23, 2024. Eligible studies included patients with suspected or documented BSI, tested with both an RMA (turnaround time of ≤12 h, targeting ≥20 pathogens) and BC. Non-original research articles and animal studies were excluded. The primary outcomes were pooled sensitivity and specificity of RMAs for pathogen detection compared to BC. Bivariate analysis was used to produce summary receiver operating characteristic plots and diagnostic metric measures stratified by different units of analysis (sample versus patient), RMA types, and patient populations. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) and Quality Assessment of Diagnostic Accuracy Studies-Comparative (QUADAS-C) tools. The study was registered with PROSPERO, CRD42022377280. Findings A total of 63,916 articles were identified, of which 104 were included in the qualitative synthesis and 75 in the quantitative synthesis, covering 17,952 samples and 11,393 patients analyzed separately. Eleven RMAs were identified, with four included in the RMA-based subgroup analysis (LightCycler SeptiFast Test MGRADE®, IRIDICA BAC BSI assay, SepsiTest, MagicPlex Sepsis Test) and five additional ones in the pooled analysis (UMD-SelectNA, VYOO®, MicrobScan assay, MicrobScan-Kairos24/7, REBA Sepsis-ID test). Two RMAs were included in the qualitative synthesis only (InfectID-BSI, Pilot Gene Technology droplet digital polymerase chain reaction). Pooled specificity of RMAs was higher (0.858, 95% confidence interval (CI) 0.830-0.883) than sensitivity (0.659, 95% CI 0.594-0.719) by patient. Sensitivities varied by RMA type from 0.492 (95% CI 0.390-0.594, MagicPlex Sepsis Test) to 0.783 (95% CI 0.662-0.870, IRIDICA BAC BSI assay) by patient. Specificities varied more by patient population, ranging from 0.811 (95% CI 0.716-0.879) in the intensive care population to 0.892 (95% CI 0.838-0.930) in the emergency department population, by patient. Similar metrics were observed when the analysis was done by sample. Risk of bias was judged to be high in all included articles. Interpretation Despite their shorter turnaround time, low sensitivity means RMAs cannot replace BCs. However, our data indicate that RMAs may have value as an add-on test by increasing pathogen detection rates. Higher-sensitivity RMAs are needed which could possibly be achieved by expanding pathogen coverage and increasing blood sample volumes. High-quality implementation studies and standardized reporting are required to assess the clinical advantages of RMAs. Funding Centre for Translational Medicine, Semmelweis University.
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Affiliation(s)
- Gabriella Anna Rapszky
- Department of Emergency Medicine, Semmelweis University, Budapest, Hungary
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Uyen Nguyen Do To
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- András Pető Faculty, Semmelweis University, Budapest, Hungary
| | | | - Tamás Kói
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Budapest University of Technology and Economics, Department of Stochastics, Budapest, Hungary
| | - Anna Walter
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Dorottya Gergő
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Department of Pharmacognosy, Semmelweis University, Budapest, Hungary
| | - Fanni Adél Meznerics
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, Budapest, Hungary
| | - Márton Rakovics
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Eötvös Loránd University, Faculty of Social Sciences, Department of Statistics, Budapest, Hungary
| | - Szilárd Váncsa
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - Lajos Vince Kemény
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, Budapest, Hungary
- Department of Physiology, Semmelweis University, Budapest, Hungary
- HCEMM-SU, Translational Dermatology Research Group, Semmelweis University, Budapest, Hungary
| | - Dezső Csupor
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Institute of Clinical Pharmacy, University of Szeged, Szeged, Hungary
| | - Péter Hegyi
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - Michael R. Filbin
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Department of Emergency Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Csaba Varga
- Department of Emergency Medicine, Semmelweis University, Budapest, Hungary
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Bánk G. Fenyves
- Department of Emergency Medicine, Semmelweis University, Budapest, Hungary
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Department of Molecular Biology, Semmelweis University, Budapest, Hungary
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9
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Yang R, Hu C, Zhuo Y, Wang W, Tan Q, Shen Y, Jiang K, Sun X, Xia Q, Deng L. Efficacy and safety of Chinese tonic medicines for treating sepsis or septic shock: a protocol for a systematic review and Bayesian network meta-analysis of randomized controlled trials. Syst Rev 2024; 13:314. [PMID: 39725990 DOI: 10.1186/s13643-024-02736-5] [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: 03/25/2024] [Accepted: 12/09/2024] [Indexed: 12/28/2024] Open
Abstract
BACKGROUND Sepsis is a life-threatening organ dysfunction with high morbidity and mortality. Various studies have demonstrated the effectiveness of Chinese tonic medicines (CTMs) in treating sepsis or septic shock. However, trials directly comparing the efficacy and safety of different CTMs for sepsis or septic shock are still lacking. To identify the most optimal CTM for treating sepsis or septic shock, we plan to perform a systematic review and network meta-analysis of various CTMs used for sepsis or septic shock patients. METHODS Randomized controlled trials (RCTs) that investigated the efficacy and safety of CTMs for patients with sepsis or septic shock will be systematically searched in Pubmed, Embase, Cochrane Central Register of Controlled Trials, Scopus, Web Of Science, CBM, CNKI, Wanfang, and VIP databases from inception to November 2023. The quality of the included studies will be assessed using the Cochrane Risk of Bias V.2.0. tool. The confidence of evidence will be evaluated through the CINeMA (Confidence in Network Meta-Analysis) web application. Primary outcomes include the delta Sequential Organ Failure Assessment (△SOFA) score at day 7 after interventions and 28-day mortality. Secondary outcomes comprise delta serum lactate levels (△Lac) and delta mean arterial pressure (△MAP) at day 7 after interventions as well as total dose and duration of vasoactive drugs. Safety outcome includes adverse drug reactions or adverse drug events (ADRs/ADEs). The Bayesian network meta-analysis will be conducted using the "BUGSnet" package in R version 4.2.2. The surface under the cumulative ranking curve (SUCRA) values will be used to rank each treatment. Statistical inconsistency assessment, publication bias assessment, heterogeneity analysis, sensitivity analysis, and subgroup analysis will be performed. DISCUSSION This study will provide new insights into the efficacy and safety of various CTMs used in sepsis or septic shock patients, providing help for future clinical practice and research. SYSTEMATIC REVIEW REGISTRATION CRD42023482572.
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Affiliation(s)
- Rui Yang
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Cheng Hu
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Yuxin Zhuo
- West China Medical College, Sichuan University, Chengdu, 610041, China
| | - Wen Wang
- Chinese Evidence-Based Medicine Centre, Cochrane China Centreand, MAGIC China Centre, West China Hospital, Sichuan University , Chengdu, 610041, China
| | - Qingyuan Tan
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Yuxin Shen
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Kun Jiang
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xin Sun
- Chinese Evidence-Based Medicine Centre, Cochrane China Centreand, MAGIC China Centre, West China Hospital, Sichuan University , Chengdu, 610041, China
| | - Qing Xia
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China.
| | - Lihui Deng
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China.
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10
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Kim J, Lee SJ, Kim JH, Ahn JY, Jeong SJ, Choi JY, Yeom JS, Oh HJ, Chung YE, Ku NS. Influence of contrast medium on long-term renal function and outcomes in patients with septic acute kidney injury: A propensity-matched cohort study. J Crit Care 2024; 84:154898. [PMID: 39163654 DOI: 10.1016/j.jcrc.2024.154898] [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: 06/13/2024] [Revised: 07/26/2024] [Accepted: 08/10/2024] [Indexed: 08/22/2024]
Abstract
PURPOSE To investigate the relationship between contrast medium administration and long-term mortality and renal function in patients with septic acute kidney injury (AKI). MATERIALS AND METHODS We performed a retrospective, propensity-matched cohort study involving 1521 adult patients admitted with septic shock. Patients with septic AKI who underwent contrast or non-contrast CT scans were enrolled. The primary outcomes were the rates of 90-day mortality and dialysis within 90 days. The secondary outcomes included worsening of AKI, in-hospital mortality, and maintenance of dialysis after 90 days. RESULTS During the study period, 609 patients with septic AKI were identified; 220 (36.1%) underwent contrast CT and 389 (63.9%) underwent non-contrast CT. After propensity score matching, 133 pairs were obtained. There were no significant differences between the contrast and non-contrast CT groups in 90-day mortality (54.9% vs. 58.6%, P = 0.579), dialysis within 90 days (6.8% vs. 8.3%, P = 0.655), worsening AKI (2.3% vs. 3.0%, P = 0.706), in-hospital mortality (10.6% vs. 14.4%, P = 0.369), or maintenance of dialysis after 90 days (0.0% vs. 0.8%, P > 0.99). CONCLUSIONS The administration of intravenous contrast medium was not associated with long-term mortality, deterioration of renal function, or dialysis in patients with septic AKI.
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Affiliation(s)
- Jinnam Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Se Ju Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Internal Medicine, Inha University College of Medicine, Incheon, Republic of Korea
| | - Jung Ho Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; AIDS Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jin Young Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; AIDS Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Su Jin Jeong
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; AIDS Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jun Yong Choi
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; AIDS Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Joon-Sup Yeom
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; AIDS Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hyung Jung Oh
- Division of Nephrology, Sheikh Khalifa Specialty Hospital, Ras Al Khaimah, United Arab Emirates.
| | - Yong Eun Chung
- Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea.
| | - Nam Su Ku
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; AIDS Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
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11
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Liang C, Pan S, Wu W, Chen F, Zhang C, Zhou C, Gao Y, Ruan X, Quan S, Zhao Q, Pan J. Glucocorticoid therapy for sepsis in the AI era: a survey on current and future approaches. Comput Struct Biotechnol J 2024; 24:292-305. [PMID: 38681133 PMCID: PMC11047203 DOI: 10.1016/j.csbj.2024.04.020] [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: 02/05/2024] [Revised: 04/06/2024] [Accepted: 04/07/2024] [Indexed: 05/01/2024] Open
Abstract
Sepsis, a life-threatening medical condition, manifests as new or worsening organ failures due to a dysregulated host response to infection. Many patients with sepsis have manifested a hyperinflammatory phenotype leading to the identification of inflammatory modulation by corticosteroids as a key treatment modality. However, the optimal use of corticosteroids in sepsis treatment remains a contentious subject, necessitating a deeper understanding of their physiological and pharmacological effects. Our study conducts a comprehensive review of randomized controlled trials (RCTs) focusing on traditional corticosteroid treatment in sepsis, alongside an analysis of evolving clinical guidelines. Additionally, we explore the emerging role of artificial intelligence (AI) in medicine, particularly in diagnosing, prognosticating, and treating sepsis. AI's advanced data processing capabilities reveal new avenues for enhancing corticosteroid therapeutic strategies in sepsis. The integration of AI in sepsis treatment has the potential to address existing gaps in knowledge, especially in the application of corticosteroids. Our findings suggest that combining corticosteroid therapy with AI-driven insights could lead to more personalized and effective sepsis treatments. This approach holds promise for improving clinical outcomes and presents a significant advancement in the management of this complex and often fatal condition.
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Affiliation(s)
- Chenglong Liang
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
- Wenzhou Medical University, Wenzhou 325000, China
- School of Nursing, Wenzhou Medical University, Wenzhou 325000, China
| | - Shuo Pan
- Wenzhou Medical University, Wenzhou 325000, China
| | - Wei Wu
- School of Computer Science and Software Engineering, University of Science and Technology Liaoning, Anshan 114051, China
| | - Fanxuan Chen
- Wenzhou Medical University, Wenzhou 325000, China
- School of Biomedical Engineering, School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325000, China
| | - Chengxi Zhang
- School of Materials Science and Engineering, Shandong Jianzhu University, Jinan 250101, China
| | - Chen Zhou
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Yifan Gao
- Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Xiangyuan Ruan
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Shichao Quan
- Department of Big Data in Health Science, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Qi Zhao
- School of Computer Science and Software Engineering, University of Science and Technology Liaoning, Anshan 114051, China
| | - Jingye Pan
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
- Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
- Key Laboratory of Intelligent Treatment and Life Support for Critical Diseases of Zhejiang Province, Wenzhou 325000, China
- Wenzhou Key Laboratory of Critical Care and Artificial Intelligence, Wenzhou 325000, China
- Zhejiang Engineering Research Center for Hospital Emergency and Process Digitization, Wenzhou 325000, China
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12
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Wang L, Wang X. Diagnostic value of multi-parameter ultrasound evaluation in sepsis complicated by acute kidney injury. Ren Fail 2024; 46:2313861. [PMID: 38344995 PMCID: PMC10863507 DOI: 10.1080/0886022x.2024.2313861] [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: 08/10/2023] [Accepted: 01/30/2024] [Indexed: 02/15/2024] Open
Abstract
BACKGROUND This study aimed to discuss the diagnostic value of multi-parameter ultrasound evaluation in sepsis complicated with acute kidney injury (AKI). METHODS Patients were divided into an AKI group (n = 50) and a non-injury group (n = 50) based on the presence of AKI. The clinical characteristics were collected, and renal function parameters between the two groups were compared, including 24-h urine volume, serum creatinine, urea, serum cystatin C (CysC), renal parenchymal thickness (RPT), renal artery resistance index (RI), and multi-parameter ultrasound scoring (MPUS). Additionally, logistic regression analysis was conducted to determine the influencing factors of sepsis complicated with AKI. The prediction value was evaluated using a receiver operating characteristic (ROC) curve. RESULTS In the AKI group, creatinine, CysC, urea, MPUS score, RPT, and RI values were significantly higher, while the 24-h urine volume was lower than those in the non-injury group (p < 0.01). Moreover, multivariate logistic analysis indicated that high CysC and RI values were independent risk factors, whereas high 24-h urine volume and low MPUS were independent protective factors for sepsis-induced AKI. The ROC curve demonstrated that RI (AUC = 0.906) was more effective than 24-h urine volume (AUC = 0.797), CysC (AUC = 0.730), and MPUS (AUC = 0.794) in identifying sepsis-induced AKI. CONCLUSION High RI values increase the risk of sepsis-induced AKI, whereas low MPUS may reduce it. RI showed high diagnosis values for sepsis complicated with AKI.
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Affiliation(s)
- Liu Wang
- Department of Ultrasound Medicine, Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Shiyan, China
| | - Xiang Wang
- Department of Critical Care Medicine, Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Shiyan, China
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13
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Choi Y, Oh S, Huh JW, Joo HT, Lee H, You W, Bae CM, Choi JH, Kim KJ. Deep reinforcement learning extracts the optimal sepsis treatment policy from treatment records. COMMUNICATIONS MEDICINE 2024; 4:245. [PMID: 39578542 PMCID: PMC11584651 DOI: 10.1038/s43856-024-00665-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: 06/02/2023] [Accepted: 11/05/2024] [Indexed: 11/24/2024] Open
Abstract
BACKGROUND Sepsis is one of the most life-threatening medical conditions. Therefore, many clinical trials have been conducted to identify optimal treatment strategies for sepsis. However, finding reliable strategies remains challenging due to limited-scale clinical tests. Here we tried to extract the optimal sepsis treatment policy from accumulated treatment records. METHODS In this study, with our modified deep reinforcement learning algorithm, we stably generated a patient treatment artificial intelligence model. As training data, 16,744 distinct admissions in tertiary hospitals were used and tested with separate datasets. Model performance was tested by t test and visualization of estimated survival rates. We also analyze model behavior using the confusion matrix, important feature extraction by a random forest decision tree, and treatment behavior comparison to understand how our treatment model achieves high performance. RESULTS Here we show that our treatment model's policy achieves a significantly higher estimated survival rate (up to 10.03%). We also show that our models' vasopressor treatment was quite different from that of physicians. Here, we identify that blood urea nitrogen, age, sequential organ failure assessment score, and shock index are the most different factors in dealing with sepsis patients between our model and physicians. CONCLUSIONS Our results demonstrate that the patient treatment model can extract potential optimal sepsis treatment policy. We also extract core information about sepsis treatment by analyzing its policy. These results may not apply directly in clinical settings because they were only tested on a database. However, they are expected to serve as important guidelines for further research.
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Affiliation(s)
- Yunho Choi
- School of Integrated Technology, Gwangju Institute of Science and Technology, Chemdan-gwa-gi-ro, Gwangju, 61005, Republic of Korea
| | - Songmi Oh
- School of Integrated Technology, Gwangju Institute of Science and Technology, Chemdan-gwa-gi-ro, Gwangju, 61005, Republic of Korea
| | - Jin Won Huh
- Pulmonary and Critical Care Medicine, Asan Medical Center, 88 Olympic-ro, Seoul, 05505, Republic of Korea
| | - Ho-Taek Joo
- School of Integrated Technology, Gwangju Institute of Science and Technology, Chemdan-gwa-gi-ro, Gwangju, 61005, Republic of Korea
| | - Hosu Lee
- Department of Control and Robot Engineering, Gyeongsang National University, Jinju-daero, Jinju-si, 52828, Republic of Korea
| | - Wonsang You
- School of Integrated Technology, Gwangju Institute of Science and Technology, Chemdan-gwa-gi-ro, Gwangju, 61005, Republic of Korea
| | - Cheng-Mok Bae
- School of Integrated Technology, Gwangju Institute of Science and Technology, Chemdan-gwa-gi-ro, Gwangju, 61005, Republic of Korea
| | - Jae-Hun Choi
- Medical Information Lab, Electronics and Telecommunications Research Institute, 218 Gajeong-ro, Yuseong-gu, Daejeon, 34129, Republic of Korea
| | - Kyung-Joong Kim
- School of Integrated Technology, Gwangju Institute of Science and Technology, Chemdan-gwa-gi-ro, Gwangju, 61005, Republic of Korea.
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Steppan J, Wang H, Nandakumar K, Gadkari M, Poe A, Pak L, Brady T, Berkowitz DE, Shimoda LA, Santhanam L. LOXL2 inhibition ameliorates pulmonary artery remodeling in pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 2024; 327:L423-L438. [PMID: 39010824 PMCID: PMC11482525 DOI: 10.1152/ajplung.00327.2023] [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: 10/30/2023] [Revised: 06/16/2024] [Accepted: 07/08/2024] [Indexed: 07/17/2024] Open
Abstract
Conduit pulmonary arterial stiffening and the resultant increase in pulmonary vascular impedance have emerged as an important underlying driver of pulmonary arterial hypertension (PAH). Given that matrix deposition is central to vascular remodeling, we evaluated the role of the collagen cross-linking enzyme lysyl oxidase like 2 (LOXL2) in this study. Human pulmonary artery smooth muscle cells (PASMCs) subjected to hypoxia showed increased LOXL2 secretion. LOXL2 activity and expression were markedly higher in primary PASMCs isolated from the pulmonary arteries of the rat Sugen 5416 + hypoxia (SuHx) model of severe pulmonary hypertension (PH). Similarly, LOXL2 protein and mRNA levels were increased in the pulmonary arteries (PA) and lungs of rats with PH (SuHx and monocrotaline (MCT) models). Pulmonary arteries (PAs) isolated from the rats with PH exhibited hypercontractility to phenylephrine and attenuated vasorelaxation elicited by acetylcholine, indicating severe endothelial dysfunction. Tensile testing revealed a significant increase in PA stiffness in PH. Treatment with PAT-1251, a novel small-molecule LOXL2 inhibitor, improved active and passive properties of the PA ex vivo. There was an improvement in right heart function as measured by right ventricular pressure volume loops in vivo with PAT-1251. Importantly, PAT-1251 treatment ameliorated PH, resulting in improved pulmonary artery pressures, right ventricular remodeling, and survival. Hypoxia-induced LOXL2 activation is a causal mechanism in pulmonary artery stiffening in PH and pulmonary artery mechanical and functional decline. LOXL2 inhibition with PAT-1251 could be a promising approach to improve pulmonary artery pressures, right ventricular elastance, cardiac relaxation, and survival in PAH.NEW & NOTEWORTHY Pulmonary arterial stiffening contributes to the progression of PAH and the deterioration of right heart function. This study shows that LOXL2 is upregulated in rat models of PH. LOXL2 inhibition halts pulmonary vascular remodeling and improves PA contractility, endothelial function, and PA pressure, resulting in prolonged survival. Thus, LOXL2 is an important mediator of PA remodeling and stiffening in PH and a promising target to improve PA pressures and survival in PH.
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Affiliation(s)
- Jochen Steppan
- Department of Anesthesiology and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States
| | - Huilei Wang
- Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States
| | - Kavitha Nandakumar
- Department of Anesthesiology and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States
| | - Mahin Gadkari
- Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore Maryland, United States
| | - Alan Poe
- Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States
| | - Lydia Pak
- Department of Molecular and Cellular Biology, Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, Maryland, United States
| | - Travis Brady
- Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States
| | - Dan E Berkowitz
- Department of Anesthesiology and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States
- Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States
| | - Larissa A Shimoda
- Division of Pulmonary and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States
| | - Lakshmi Santhanam
- Department of Anesthesiology and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States
- Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States
- Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore Maryland, United States
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15
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Abdul-Aziz MH, Hammond NE, Brett SJ, Cotta MO, De Waele JJ, Devaux A, Di Tanna GL, Dulhunty JM, Elkady H, Eriksson L, Hasan MS, Khan AB, Lipman J, Liu X, Monti G, Myburgh J, Novy E, Omar S, Rajbhandari D, Roger C, Sjövall F, Zaghi I, Zangrillo A, Delaney A, Roberts JA. Prolonged vs Intermittent Infusions of β-Lactam Antibiotics in Adults With Sepsis or Septic Shock: A Systematic Review and Meta-Analysis. JAMA 2024; 332:638-648. [PMID: 38864162 PMCID: PMC11170459 DOI: 10.1001/jama.2024.9803] [Citation(s) in RCA: 34] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Accepted: 05/07/2024] [Indexed: 06/13/2024]
Abstract
Importance There is uncertainty about whether prolonged infusions of β-lactam antibiotics improve clinically important outcomes in critically ill adults with sepsis or septic shock. Objective To determine whether prolonged β-lactam antibiotic infusions are associated with a reduced risk of death in critically ill adults with sepsis or septic shock compared with intermittent infusions. Data Sources The primary search was conducted with MEDLINE (via PubMed), CINAHL, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from inception to May 2, 2024. Study Selection Randomized clinical trials comparing prolonged (continuous or extended) and intermittent infusions of β-lactam antibiotics in critically ill adults with sepsis or septic shock. Data Extraction and Synthesis Data extraction and risk of bias were assessed independently by 2 reviewers. Certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation approach. A bayesian framework was used as the primary analysis approach and a frequentist framework as the secondary approach. Main Outcomes and Measures The primary outcome was all-cause 90-day mortality. Secondary outcomes included intensive care unit (ICU) mortality and clinical cure. Results From 18 eligible randomized clinical trials that included 9108 critically ill adults with sepsis or septic shock (median age, 54 years; IQR, 48-57; 5961 men [65%]), 17 trials (9014 participants) contributed data to the primary outcome. The pooled estimated risk ratio for all-cause 90-day mortality for prolonged infusions of β-lactam antibiotics compared with intermittent infusions was 0.86 (95% credible interval, 0.72-0.98; I2 = 21.5%; high certainty), with a 99.1% posterior probability that prolonged infusions were associated with lower 90-day mortality. Prolonged infusion of β-lactam antibiotics was associated with a reduced risk of intensive care unit mortality (risk ratio, 0.84; 95% credible interval, 0.70-0.97; high certainty) and an increase in clinical cure (risk ratio, 1.16; 95% credible interval, 1.07-1.31; moderate certainty). Conclusions and Relevance Among adults in the intensive care unit who had sepsis or septic shock, the use of prolonged β-lactam antibiotic infusions was associated with a reduced risk of 90-day mortality compared with intermittent infusions. The current evidence presents a high degree of certainty for clinicians to consider prolonged infusions as a standard of care in the management of sepsis and septic shock. Trial Registration PROSPERO Identifier: CRD42023399434.
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Affiliation(s)
- Mohd H. Abdul-Aziz
- University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Naomi E. Hammond
- Critical Care Program, The George Institute for Global Health and University of New South Wales, Sydney, New South Wales, Australia
- Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, Sydney, New South Wales, Australia
| | - Stephen J. Brett
- Department of Surgery and Cancer, Imperial College, London, United Kingdom
| | - Menino O. Cotta
- University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Jan J. De Waele
- Department of Intensive Care Medicine, Ghent University Hospital, Ghent, Belgium
| | - Anthony Devaux
- Statistics Division, The George Institute for Global Health and University of New South Wales, Sydney, New South Wales, Australia
| | - Gian Luca Di Tanna
- Statistics Division, The George Institute for Global Health and University of New South Wales, Sydney, New South Wales, Australia
- Department of Business Economics, Health and Social Care, University of Applied Sciences and Arts of Southern Switzerland, Manno, Switzerland
- Department of Clinical Research, University of Bern, Bern, Switzerland
| | - Joel M. Dulhunty
- Critical Care Program, The George Institute for Global Health and University of New South Wales, Sydney, New South Wales, Australia
- Department of Intensive Care Medicine, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
- Redcliffe Hospital, Redcliffe, Queensland, Australia
- Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Hatem Elkady
- Department of Intensive Care Medicine, Westmead Hospital, Sydney, New South Wales, Australia
| | - Lars Eriksson
- UQ Library, The University of Queensland, Brisbane, Queensland, Australia
| | - M. Shahnaz Hasan
- Department of Anesthesiology, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
| | - Ayesha Bibi Khan
- Division of Critical Care, University of Witwatersrand, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa
| | - Jeffrey Lipman
- University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
- Department of Intensive Care Medicine, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
- Jamieson Trauma Institute, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
- Division of Anesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France
| | - Xiaoqiu Liu
- Statistics Division, The George Institute for Global Health and University of New South Wales, Sydney, New South Wales, Australia
- School of Population Health, University of New South Wales, Sydney, New South Wales, Australia
| | - Giacomo Monti
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - John Myburgh
- Critical Care Program, The George Institute for Global Health and University of New South Wales, Sydney, New South Wales, Australia
- Department of Intensive Care, St George Hospital, Kogarah, New South Wales, Australia
| | - Emmanuel Novy
- Service d’anesthésie-réanimation et médicine péri-opératoire Brabois adulte, CHRU de Nancy, Nancy, France
- Université de Lorraine, SIMPA, Nancy, France
| | - Shahed Omar
- Division of Critical Care, University of Witwatersrand, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa
| | - Dorrilyn Rajbhandari
- Critical Care Program, The George Institute for Global Health and University of New South Wales, Sydney, New South Wales, Australia
| | - Claire Roger
- Département d’anesthésie et réanimation, douleur et médecine d’urgence, CHU Carémeau, Nîmes, France
- UR UM 103IMAGINE, Faculté de Médecine, Montpellier Université, Nîmes, France
| | - Fredrik Sjövall
- Intensive and Perioperative Care, Skåne University Hospital, Malmö, Sweden
- Department of Clinical Sciences, Lund University, Lund, Sweden
| | - Irene Zaghi
- Department of Diagnostic and Experimental Medicine, University of Bologna, Bologna, Italy
| | - Alberto Zangrillo
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Anthony Delaney
- Critical Care Program, The George Institute for Global Health and University of New South Wales, Sydney, New South Wales, Australia
- Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, Sydney, New South Wales, Australia
| | - Jason A. Roberts
- University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
- Department of Intensive Care Medicine, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
- Division of Anesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France
- Herston Infectious Diseases Institute (HeIDI), Metro North Health, Brisbane, Queensland, Australia
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Zhang H, Lian H, Zhang Q, Zhao H, Wang X. Can central venous pressure help identify acute right ventricular dysfunction in mechanically ventilated critically ill patients? Ann Intensive Care 2024; 14:114. [PMID: 39031301 PMCID: PMC11264666 DOI: 10.1186/s13613-024-01352-9] [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: 05/11/2024] [Accepted: 07/09/2024] [Indexed: 07/22/2024] Open
Abstract
OBJECTIVE To investigate the relationship between central venous pressure (CVP) and acute right ventricular (RV) dysfunction in critically ill patients on mechanical ventilation. METHODS This retrospective study enrolled mechanically ventilated critically ill who underwent transthoracic echocardiographic examination and CVP monitoring. Echocardiographic indices including tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and tricuspid lateral annular systolic velocity wave (S') were collected to assess RV function. Patients were then classified into three groups based on their RV function and presence of systemic venous congestion as assessed by inferior vena cava diameter (IVCD) and hepatic vein (HV) Doppler: normal RV function (TAPSE ≥ 17 mm, FAC ≥ 35% and S' ≥9.5 cm/sec), isolated RV dysfunction (TAPSE < 17 mm or FAC < 35% or S' <9.5 cm/sec with IVCD ≤ 20 mm or HV S ≥ D), and RV dysfunction with congestion (TAPSE < 17 mm or FAC < 35% or S' <9.5 cm/sec with IVCD > 20 mm and HV S < D). RESULTS A total of 518 patients were enrolled in the study, of whom 301 were categorized in normal RV function group, 164 in isolated RV dysfunction group and 53 in RV dysfunction with congestion group. Receiver operating characteristic analysis revealed a good discriminative ability of CVP for identifying patients with RV dysfunction and congestion(AUC 0.839; 95% CI: 0.795-0.883; p < 0.001). The optimal CVP cutoff was 10 mm Hg, with sensitivity of 79.2%, specificity of 69.4%, negative predictive value of 96.7%, and positive predictive value of 22.8%. A large gray zone existed between 9 mm Hg and 12 mm Hg, encompassing 95 patients (18.3%). For identifying all patients with RV dysfunction, CVP demonstrated a lower discriminative ability (AUC 0.616; 95% CI: 0.567-0.665; p < 0.001). Additionally, the gray zone was even larger, ranging from 5 mm Hg to 12 mm Hg, and included 349 patients (67.4%). CONCLUSIONS CVP may be a helpful indicator of acute RV dysfunction patients with systemic venous congestion in mechanically ventilated critically ill, but its accuracy is limited. A CVP less than10 mm Hg can almost rule out RV dysfunction with congestion. In contrast, CVP should not be used to identify general RV dysfunction.
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Affiliation(s)
- Hongmin Zhang
- Department of Health Care, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1# Shuai Fu Yuan, Dong Cheng District, Beijing, 100730, China.
| | - Hui Lian
- Department of Health Care, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1# Shuai Fu Yuan, Dong Cheng District, Beijing, 100730, China
| | - Qing Zhang
- Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1# Shuai Fu Yuan, Dong Cheng District, Beijing, 100730, China
| | - Hua Zhao
- Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1# Shuai Fu Yuan, Dong Cheng District, Beijing, 100730, China
| | - Xiaoting Wang
- Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1# Shuai Fu Yuan, Dong Cheng District, Beijing, 100730, China
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17
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Liu Y, Hu S, Shi B, Yu B, Luo W, Peng S, Du X. The Role of Iron Metabolism in Sepsis-associated Encephalopathy: a Potential Target. Mol Neurobiol 2024; 61:4677-4690. [PMID: 38110647 DOI: 10.1007/s12035-023-03870-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Accepted: 11/30/2023] [Indexed: 12/20/2023]
Abstract
Sepsis-associated encephalopathy (SAE) is an acute cerebral dysfunction secondary to infection, and the severity can range from mild delirium to deep coma. Disorders of iron metabolism have been proven to play an important role in a variety of neurodegenerative diseases by inducing cell damage through iron accumulation in glial cells and neurons. Recent studies have found that iron accumulation is also a potential mechanism of SAE. Systemic inflammation can induce changes in the expression of transporters and receptors on cells, especially high expression of divalent metal transporter1 (DMT1) and low expression of ferroportin (Fpn) 1, which leads to iron accumulation in cells. Excessive free Fe2+ can participate in the Fenton reaction to produce reactive oxygen species (ROS) to directly damage cells or induce ferroptosis. As a result, it may be of great help to improve SAE by treatment of targeting disorders of iron metabolism. Therefore, it is important to review the current research progress on the mechanism of SAE based on iron metabolism disorders. In addition, we also briefly describe the current status of SAE and iron metabolism disorders and emphasize the therapeutic prospect of targeting iron accumulation as a treatment for SAE, especially iron chelator. Moreover, drug delivery and side effects can be improved with the development of nanotechnology. This work suggests that treating SAE based on disorders of iron metabolism will be a thriving field.
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Affiliation(s)
- Yinuo Liu
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China
- The Clinical Medical College of Nanchang University, Nanchang, 330006, Jiangxi, China
| | - Shengnan Hu
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China
- The Clinical Medical College of Nanchang University, Nanchang, 330006, Jiangxi, China
| | - Bowen Shi
- The Clinical Medical College of Nanchang University, Nanchang, 330006, Jiangxi, China
| | - Bodong Yu
- The Clinical Medical College of Nanchang University, Nanchang, 330006, Jiangxi, China
| | - Wei Luo
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Shengliang Peng
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.
| | - Xiaohong Du
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.
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18
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Feng Y, Zhang M, Jia SY, Guo YX, Jia X. Dexamethasone alleviates etomidate-induced myoclonus by reversing the inhibition of excitatory amino acid transporters. Front Neurosci 2024; 18:1399653. [PMID: 38979126 PMCID: PMC11228700 DOI: 10.3389/fnins.2024.1399653] [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: 03/12/2024] [Accepted: 05/27/2024] [Indexed: 07/10/2024] Open
Abstract
Background Etomidate can induce myoclonus with an incidence of 50 ~ 85% during anesthesia induction. Dexamethasone, as a long-acting synthetic glucocorticoid, has neuroprotective effects. However, the effects of dexamethasone on the etomidate-induced myoclonus remain uncertain. Methods Adult male Sprague-Dawley rats were randomly assigned to receive etomidate (1.5 mg/kg) plus dexamethasone (4 mg/kg) (etomidate plus dexamethasone group) or etomidate (1.5 mg/kg) plus the same volume of normal saline (NS) (etomidate plus NS group). The mean behavioral scores, local field potentials and muscular tension were recorded to explore the effects of dexamethasone on etomidate-induced myoclonus. Liquid chromatography coupled with tandem mass spectrometric system (LC-MS/MS), quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting were applied to analyze the levels of glutamate and γ-aminobutyric acid (GABA), the mRNA and protein expression of excitatory amino acid transporters (EAATs), and plasma corticosterone levels at different time points after anesthesia. Results Compared with the etomidate plus NS treatment, the etomidate plus dexamethasone treatment significantly decreased the mean behavioral score at 1, 3, 4, and 5 min after administration; the peak power spectral density (PSD) (p = 0.0197) in the analysis of ripple waves; and the glutamate level (p = 0.0139) in the neocortex. However, compared with etomidate plus NS, etomidate plus dexamethasone increased the expression of the neocortical proteins of EAAT1 (p = 0.0207) and EAAT2 (p = 0.0022) and aggravated the inhibition of corticosterone at 4 h (p = 0.0019), 5 h (p = 0.0041), and 6 h (p = 0.0009) after administration. Conclusion Dexamethasone can attenuate the myoclonus, inhibit the glutamate accumulation, and reverse the suppression of EAATs in the neocortex induced by etomidate following myoclonus, while conversely aggravating etomidate-induced adrenal suppression.
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Affiliation(s)
- Yan Feng
- Department of Anesthesiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
- Department of Anesthesiology, Sichuan Integrative Medicine Hospital, Chengdu, China
| | - Min Zhang
- Department of Anesthesiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Shuai-Ying Jia
- Department of Anesthesiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Yan-Xia Guo
- Department of Anesthesiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Xue Jia
- Department of Anesthesiology, Sichuan Integrative Medicine Hospital, Chengdu, China
- Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China
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Zhang Z, Guo L, Jia L, Duo H, Shen L, Zhao H. Factors contributing to sepsis-associated encephalopathy: a comprehensive systematic review and meta-analysis. Front Med (Lausanne) 2024; 11:1379019. [PMID: 38835794 PMCID: PMC11148246 DOI: 10.3389/fmed.2024.1379019] [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: 01/30/2024] [Accepted: 05/07/2024] [Indexed: 06/06/2024] Open
Abstract
Background This study aims to systematically assess the risk factors, the overall strength of association, and evidence quality related to sepsis-associated encephalopathy. Methods A systematic search was conducted in the Cochrane Library, PubMed, Web of Science, and Embase for cohort or case-control studies published up to August 2023 on risk factors associated with sepsis-related encephalopathy. The selected studies were screened, data were extracted, and the quality was evaluated using the Newcastle-Ottawa Scale. Meta-analysis was performed using RevMan 5.3 software. The certainty of the evidence was assessed using the GRADE criteria. Results A total of 13 studies involving 1,906 participants were included in the analysis. Among these studies, 12 were of high quality, and one was of moderate quality. Our meta-analysis identified six risk factors significantly associated with Serious Adverse Events (SAE). These included APACHE II, SOFA, age, tau protein, and IL-6, which were found to be risk factors with significant effects (standard mean difference SMD: 1.24-2.30), and albumin, which was a risk factor with moderate effects (SMD: -0.55). However, the certainty of evidence for the risk factors identified in this meta-analysis ranged from low to medium. Conclusion This systematic review and meta-analysis identified several risk factors with moderate to significant effects. APACHE II, SOFA, age, tau protein, IL-6, and albumin were associated with sepsis-related encephalopathy and were supported by medium- to high-quality evidence. These findings provide healthcare professionals with an evidence-based foundation for managing and treating hospitalized adult patients with sepsis-related encephalopathy.
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Affiliation(s)
- Zhiyang Zhang
- Department of Critical Care Medicine, Hebei Medical University, Shijiazhuang, China
- Department of Intensive Care Unit, Hebei General Hospital, Shijiazhuang, China
| | - Li Guo
- Department of Neonatal, Shijiazhuang Fourth Hospital, Shijiazhuang, China
| | - Lijing Jia
- Department of Intensive Care Unit, Hebei General Hospital, Shijiazhuang, China
| | - Hong Duo
- Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Limin Shen
- Department of Intensive Care Unit, Hebei General Hospital, Shijiazhuang, China
| | - Heling Zhao
- Department of Critical Care Medicine, Hebei Medical University, Shijiazhuang, China
- Department of Intensive Care Unit, Hebei General Hospital, Shijiazhuang, China
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Meng J, Li X, Xiao Y, Tang H, Liu P, Wu Y, Xiong Y, Gao S. Intensive or liberal glucose control in intensive care units for septic patients? A meta-analysis of randomized controlled trials. Diabetes Metab Syndr 2024; 18:103045. [PMID: 38796958 DOI: 10.1016/j.dsx.2024.103045] [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: 12/19/2023] [Revised: 05/21/2024] [Accepted: 05/22/2024] [Indexed: 05/29/2024]
Abstract
OBJECTIVE To compare the clinical outcomes of intensive glucose control and liberal glucose control for septic patients in intensive care unit. METHODS The databases of PubMed, Cochrane Library, Embase and Web of Science were searched systematically from inception to November 27, 2023 to identify trials involving a randomized comparison between intensive and liberal glucose control for septic patients in intensive care unit. RESULTS A total of 14 randomized controlled trials involving 6226 patients were finally included. There was no statistically significant difference observed between intensive glucose control and liberal glucose control in terms of all-cause mortality, the need for renal replacement, vasopressor-free and mechanical ventilation-free days, and length of hospital stay. However, it is noteworthy that intensive glucose control exhibited a statistically higher risk of severe hypoglycemia (RR 2.66; 95%CI 1.85 to 3.83), need for blood transfusion (RR 1.12; 95%CI 1.01 to 1.23), and statistically prolonged length of stay in the ICU (MD 1.67; 95%CI 0.22 to 3.12) compared to liberal glucose control. Nevertheless, sensitivity analysis revealed that the need for blood transfusion and length of stay in the intensive care unit were not robust. CONCLUSIONS Both intensive and liberal glucose control had comparable effects on improving patient outcomes, but intensive glucose control carried a higher risk of severe hypoglycemia.
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Affiliation(s)
- Jiahao Meng
- Department of Orthopaedics, Xiangya Hospital Central South University, #87 Xiangya Road, Changsha, 410008, Hunan, China
| | - Xi Li
- Department of Orthopaedics, Xiangya Hospital Central South University, #87 Xiangya Road, Changsha, 410008, Hunan, China
| | - Yifan Xiao
- Department of Orthopaedics, Xiangya Hospital Central South University, #87 Xiangya Road, Changsha, 410008, Hunan, China
| | - Hang Tang
- Department of Orthopaedics, Xiangya Hospital Central South University, #87 Xiangya Road, Changsha, 410008, Hunan, China
| | - Pan Liu
- Department of Orthopaedics, Xiangya Hospital Central South University, #87 Xiangya Road, Changsha, 410008, Hunan, China
| | - Yumei Wu
- Department of Orthopaedics, Xiangya Hospital Central South University, #87 Xiangya Road, Changsha, 410008, Hunan, China
| | - Yilin Xiong
- Department of Orthopaedics, Xiangya Hospital Central South University, #87 Xiangya Road, Changsha, 410008, Hunan, China
| | - Shuguang Gao
- Department of Orthopaedics, Xiangya Hospital Central South University, #87 Xiangya Road, Changsha, 410008, Hunan, China; Hunan Key Laboratory of Joint Degeneration and Injury, Changsha, Hunan, China; Hunan Engineering Research Center of Osteoarthritis, Changsha, Hunan, China; National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
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21
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Fuchs C, Scheer CS, Wauschkuhn S, Vollmer M, Meissner K, Hahnenkamp K, Gründling M, Selleng S, Thiele T, Borgstedt R, Kuhn SO, Rehberg S, Scholz SS. Continuation of chronic antiplatelet therapy is not associated with increased need for transfusions: a cohort study in critically ill septic patients. BMC Anesthesiol 2024; 24:146. [PMID: 38627682 PMCID: PMC11022363 DOI: 10.1186/s12871-024-02516-7] [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: 08/25/2023] [Accepted: 03/28/2024] [Indexed: 04/19/2024] Open
Abstract
BACKGROUND The decision to maintain or halt antiplatelet medication in septic patients admitted to intensive care units presents a clinical dilemma. This is due to the necessity to balance the benefits of preventing thromboembolic incidents and leveraging anti-inflammatory properties against the increased risk of bleeding. METHODS This study involves a secondary analysis of data from a prospective cohort study focusing on patients diagnosed with severe sepsis or septic shock. We evaluated the outcomes of 203 patients, examining mortality rates and the requirement for transfusion. The cohort was divided into two groups: those whose antiplatelet therapy was sustained (n = 114) and those in whom it was discontinued (n = 89). To account for potential biases such as indication for antiplatelet therapy, propensity score matching was employed. RESULTS Therapy continuation did not significantly alter transfusion requirements (discontinued vs. continued in matched samples: red blood cell concentrates 51.7% vs. 68.3%, p = 0.09; platelet concentrates 21.7% vs. 18.3%, p = 0.82; fresh frozen plasma concentrates 38.3% vs. 33.3%, p = 0.7). 90-day survival was higher within the continued group (30.0% vs. 70.0%; p < 0.001) and the Log-rank test (7-day survivors; p = 0.001) as well as Cox regression (both matched samples) suggested an association between continuation of antiplatelet therapy < 7 days and survival (HR: 0.24, 95%-CI 0.10 to 0.63, p = 0.004). Sepsis severity expressed by the SOFA score did not differ significantly in matched and unmatched patients (both p > 0.05). CONCLUSIONS The findings suggest that continuing antiplatelet therapy in septic patients admitted to intensive care units could be associated with a significant survival benefit without substantially increasing the need for transfusion. These results highlight the importance of a nuanced approach to managing antiplatelet medication in the context of severe sepsis and septic shock.
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Affiliation(s)
- Christian Fuchs
- Department of Anaesthesiology, University Medicine Greifswald, Greifswald, Germany
| | - Christian S Scheer
- Department of Anaesthesiology, University Medicine Greifswald, Greifswald, Germany
| | - Steffi Wauschkuhn
- Department of Psychosomatic Medicine and Psychotherapy, Ernst von Bergmann Hospital, Potsdam, Germany
| | - Marcus Vollmer
- Institute of Bioinformatics, University Medicine Greifswald, Greifswald, Germany
| | - Konrad Meissner
- Department of Anaesthesiology, University Medical Center Göttingen, Göttingen, Germany
| | - Klaus Hahnenkamp
- Department of Anaesthesiology, University Medicine Greifswald, Greifswald, Germany
| | - Matthias Gründling
- Department of Anaesthesiology, University Medicine Greifswald, Greifswald, Germany
| | - Sixten Selleng
- Department of Anaesthesiology, University Medicine Greifswald, Greifswald, Germany
| | - Thomas Thiele
- Institute of Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany
| | - Rainer Borgstedt
- Department of Anaesthesiology, Intensive Care, Emergency Medicine, Transfusion Medicine and Pain Therapy, Medical School, Protestant Hospital of the Bethel Foundation, Bielefeld University, University Medical Center OWL, Burgsteig 13, 33617, Bielefeld, Germany
| | - Sven-Olaf Kuhn
- Department of Anaesthesiology, University Medicine Greifswald, Greifswald, Germany
| | - Sebastian Rehberg
- Department of Anaesthesiology, Intensive Care, Emergency Medicine, Transfusion Medicine and Pain Therapy, Medical School, Protestant Hospital of the Bethel Foundation, Bielefeld University, University Medical Center OWL, Burgsteig 13, 33617, Bielefeld, Germany
| | - Sean Selim Scholz
- Department of Anaesthesiology, Intensive Care, Emergency Medicine, Transfusion Medicine and Pain Therapy, Medical School, Protestant Hospital of the Bethel Foundation, Bielefeld University, University Medical Center OWL, Burgsteig 13, 33617, Bielefeld, Germany.
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Morabito LA, Corica D, Pepe G, Li Pomi A, Aversa T, Wasniewska MG. Critical illness-related corticosteroid insufficiency (CIRCI) in paediatric patients: a diagnostic and therapeutic challenge. Ital J Pediatr 2024; 50:46. [PMID: 38462639 PMCID: PMC10926569 DOI: 10.1186/s13052-024-01616-x] [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: 11/09/2023] [Accepted: 02/24/2024] [Indexed: 03/12/2024] Open
Abstract
Critical illness-related corticosteroid insufficiency or CIRCI is characterized by acute and life-threatening disfunction of hypothalamic-pituitary-adrenal (HPA) axis observed among intensive care unit- staying patients.It is associated with increased circulating levels of biological markers of inflammation and coagulation, morbidity, length of ICU stay, and mortality.Several mechanisms are involved in CIRCI pathogenesis: reduced CRH-stimulated ACTH release, peripheral resistance to glucocorticoids, altered cortisol synthesis, impaired cortisol-free fraction and bioavailability.Diagnostic and therapeutic management of this condition in children is still debated, probably because of the lack of agreement among intensive care specialists and endocrinologists regarding diagnostic criteria and prevalence of CIRCI in paediatric age.In the present narrative review, we focused on definition of CIRCI in paediatric age and we advise on how to diagnose and treat this poorly understood condition, based on current literature data.
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Affiliation(s)
- Letteria Anna Morabito
- Pediatric Unit, Maternal Infant Department, "Gaetano Martino" University Hospital, Via Consolare Valeria, 98122, Messina, Italy.
| | - Domenico Corica
- Pediatric Unit, Maternal Infant Department, "Gaetano Martino" University Hospital, Via Consolare Valeria, 98122, Messina, Italy
- Department of Human Pathology in Adulthood and Childhood, University of Messina, Messina, Italy
| | - Giorgia Pepe
- Pediatric Unit, Maternal Infant Department, "Gaetano Martino" University Hospital, Via Consolare Valeria, 98122, Messina, Italy
- Department of Human Pathology in Adulthood and Childhood, University of Messina, Messina, Italy
| | - Alessandra Li Pomi
- Department of Human Pathology in Adulthood and Childhood, University of Messina, Messina, Italy
| | - Tommaso Aversa
- Pediatric Unit, Maternal Infant Department, "Gaetano Martino" University Hospital, Via Consolare Valeria, 98122, Messina, Italy
- Department of Human Pathology in Adulthood and Childhood, University of Messina, Messina, Italy
| | - Malgorzata Gabriela Wasniewska
- Pediatric Unit, Maternal Infant Department, "Gaetano Martino" University Hospital, Via Consolare Valeria, 98122, Messina, Italy
- Department of Human Pathology in Adulthood and Childhood, University of Messina, Messina, Italy
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Li N, Ren P, Wang J, Zhu X, Qiao X, Zeng Z, Ye T, Wang S, Meng Z, Gan H, Liu S, Sun Y, Zhu X, Dou G, Gu R. Immune-Related Molecules CD3G and FERMT3: Novel Biomarkers Associated with Sepsis. Int J Mol Sci 2024; 25:749. [PMID: 38255822 PMCID: PMC10815248 DOI: 10.3390/ijms25020749] [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: 11/08/2023] [Revised: 12/23/2023] [Accepted: 12/31/2023] [Indexed: 01/24/2024] Open
Abstract
Sepsis ranks among the most common health problems worldwide, characterized by organ dysfunction resulting from infection. Excessive inflammatory responses, cytokine storms, and immune-induced microthrombosis are pivotal factors influencing the progression of sepsis. Our objective was to identify novel immune-related hub genes for sepsis through bioinformatic analysis, subsequently validating their specificity and potential as diagnostic and prognostic biomarkers in an animal experiment involving a sepsis mice model. Gene expression profiles of healthy controls and patients with sepsis were obtained from the Gene Expression Omnibus (GEO) and analysis of differentially expressed genes (DEGs) was conducted. Subsequently, weighted gene co-expression network analysis (WGCNA) was used to analyze genes within crucial modules. The functional annotated DEGs which related to the immune signal pathways were used for constructing protein-protein interaction (PPI) analysis. Following this, two hub genes, FERMT3 and CD3G, were identified through correlation analyses associated with sequential organ failure assessment (SOFA) scores. These two hub genes were associated with cell adhesion, migration, thrombosis, and T-cell activation. Furthermore, immune infiltration analysis was conducted to investigate the inflammation microenvironment influenced by the hub genes. The efficacy and specificity of the two hub genes were validated through a mice sepsis model study. Concurrently, we observed a significant negative correlation between the expression of CD3G and IL-1β and GRO/KC. These findings suggest that these two genes probably play important roles in the pathogenesis and progression of sepsis, presenting the potential to serve as more stable biomarkers for sepsis diagnosis and prognosis, deserving further study.
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Affiliation(s)
- Nanxi Li
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China
| | - Peng Ren
- Beijing Institute of Basic Medical Sciences, Beijing 100850, China
| | - Jingya Wang
- Beijing Institute of Basic Medical Sciences, Beijing 100850, China
| | - Xiaohui Zhu
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China
| | - Xuan Qiao
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China
| | - Zhirui Zeng
- Guizhou Provincial Key Laboratory of Pathogenesis & Drug Research on Common Chronic Diseases, Department of Physiology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550000, China
| | - Tong Ye
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China
| | - Shanshan Wang
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China
| | - Zhiyun Meng
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China
| | - Hui Gan
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China
| | - Shuchen Liu
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China
| | - Yunbo Sun
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China
| | - Xiaoxia Zhu
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China
| | - Guifang Dou
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China
| | - Ruolan Gu
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China
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Chudow MB, Condeni MS, Dhar S, Heavner MS, Nei AM, Bissell BD. Current Practice Review in the Management of Acute Respiratory Distress Syndrome. J Pharm Pract 2023; 36:1454-1471. [PMID: 35728076 DOI: 10.1177/08971900221108713] [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: 12/15/2022]
Abstract
Acute respiratory distress syndrome (ARDS) presents as an acute inflammatory lung injury characterized by refractory hypoxemia and non-cardiac pulmonary edema. An estimated 10% of patients in the intensive care unit and 25% of those who are mechanically ventilated are diagnosed with ARDS. Increased awareness is warranted as mortality rates remain high and delays in diagnosing ARDS are common. The COVID-19 pandemic highlights the importance of understanding ARDS management. Treatment of ARDS can be challenging due to the complexity of the disease state and conflicting existing evidence. Therefore, it is imperative that pharmacists understand both pharmacologic and non-pharmacologic treatment strategies to optimize patient care. This narrative review provides a critical evaluation of current literature describing management practices for ARDS. A review of treatment modalities and supportive care strategies will be presented.
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Affiliation(s)
- Melissa B Chudow
- Department of Pharmacotherapeutics and Clinical Research, University of South Florida Taneja College of Pharmacy, Tampa, FL, USA
| | - Melanie S Condeni
- MUSC College of Pharmacy, Medical University of South Carolina, Charleston, SC, USA
| | - Sanjay Dhar
- Pulmonary Critical Care Ultrasound and Research, Pulmonary and Critical Care Fellowship Program, Division of Pulmonary, Critical Care & Sleep Medicine, University of Kentucky, Lexington, KY, USA
| | - Mojdeh S Heavner
- Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy, Baltimore, MD, USA
| | - Andrea M Nei
- Mayo Clinic College of Medicine & Science, Critical Care Pharmacist, Department of Pharmacy, Mayo Clinic Hospital, Rochester, MN, USA
| | - Brittany D Bissell
- Department of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington, KY, USA
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Cutuli SL, Carelli S, Cascarano L, Cicconi S, Silvestri D, Cicetti M, Vallecoccia MS, Pintaudi G, Tanzarella ES, Grieco DL, Antonelli M, De Pascale G. Clinical implications of endotoxin activity and Polymyxin-B hemoperfusion in critically ill patients with septic cardiomyopathy: A single-center, retrospective, observational study. Artif Organs 2023; 47:1865-1873. [PMID: 37737449 DOI: 10.1111/aor.14645] [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: 05/22/2023] [Revised: 08/21/2023] [Accepted: 09/05/2023] [Indexed: 09/23/2023]
Abstract
BACKGROUND To explore the association between endotoxin activity (EA) and septic cardiomyopathy (SCM), the relationship between endotoxin removal by Polymyxin-B hemoperfusion (PMX-HP) and recovery from SCM (R-SCM), and the correlation between R-SCM and the 28-day mortality in septic patients admitted to the intensive care unit (ICU). METHODS Observational study that included patients admitted to two ICUs of a tertiary university hospital between April 2011 and December 2019, who received PMX-HP for sepsis/septic shock. The SCM and R-SCM were assessed by transthoracic echocardiography. RESULTS Among 148 patients, SCM was diagnosed in 60 (46%) of them and had no relationship with median EA (SCM group: 0.73; no-SCM group: 0.66, p = 0.48). Recovery from SCM was observed in 24 patients (49%) and was independently associated with the PMX-HP (OR 4.19, 95%CI [1.22, 14.3]; p = 0.02) and the SAPS2 II score (OR 0.94, 95%CI [0.9, 0.98]; p = 0.006). In the SCM group, the 28-day mortality was 60% and was independently predicted by R-SCM (OR 0.02, 95%CI [0.001, 0.3] p = 0.005) and SAPS II score (OR 1.11, 95%CI [1.01, 1.23] p = 0.037). CONCLUSIONS In septic patients, EA was not associated with SCM. However, endotoxin removal by Polymyxin-B hemoperfusion was associated with recovery from cardiomyopathy, which was a predictor of lower 28-day mortality.
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Affiliation(s)
- Salvatore Lucio Cutuli
- Department of Emergency, Intensive Care Medicine and Anesthesiology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Institute of Anesthesiology and Intensive Care Medicine, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Simone Carelli
- Department of Emergency, Intensive Care Medicine and Anesthesiology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Institute of Anesthesiology and Intensive Care Medicine, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Laura Cascarano
- Department of Emergency, Intensive Care Medicine and Anesthesiology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Institute of Anesthesiology and Intensive Care Medicine, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Sandra Cicconi
- Department of Anesthesiology and Intensive Care Medicine, Infermi Hospital, Rimini, Italy
| | - Davide Silvestri
- Department of Anesthesiology and Intensive Care Medicine, S. Luca Hospital, Lucca, Italy
| | - Marta Cicetti
- Department of Emergency, Intensive Care Medicine and Anesthesiology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Institute of Anesthesiology and Intensive Care Medicine, Università Cattolica del Sacro Cuore, Rome, Italy
| | | | - Gabriele Pintaudi
- Department of Emergency, Intensive Care Medicine and Anesthesiology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Institute of Anesthesiology and Intensive Care Medicine, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Eloisa Sofia Tanzarella
- Department of Emergency, Intensive Care Medicine and Anesthesiology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Institute of Anesthesiology and Intensive Care Medicine, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Domenico Luca Grieco
- Department of Emergency, Intensive Care Medicine and Anesthesiology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Institute of Anesthesiology and Intensive Care Medicine, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Massimo Antonelli
- Department of Emergency, Intensive Care Medicine and Anesthesiology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Institute of Anesthesiology and Intensive Care Medicine, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Gennaro De Pascale
- Department of Emergency, Intensive Care Medicine and Anesthesiology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Institute of Anesthesiology and Intensive Care Medicine, Università Cattolica del Sacro Cuore, Rome, Italy
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Ansari MA, Das S, Rai G, Singh PK, Lahan S, Tyagi A, Alamer E, Dar SA. Low monocytic HLA-DR expression in critically ill patients of sepsis: An indicator for antimicrobial and/or immunomodulatory intervention. Transpl Immunol 2023; 81:101942. [PMID: 37866671 DOI: 10.1016/j.trim.2023.101942] [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: 08/26/2023] [Revised: 10/10/2023] [Accepted: 10/19/2023] [Indexed: 10/24/2023]
Abstract
BACKGROUND Sepsis is a result of suppressed host immune response which leads to fatal multi-organ dysfunctionality. Low frequency of active monocytes or reduced expression of human leukocyte antigen (HLA)-DR on monocytes shows the suppressed immune response in sepsis patients. One of the well-studied markers in patients with sepsis is procalcitonin (PCT). The role of monocytic (m) HLA-DR expression has been monitored in sepsis and is being considered a marker of the severity of interim immuno-depression in these patients. The study describes the impact of HLA-DR expression on monocytes quantitatively using flow cytometry. METHODS In this prospective study, we quantified monocytes and their HLA-DR expression in 20 patients of sepsis admitted to the Intensive Care Unit (ICU). Serum levels of PCT and interleukin (IL)-6 production were also measured in these patients, and the results were compared with those in healthy controls. RESULTS Monocyte frequency calculated was higher in sepsis patients as compared to healthy controls, however, HLA-DR expressing monocytes were significantly reduced as was the mean fluorescence intensity (MFI) of HLA-DR. Contrastingly, IL-6 and PCT levels were significantly high in sepsis than controls. The results suggest that low HLA-DR expression, combined with PCT, is a better prognostic parameter in the early phase of sepsis. CONCLUSION Poor recovery of mHLA-DR may serve as an early guide for clinicians to assess the prognosis of sepsis patients and consider immunomodulatory therapy in its management.
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Affiliation(s)
- Mohammad Ahmad Ansari
- Department of Microbiology, University College of Medical Sciences (University of Delhi) & GTB Hospital, Delhi 110095, India
| | - Shukla Das
- Department of Microbiology, University College of Medical Sciences (University of Delhi) & GTB Hospital, Delhi 110095, India.
| | - Gargi Rai
- Department of Microbiology, University College of Medical Sciences (University of Delhi) & GTB Hospital, Delhi 110095, India
| | - Praveen Kumar Singh
- Department of Microbiology, University College of Medical Sciences (University of Delhi) & GTB Hospital, Delhi 110095, India
| | - Shubham Lahan
- University College of Medical Sciences (University of Delhi) & GTB Hospital, Delhi 110095, India
| | - Asha Tyagi
- Department of Anesthesiology and Critical Care, University College of Medical Sciences (University of Delhi) & GTB Hospital, Delhi 110095, India
| | - Edrous Alamer
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan 45142, Saudi Arabia
| | - Sajad Ahmad Dar
- Department of Microbiology, University College of Medical Sciences (University of Delhi) & GTB Hospital, Delhi 110095, India; Research and Scientific Studies Unit, College of Nursing, Jazan University, Jazan 45142, Saudi Arabia.
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Zhang Y, Xu G, Miao F, Huang W, Wang H, Wang X. Insights into the epidemiology, risk factors, and clinical outcomes of carbapenem-resistant Acinetobacter baumannii infections in critically ill children. Front Public Health 2023; 11:1282413. [PMID: 38098829 PMCID: PMC10720883 DOI: 10.3389/fpubh.2023.1282413] [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: 08/24/2023] [Accepted: 11/13/2023] [Indexed: 12/17/2023] Open
Abstract
Background and aims Carbapenem-resistant Acinetobacter baumannii (CRAB) has become a leading cause of nosocomial infections with an increasing impact on critically ill patients, yet there is limited data on contributing factors. This study was aim to evaluate the prevalence and risk factors, and clinical outcomes of CRAB infections among critically ill children in a tertiary university teaching hospital in China. Methods From January 2016 to December 2021, all children diagnosed with nosocomial Acinetobacter baumannii (A. baumannii) infections in the pediatric intensive care unit (PICU) were identified through the computerized microbiology laboratory databases. Among them, children suffering from CRAB infection were designated as a case group, while children with carbapenem susceptible A. baumannii (CSAB) infection were assigned to a control group. This retrospective case-control study was based on two groups of patients to determine potential clinical factors contributing to CRAB infection and death among critically ill children via univariate and multivariate analyses. Results During the 6-year study period, a total of 372 episodes of nosocomial A. baumannii infection in the PICU were eligible and included in the study. These isolates displayed moderate or high rates of resistance to all tested antimicrobials except colistin. The overall prevalence of CRAB and MDRAB (multidrug-resistant A. baumannii) was 78.0% and 80.9%, respectively. Several risk factors found to significantly increase CRAB infection included receiving invasive operation (OR = 9.412, p = 0.001), gastric intubation (OR = 2.478, p = 0.026), prior carbapenems exposure (OR = 2.543, p = 0.003), severe pneumonia (OR = 3.235, p = 0.001), and hemoglobin <110g/L (OR = 3.049, p = 0.005). Of 372 patients with CRAB infection, the mortality rate was 30.9% (115/372) and mortality did not differ between children with CRAB and CSAB infections. Septic shock (OR = 2.992, p = 0.001), AST > 46U/L (OR = 2.015, p = 0.005), bone marrow aspiration (OR = 2.704, p = 0.008), lymphocyte <20 % (OR = 1.992, p = 0.006) and age (OR = 1.094, p = 0.002) were independent risk factors for the death of A. baumanni infection. Conclusions This study highlights considerable incidence rate and remarkable mortality of children with A. baumanni (especially CRAB) infections, and identifies age-specific risk factors for CRAB infection and mortality in critically ill children. These risk factors should be taken into account in pediatric hospitals in order to establish early intervention and rational treatment to improve clinical outcomes.
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Affiliation(s)
- Yufei Zhang
- Department of Clinical Laboratory, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Guifeng Xu
- Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Fei Miao
- Department of Dermatology, Huadong Hospital, Fudan University, Shanghai, China
| | - Weichun Huang
- Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Haiying Wang
- Department of Clinical Laboratory, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xing Wang
- Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China
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Kotani Y, Turi S, Ortalda A, Baiardo Redaelli M, Marchetti C, Landoni G, Bellomo R. Positive single-center randomized trials and subsequent multicenter randomized trials in critically ill patients: a systematic review. Crit Care 2023; 27:465. [PMID: 38017475 PMCID: PMC10685543 DOI: 10.1186/s13054-023-04755-5] [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: 09/12/2023] [Accepted: 11/21/2023] [Indexed: 11/30/2023] Open
Abstract
BACKGROUND It is unclear how often survival benefits observed in single-center randomized controlled trials (sRCTs) involving critically ill patients are confirmed by subsequent multicenter randomized controlled trials (mRCTs). We aimed to perform a systemic literature review of sRCTs with a statistically significant mortality reduction and to evaluate whether subsequent mRCTs confirmed such reduction. METHODS We searched PubMed for sRCTs published in the New England Journal of Medicine, JAMA, or Lancet, from inception until December 31, 2016. We selected studies reporting a statistically significant mortality decrease using any intervention (drug, technique, or strategy) in adult critically ill patients. We then searched for subsequent mRCTs addressing the same research question tested by the sRCT. We compared the concordance of results between sRCTs and mRCTs when any mRCT was available. We registered this systematic review in the PROSPERO International Prospective Register of Systematic Reviews (CRD42023455362). RESULTS We identified 19 sRCTs reporting a significant mortality reduction in adult critically ill patients. For 16 sRCTs, we identified at least one subsequent mRCT (24 trials in total), while the interventions from three sRCTs have not yet been addressed in a subsequent mRCT. Only one out of 16 sRCTs (6%) was followed by a mRCT replicating a significant mortality reduction; 14 (88%) were followed by mRCTs with no mortality difference. The positive finding of one sRCT (6%) on intensive glycemic control was contradicted by a subsequent mRCT showing a significant mortality increase. Of the 14 sRCTs referenced at least once in international guidelines, six (43%) have since been either removed or suggested against in the most recent versions of relevant guidelines. CONCLUSION Mortality reduction shown by sRCTs is typically not replicated by mRCTs. The findings of sRCTs should be considered hypothesis-generating and should not contribute to guidelines.
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Affiliation(s)
- Yuki Kotani
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy
- School of Medicine, Vita-Salute San Raffaele University, Via Olgettina 58, 20132, Milan, Italy
- Department of Intensive Care Medicine, Kameda Medical Center, 929 Higashi-cho, Kamogawa, Chiba, 296-8602, Japan
| | - Stefano Turi
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy
| | - Alessandro Ortalda
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy
| | - Martina Baiardo Redaelli
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy
| | - Cristiano Marchetti
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy
| | - Giovanni Landoni
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.
- School of Medicine, Vita-Salute San Raffaele University, Via Olgettina 58, 20132, Milan, Italy.
| | - Rinaldo Bellomo
- Department of Critical Care, The University of Melbourne, Melbourne, Australia
- Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia
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Zhang Y, Li H, Wang W, Shan L, Hao D. Assistive diagnostic indicators for infections related to lumbar posterior interbody fusion internal fixation: platelet count and mean platelet volume. J Orthop Surg Res 2023; 18:883. [PMID: 37986002 PMCID: PMC10658883 DOI: 10.1186/s13018-023-04358-4] [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: 08/09/2023] [Accepted: 11/08/2023] [Indexed: 11/22/2023] Open
Abstract
BACKGROUND The most severe complication after posterior single-segment lumbar interbody fusion and internal fixation (PIFIF) surgery for degenerative lumbar diseases is deep surgical site infection (DSSI). Preoperatively diagnosing such complications proves to be challenging. Platelets, as acute-phase reactants, undergo changes in response to infections and inflammation. This study aims to assess whether platelet indices can further aid in the diagnosis of DSSI. METHODS A single-center retrospective study was conducted from January 2016 to February 2021 at Xi'an Jiaotong University-Affiliated Honghui Hospital, involving 83 patients who underwent revision surgery after PIFIF due to lumbar degenerative diseases. Among them, 24 patients were diagnosed with DSSI based on combined bacterial culture and imaging data. Preoperative complete serological indicators including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and platelet count and mean platelet volume ratio (P/M ratio) were analyzed using receiver operating characteristic (ROC) curve analysis to determine cutoff values, sensitivity, and specificity. This was done to further assess the ability of these serological indicators to identify the occurrence of DSSI after PIFIF. RESULTS There were no significant differences in baseline demographic characteristics between the two patient groups (P > 0.05). The P/M ratio was 13.54 ± 5.05 in the aseptic revision group, while it was 19.21 ± 6.30 in the DSSI revision patients, showing a significant difference (P < 0.001). ROC curve analysis revealed that the optimal cutoff value for the P/M ratio was 17.50, with a sensitivity of 58.3% and a specificity of 78.6%. The areas under the curve (AUC) for ESR, CRP, and P/M ratio were 0.797, 0.845, and 0.756, respectively. The negative predictive value (NPV) was 87.04%, 89.47%, and 82.45%, respectively; the positive predictive value (PPV) was 58.62%, 69.23%, and 53.84%, respectively, for ESR, CRP, and P/M ratio, respectively. When P/M ratio is used in combination with ESR and CRP, the AUC is 0.887, with a sensitivity of 95.4%, specificity of 67.8%, NPV of 97.56%, PPV of 54.76%. The diagnostic performance of the model for evaluating DSSI is significantly improved compared to using ESR and CRP alone (P < 0.05). CONCLUSION Platelets and their related serum biomarkers are closely associated with DSSI. The P/M ratio can serve as a reliable test for screening DSSI and is worth considering for inclusion in the assessment of patients at risk of developing DSSI after potential PIFIF surgery.
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Affiliation(s)
- Yadong Zhang
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710054, Shaanxi, China
- Graduate School, Xi'an Medical University, Xi'an, 710068, Shaanxi, China
- Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, 710054, Shaanxi, China
| | - Houkun Li
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710054, Shaanxi, China
- Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, 710054, Shaanxi, China
| | - Wentao Wang
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710054, Shaanxi, China
| | - Lequn Shan
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710054, Shaanxi, China
| | - Dingjun Hao
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710054, Shaanxi, China.
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Xu H, Sheng S, Luo W, Xu X, Zhang Z. Acute respiratory distress syndrome heterogeneity and the septic ARDS subgroup. Front Immunol 2023; 14:1277161. [PMID: 38035100 PMCID: PMC10682474 DOI: 10.3389/fimmu.2023.1277161] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Accepted: 10/30/2023] [Indexed: 12/02/2023] Open
Abstract
Acute respiratory distress syndrome (ARDS) is an acute diffuse inflammatory lung injury characterized by the damage of alveolar epithelial cells and pulmonary capillary endothelial cells. It is mainly manifested by non-cardiogenic pulmonary edema, resulting from intrapulmonary and extrapulmonary risk factors. ARDS is often accompanied by immune system disturbance, both locally in the lungs and systemically. As a common heterogeneous disease in critical care medicine, researchers are often faced with the failure of clinical trials. Latent class analysis had been used to compensate for poor outcomes and found that targeted treatment after subgrouping contribute to ARDS therapy. The subphenotype of ARDS caused by sepsis has garnered attention due to its refractory nature and detrimental consequences. Sepsis stands as the most predominant extrapulmonary cause of ARDS, accounting for approximately 32% of ARDS cases. Studies indicate that sepsis-induced ARDS tends to be more severe than ARDS caused by other factors, leading to poorer prognosis and higher mortality rate. This comprehensive review delves into the immunological mechanisms of sepsis-ARDS, the heterogeneity of ARDS and existing research on targeted treatments, aiming to providing mechanism understanding and exploring ideas for accurate treatment of ARDS or sepsis-ARDS.
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Affiliation(s)
- Huikang Xu
- Department of Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Shiying Sheng
- Department of Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Weiwei Luo
- Department of Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Xiaofang Xu
- Department of Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Zhaocai Zhang
- Department of Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Key Laboratory of the Diagnosis and Treatment for Severe Trauma and Burn of Zhejiang Province, Hangzhou, China
- Zhejiang Province Clinical Research Center for Emergency and Critical Care Medicine, Hangzhou, China
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Steppan J, Wang H, Nandakumar K, Poe A, Pak L, Brady T, Gadkari M, Berkowitz DE, Shimoda LA, Santhanam L. LOXL2 inhibition ameliorates pulmonary artery remodeling in pulmonary hypertension. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.10.24.563874. [PMID: 37961202 PMCID: PMC10634806 DOI: 10.1101/2023.10.24.563874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2023]
Abstract
Background Conduit pulmonary arterial stiffening and the resultant increase in pulmonary vascular impedance has emerged as an important underlying driver of pulmonary arterial hypertension (PAH). Given that matrix deposition is central to vascular remodeling, we evaluated the role of the collagen crosslinking enzyme lysyl oxidase like 2 (LOXL2) in this study. Methods and Results Human pulmonary artery smooth muscle cells (PASMCs) subjected to hypoxia showed increased LOXL2 secretion. LOXL2 activity and expression were markedly higher in primary PASMCs isolated from pulmonary arteries of the rat Sugen 5416 + hypoxia (SuHx) model of severe PH. Similarly, LOXL2 protein and mRNA levels were increased in pulmonary arteries (PA) and lungs of rats with PH (SuHx and monocrotaline (MCT) models). Pulmonary arteries (PAs) isolated from rats with PH exhibited hypercontractility to phenylephrine and attenuated vasorelaxation elicited by acetylcholine, indicating severe endothelial dysfunction. Tensile testing revealed a a significant increase in PA stiffness in PH. Treatment with PAT-1251, a novel small-molecule LOXL2 inhibitor, improved active and passive properties of the PA ex vivo. There was an improvement in right heart function as measured by right ventricular pressure volume loops in-vivo with PAT-1251. Importantly PAT-1251 treatment ameliorated PH, resulting in improved pulmonary artery pressures, right ventricular remodeling, and survival. Conclusion Hypoxia induced LOXL2 activation is a causal mechanism in pulmonary artery stiffening in PH, as well as pulmonary artery mechanical and functional decline. LOXL2 inhibition with PAT-1251 is a promising approach to improve pulmonary artery pressures, right ventricular elastance, cardiac relaxation, and survival in PAH. New & Noteworthy Pulmonary arterial stiffening contributes to the progression of PAH and the deterioration of right heart function. This study shows that LOXL2 is upregulated in rat models of PH. LOXL2 inhibition halts pulmonary vascular remodeling and improves PA contractility, endothelial function and improves PA pressure, resulting in prolonged survival. Thus, LOXL2 is an important mediator of PA remodeling and stiffening in PH and a promising target to improve PA pressures and survival in PH.
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Abu-Khudir R, Hafsa N, Badr BE. Identifying Effective Biomarkers for Accurate Pancreatic Cancer Prognosis Using Statistical Machine Learning. Diagnostics (Basel) 2023; 13:3091. [PMID: 37835833 PMCID: PMC10572229 DOI: 10.3390/diagnostics13193091] [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: 06/01/2023] [Revised: 09/08/2023] [Accepted: 09/26/2023] [Indexed: 10/15/2023] Open
Abstract
Pancreatic cancer (PC) has one of the lowest survival rates among all major types of cancer. Consequently, it is one of the leading causes of mortality worldwide. Serum biomarkers historically correlate well with the early prognosis of post-surgical complications of PC. However, attempts to identify an effective biomarker panel for the successful prognosis of PC were almost non-existent in the current literature. The current study investigated the roles of various serum biomarkers including carbohydrate antigen 19-9 (CA19-9), chemokine (C-X-C motif) ligand 8 (CXCL-8), procalcitonin (PCT), and other relevant clinical data for identifying PC progression, classified into sepsis, recurrence, and other post-surgical complications, among PC patients. The most relevant biochemical and clinical markers for PC prognosis were identified using a random-forest-powered feature elimination method. Using this informative biomarker panel, the selected machine-learning (ML) classification models demonstrated highly accurate results for classifying PC patients into three complication groups on independent test data. The superiority of the combined biomarker panel (Max AUC-ROC = 100%) was further established over using CA19-9 features exclusively (Max AUC-ROC = 75%) for the task of classifying PC progression. This novel study demonstrates the effectiveness of the combined biomarker panel in successfully diagnosing PC progression and other relevant complications among Egyptian PC survivors.
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Affiliation(s)
- Rasha Abu-Khudir
- Chemistry Department, College of Science, King Faisal University, P.O. Box 380, Hofuf 31982, Al-Ahsa, Saudi Arabia
- Chemistry Department, Biochemistry Branch, Faculty of Science, Tanta University, Tanta 31527, Egypt
| | - Noor Hafsa
- Computer Science Department, College of Computer Science and Information Technology, King Faisal University, P.O. Box 400, Hofuf 31982, Al-Ahsa, Saudi Arabia;
| | - Badr E. Badr
- Egyptian Ministry of Labor, Training and Research Department, Tanta 31512, Egypt;
- Botany Department, Microbiology Unit, Faculty of Science, Tanta University, Tanta 31527, Egypt
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Xu H, Lu JP. Spontaneous rupture of the spleen at full term during pregnancy: a case report. J Int Med Res 2023; 51:3000605231196818. [PMID: 37669438 PMCID: PMC10481704 DOI: 10.1177/03000605231196818] [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: 04/02/2023] [Accepted: 06/19/2023] [Indexed: 09/07/2023] Open
Abstract
Spontaneous rupture of the spleen during pregnancy is a rare, fatal disease. This condition is easily misdiagnosed as uterine rupture, placental abruption, or other obstetric diseases; and if a timely diagnosis is not made and effective treatment instituted, serious sequelae rapidly develop, including hemorrhagic shock and maternal and fetal death. Here, we report a case of spontaneous splenic rupture in a woman in her third trimester of pregnancy. Furthermore, through a literature review, we discuss the possible presentations, symptoms, and causes of splenic rupture during pregnancy, in the hope of facilitating the early diagnosis and treatment of this condition.
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Affiliation(s)
- Heng Xu
- Department of Obstetrics, Jinhua People’s Hospital, Jinhua, Zhejiang, China
| | - Jia-Ping Lu
- Department of Obstetrics, Jinhua People’s Hospital, Jinhua, Zhejiang, China
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Raheja R, Reddy N, Patel T, Kilambi S, Mathew AA, Majeed A. Classification of Chemotherapy-Induced Febrile Neutropenic Episodes Into One of the Three Febrile Neutropenic Syndromes. Cureus 2023; 15:e42843. [PMID: 37664262 PMCID: PMC10472482 DOI: 10.7759/cureus.42843] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/31/2023] [Indexed: 09/05/2023] Open
Abstract
Introduction Febrile neutropenia is a commonly encountered medical emergency in patients undergoing cancer treatment and can delay and modify the course of treatment and even lead to dire outcomes, including death. The cause of fever in a post-chemotherapy-induced neutropenic patient can be confusing to treating physicians. A review of the literature demonstrated that blood culture results could determine the cause of febrile neutropenia in only approximately 10% to 25% of patients. The objective of our study was to measure the incidence of positive blood cultures, urine cultures, and other body fluid cultures resulting in chemotherapy-induced neutropenia and further classify fever episodes into three neutropenic fever syndromes, such as microbiologically documented, clinically suspected, or unknown causes of fever, respectively. Methods We conducted a prospective observational study on 399 chemotherapy-induced neutropenic fever episodes with the aim of classifying them into one of the three neutropenic syndromes. We tried to document the cause of the fever in these patients. We also noted the type of cancer treatment regimen they were on and correlated their clinical profile with their body fluid cultures, including blood cultures, urine cultures, and other body fluid cultures. We then categorized each fever episode into one of three neutropenic syndromes. Results We studied 399 febrile neutropenic episodes. We were able to microbiologically document the cause of fever in 39% of the cases, and we obtained growth in 51 out of 399 blood cultures (13%), which was comparable to the available literature, and urine culture showed growth in 62 out of 399 cultures (16%), while other body cultures such as pus culture, bile culture, and bronchioalveolar lavage cultures collectively showed growth in 42 out of 399 episodes (10%). The most common bacteria isolated in both blood and urine cultures were Escherichia coli. Cumulatively, including blood, urine, and body fluid cultures, we were able to classify 39% (155 out of 399 cases) of febrile neutropenic episodes as microbiologically documented. The cause of fever was clinically suspected by means of careful history taking and an extensive physical examination in 31% (125 out of 399) without growth evidence in blood cultures, urine cultures, or any other body fluid culture. The cause of fever remained unknown in 119 cases (30%) of patients and was classified under the unknown cause of fever. Conclusions We conclude by stating that the study of fever in a neutropenic patient should include a thorough history and clinical evaluation of blood, urine, and other body fluid cultures instead of solely relying on blood culture results. We recommend further classifying patients into one of the three neutropenic fever syndromes, such as those that are microbiologically documented, clinically suspected, or unknown. Our blood cultures were able to give us a 13% positivity rate, whereas microbiologically, we were able to isolate an organism likely causing fever in 39% of patients. The cause of fever was suspected clinically in 31% of patients, but we were unsuccessful in microbiologically documenting any culture growth in blood, urine, or any other body fluid culture. The cause of fever remained a mystery and unknown to us without any microbiological or clinical cues in 119 cases (30%) of febrile neutropenic episodes.
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Affiliation(s)
- Ronak Raheja
- Department of Internal Medicine, Kempegowda Institute of Medical Sciences, Bengaluru, IND
| | - Neelesh Reddy
- Department of Medical Oncology, Columbia Asia Referral Hospital Yeshwanthpur, Bangalore, IND
| | - Twinkle Patel
- Department of Internal Medicine, Shri Sathya Sai Medical College and Research Institute, Surat, IND
| | - Srikar Kilambi
- College of Medicine, Sri Ramachandra Institute of Higher Education and Research, Chennai, IND
| | - Ashik A Mathew
- Department of Pharmacology and Therapeutics, Manipal Hospitals, Bangalore, IND
| | - Abdul Majeed
- Department of Internal Medicine, Columbia Asia Referral Hospital Yeshwanthpur, Bangalore, IND
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Lin ZW, Liu YY, Chen XH, Zheng YR, Cao H, Chen Q. Clinical effect of early enteral nutrition support on critically ill neonates with extracorporeal membrane oxygenation. BMC Pediatr 2023; 23:359. [PMID: 37442946 PMCID: PMC10339525 DOI: 10.1186/s12887-023-04171-2] [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: 03/10/2023] [Accepted: 07/02/2023] [Indexed: 07/15/2023] Open
Abstract
OBJECTIVE To investigate the feasibility and clinical outcomes of early enteral nutrition (EN) in critically ill neonates supported by extracorporeal membrane oxygenation (ECMO). METHODS We retrospectively analyzed the clinical data of 16 critically ill neonates who received ECMO support for respiratory and circulatory failure from July 2021 to December 2022 at our center. The patients were divided into two groups: the early EN group (< 24 h) and the late EN group (> 24 h). The related clinical and nutrition-related indicators between the groups were compared. RESULTS There was a significant difference in the time from ECMO treatment to the start of EN between the early EN group (9 patients, 56.2%) and the late EN group (7 patients, 43.8%) (P < 0.05). However, there were no significant differences in ECMO duration, hospitalization time, vasoactive-inotropic score (VIS), intestinal oxygen saturation, or routine stool occult blood (OB) test between the two groups (all P > 0.05). The incidence of complications such as intestinal obstruction, abdominal distension, diarrhea, and necrotizing enterocolitis (NEC) was slightly lower in the early EN group, but the differences were not statistically significant (all P > 0.05). The early EN group had a shorter time [3.6 (3.5, 5) vs. 7.5 (5.9, 8.5) d] to reach full gastrointestinal nutrition compared to the late EN group (P < 0.05). CONCLUSION Providing early nutritional support through enteral feeding to critically ill neonates receiving ECMO treatment is both safe and practical, but close monitoring of clinical and nutritional indicators is essential.
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Affiliation(s)
- Ze-Wei Lin
- Department of Cardiac Surgery, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Ying-Ying Liu
- Department of Cardiac Surgery, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Xiu-Hua Chen
- Department of Cardiac Surgery, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Yi-Rong Zheng
- Department of Cardiac Surgery, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Hua Cao
- Department of Cardiac Surgery, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Qiang Chen
- Department of Cardiac Surgery, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China.
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Xie C, Wang P, Wu H, Hu X, Nie T, Li X, Pang P, Li G, Lu Y, Yang X, Wang X, Li C, You X. Protective effect of the novel cyclic peptide ASK0912 on mice with sepsis induced by Acinetobacter baumannii. Biomed Pharmacother 2023; 164:114965. [PMID: 37295247 DOI: 10.1016/j.biopha.2023.114965] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 05/13/2023] [Accepted: 05/22/2023] [Indexed: 06/12/2023] Open
Abstract
BACKGROUND Sepsis has become a global health concern owing to its increasing incidence and high mortality rate. In the present study, we investigated a novel drug candidate ASK0912 on its protective effects in mice with Acinetobacter baumannii 20-1-induced sepsis, and studied the related mechanisms. MATERIAL AND METHODS To analyze the protective effect of ASK0912 on septic mice, survival rates, body temperature, organ and blood bacterial loads, white blood cell and platelet counts, organ damage, and cytokine levels were determined. RESULTS ASK0912 remarkably increased the survival rate of mice with sepsis induced by A. baumannii 20-1 at a low dose of 0.6 mg/kg. Rectal temperature measurements showed that ASK0912 treatment prevented the body temperature decrease of septic mice to some extent. Treatment with ASK0912 can notably reduce the organ and blood bacterial loads and alleviate platelet count reduction due to sepsis. ASK0912 attenuated organ damage, including reduced levels of total bile acids, urea, and creatinine, aggregation of inflammatory cells, and mitigation of structural changes in septic mice, as demonstrated by biochemical analysis and hematoxylin & eosin staining. Additionally, multiplex assay showed that abnormally increased cytokine levels (IL-1β, IL-3, IL-5, IL-6, IL-10, IL-13, MCP-1, RANTES, KC, MIP-1α, MIP-1β, and G-CSF) in septic mice decreased after ASK0912 treatment. CONCLUSIONS ASK0912 can not only improve the survival rate, hypothermia, lower the bacterial loads in the organs and blood, but also alleviate the pathophysiological manifestations such as intravascular coagulation abnormalities, organ damages, and immune system disorder of sepsis mice induced by A. baumannii 20-1.
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Affiliation(s)
- Chunyang Xie
- Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
| | - Penghe Wang
- Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
| | - Huige Wu
- Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
| | - Xinxin Hu
- Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
| | - Tongying Nie
- Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
| | - Xue Li
- Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
| | - Pengbo Pang
- Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
| | - Guoqing Li
- Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
| | - Yun Lu
- Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
| | - Xinyi Yang
- Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
| | - Xiukun Wang
- Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
| | - Congran Li
- Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
| | - Xuefu You
- Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
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Kirkpatrick AW, Coccolini F, Tolonen M, Minor S, Catena F, Gois E, Doig CJ, Hill MD, Ansaloni L, Chiarugi M, Tartaglia D, Ioannidis O, Sugrue M, Colak E, Hameed SM, Lampela H, Agnoletti V, McKee JL, Garraway N, Sartelli M, Ball CG, Parry NG, Voght K, Julien L, Kroeker J, Roberts DJ, Faris P, Tiruta C, Moore EE, Ammons LA, Anestiadou E, Bendinelli C, Bouliaris K, Carroll R, Ceresoli M, Favi F, Gurrado A, Rezende-Neto J, Isik A, Cremonini C, Strambi S, Koukoulis G, Testini M, Trpcic S, Pasculli A, Picariello E, Abu-Zidan F, Adeyeye A, Augustin G, Alconchel F, Altinel Y, Hernandez Amin LA, Aranda-Narváez JM, Baraket O, Biffl WL, Baiocchi GL, Bonavina L, Brisinda G, Cardinali L, Celotti A, Chaouch M, Chiarello M, Costa G, de'Angelis N, De Manzini N, Delibegovic S, Di Saverio S, De Simone B, Dubuisson V, Fransvea P, Garulli G, Giordano A, Gomes C, Hayati F, Huang J, Ibrahim AF, Huei TJ, Jailani RF, Khan M, Luna AP, Malbrain MLNG, Marwah S, McBeth P, Mihailescu A, Morello A, Mulita F, Murzi V, Mohammad AT, Parmar S, Pak A, Wong MPK, Pantalone D, Podda M, Puccioni C, Rasa K, Ren J, Roscio F, Gonzalez-Sanchez A, Sganga G, Scheiterle M, et alKirkpatrick AW, Coccolini F, Tolonen M, Minor S, Catena F, Gois E, Doig CJ, Hill MD, Ansaloni L, Chiarugi M, Tartaglia D, Ioannidis O, Sugrue M, Colak E, Hameed SM, Lampela H, Agnoletti V, McKee JL, Garraway N, Sartelli M, Ball CG, Parry NG, Voght K, Julien L, Kroeker J, Roberts DJ, Faris P, Tiruta C, Moore EE, Ammons LA, Anestiadou E, Bendinelli C, Bouliaris K, Carroll R, Ceresoli M, Favi F, Gurrado A, Rezende-Neto J, Isik A, Cremonini C, Strambi S, Koukoulis G, Testini M, Trpcic S, Pasculli A, Picariello E, Abu-Zidan F, Adeyeye A, Augustin G, Alconchel F, Altinel Y, Hernandez Amin LA, Aranda-Narváez JM, Baraket O, Biffl WL, Baiocchi GL, Bonavina L, Brisinda G, Cardinali L, Celotti A, Chaouch M, Chiarello M, Costa G, de'Angelis N, De Manzini N, Delibegovic S, Di Saverio S, De Simone B, Dubuisson V, Fransvea P, Garulli G, Giordano A, Gomes C, Hayati F, Huang J, Ibrahim AF, Huei TJ, Jailani RF, Khan M, Luna AP, Malbrain MLNG, Marwah S, McBeth P, Mihailescu A, Morello A, Mulita F, Murzi V, Mohammad AT, Parmar S, Pak A, Wong MPK, Pantalone D, Podda M, Puccioni C, Rasa K, Ren J, Roscio F, Gonzalez-Sanchez A, Sganga G, Scheiterle M, Slavchev M, Smirnov D, Tosi L, Trivedi A, Vega JAG, Waledziak M, Xenaki S, Winter D, Wu X, Zakaria AD, Zakaria Z. The unrestricted global effort to complete the COOL trial. World J Emerg Surg 2023; 18:33. [PMID: 37170123 DOI: 10.1186/s13017-023-00500-z.pmid:] [Show More Authors] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 04/13/2023] [Indexed: 07/14/2024] Open
Abstract
BACKGROUND Severe complicated intra-abdominal sepsis (SCIAS) has an increasing incidence with mortality rates over 80% in some settings. Mortality typically results from disruption of the gastrointestinal tract, progressive and self-perpetuating bio-mediator generation, systemic inflammation, and multiple organ failure. A further therapeutic option may be open abdomen (OA) management with negative peritoneal pressure therapy (NPPT) to remove inflammatory ascites and attenuate the systemic damage from SCIAS, although there are definite risks of leaving the abdomen open whenever it might possibly be closed. This potential therapeutic paradigm is the rationale being assessed in the Closed Or Open after Laparotomy (COOL trial) ( https://clinicaltrials.gov/ct2/show/NCT03163095 ). Initially, the COOL trial received Industry sponsorship; however, this funding mandated the use of a specific trademarked and expensive NPPT device in half of the patients allocated to the intervention (open) arm. In August 2022, the 3 M/Acelity Corporation without consultation but within the terms of the contract canceled the financial support of the trial. Although creating financial difficulty, there is now no restriction on specific NPPT devices and removing a cost-prohibitive intervention creates an opportunity to expand the COOL trial to a truly global basis. This document describes the evolution of the COOL trial, with a focus on future opportunities for global growth of the study. METHODS The COOL trial is the largest prospective randomized controlled trial examining the random allocation of SCIAS patients intra-operatively to either formal closure of the fascia or the use of the OA with an application of an NPPT dressing. Patients are eligible if they have free uncontained intraperitoneal contamination and physiologic derangements exemplified by septic shock OR severely adverse predicted clinical outcomes. The primary outcome is intended to definitively inform global practice by conclusively evaluating 90-day survival. Initial recruitment has been lower than hoped but satisfactory, and the COOL steering committee and trial investigators intend with increased global support to continue enrollment until recruitment ensures a definitive answer. DISCUSSION OA is mandated in many cases of SCIAS such as the risk of abdominal compartment syndrome associated with closure, or a planned second look as for example part of "damage control"; however, improved source control (locally and systemically) is the most uncertain indication for an OA. The COOL trial seeks to expand potential sites and proceed with the evaluation of NPPT agnostic to device, to properly examine the hypothesis that this treatment attenuates systemic damage and improves survival. This approach will not affect internal validity and should improve the external validity of any observed results of the intervention. TRIAL REGISTRATION National Institutes of Health ( https://clinicaltrials.gov/ct2/show/NCT03163095 ).
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Affiliation(s)
- Andrew W Kirkpatrick
- Departments of Surgery and Critical Care Medicine, University of Calgary, Foothills Medical Centre, Calgary, AB, EG23T2N 2T9, Canada.
| | - Federico Coccolini
- General, Emergency and Trauma Surgery Department, Pisa University Hospital, Pisa, Italy
| | - Matti Tolonen
- Abdominal Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Samuel Minor
- Departments of Critical Care Medicine and Surgery, Dalhousie University, Halifax, NS, Canada
| | - Fausto Catena
- Department of Surgery, Bufalini Hospital, Cesena, Italy
| | - Emanuel Gois
- Department of Surgery, Londrina State University, and National COOL Coordinator for Brazil, Londrina, Brazil
| | - Christopher J Doig
- Departments of Critical Care Medicine and Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Michael D Hill
- Department of Clinical Neuroscience and Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary and Foothills Medical Centre, Calgary, AB, Canada
| | - Luca Ansaloni
- General Surgery I, San Matteo Hospital Pavia, University of Pavia, Pavia, Italy
| | - Massimo Chiarugi
- Emergency Surgery and Trauma Center, University of Pisa, Pisa, Italy
| | - Dario Tartaglia
- Emergency Surgery and Trauma Center, University of Pisa, Pisa, Italy
| | - Orestis Ioannidis
- 4th Department of Surgery, Medical School, Aristotle University of Thessaloniki, General Hospital "George Papanikolaou", Thessaloniki, Greece
| | | | - Elif Colak
- University of Samsun, Samsun Training and Research Hospital, Samsun, Turkey
| | - S Morad Hameed
- Department of Surgery, University of British Columbia, Vancouver, BC, Canada
| | - Hanna Lampela
- Department of Gastroenterological Surgery, Helsinki University Hospital and University of Helsinki, Espoo, Finland
| | | | - Jessica L McKee
- Global Project Manager, COOL Trial and the TeleMentored Ultrasound Supported Medical Interventions Research Group, Calgary, AB, Canada
| | - Naisan Garraway
- Departments of Surgery and Critical Care Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Massimo Sartelli
- Department of Surgery, Macerata Hospital, Global Alliance for Infections in Surgery, Macerata, Italy
| | - Chad G Ball
- Trauma and Acute Care Surgery, Foothills Medical Center, Calgary, AB, Canada
| | - Neil G Parry
- Departments of Surgery and Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
| | - Kelly Voght
- Departments of Surgery and Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
| | - Lisa Julien
- Department of Surgery, NSHA-Queen Elizabeth II Health Sciences Center, Dalhousie University, Halifax, NS, Canada
| | - Jenna Kroeker
- Departments of Surgery and Critical Care Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Derek J Roberts
- Division of Vascular and Endovascular Surgery, Department of Surgery and School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | | | | | - Ernest E Moore
- Ernest E. Moore Shock Trauma Center, University of Colorado, Denver, CO, USA
| | | | - Elissavet Anestiadou
- 4th Department of Surgery, Medical School, Aristotle University of Thessaloniki, General Hospital "George Papanikolaou", Thessaloniki, Greece
| | | | - Konstantinos Bouliaris
- General Surgery Department of Koutlimbaneio, Triantafylleio General Hospital of Larissa, Larissa, Thessaly, Greece
| | | | - Marco Ceresoli
- General and Emergency Surgery, School of Medicine and Surgery, Milano-Bicocca University, Monza, Italy
| | - Francesco Favi
- Chirurgia Generale E d'Urgenza, Ospedale M. Bufalini - Cesena, AUSL Della Romagna, Cesena, Italy
| | - Angela Gurrado
- Department of Precision and Regenerative Medicine and Ionian Area, Unit of Academic General Surgery "V. Bonomo", University of Bari "A. Moro", Bari, Italy
| | - Joao Rezende-Neto
- Trauma and Acute Care Surgery, General Surgery, St. Michael's Hospital, Toronto, ON, Canada
| | - Arda Isik
- General Surgery Department, Istanbul Medeniyet University School of Medicine Istanbul, Istanbul, Turkey
| | - Camilla Cremonini
- Emergency Surgery and Trauma Center, University of Pisa, Pisa, Italy
| | - Silivia Strambi
- Emergency Surgery and Trauma Center, University of Pisa, Pisa, Italy
| | - Georgios Koukoulis
- General Surgery Department of Koutlimbaneio, Triantafylleio General Hospital of Larissa, Larissa, Thessaly, Greece
| | - Mario Testini
- Department of Precision and Regenerative Medicine and Ionian Area, Unit of Academic General Surgery "V. Bonomo", University of Bari "A. Moro", Bari, Italy
| | - Sandy Trpcic
- Trauma and Acute Care Surgery, General Surgery, St. Michael's Hospital, Toronto, ON, Canada
| | - Alessandro Pasculli
- Department of Precision and Regenerative Medicine and Ionian Area, Unit of Academic General Surgery "V. Bonomo", University of Bari "A. Moro", Bari, Italy
| | - Erika Picariello
- General Surgery Unit, Ospedale M. Buffalini Di Cesena, Cesena, Italy
| | - Fikri Abu-Zidan
- College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates
| | - Ademola Adeyeye
- Division of Surgical Oncology, Afe Babalola University Multisystem Hospital, Ado-Ekiti, Nigeria
| | - Goran Augustin
- University Hospital Centre Zagreb, School of Medicine University of Zagreb, Zagreb, Croatia
| | - Felipe Alconchel
- Virgen de la Arrixaca University Hospital IMIB-Arrixaca, Ctra. Madrid-Cartagena, S/N, Murcia, Spain
| | - Yuksel Altinel
- Bagcilar Research and Training Hospital, Istanbul, Turkey
| | - Luz Adriana Hernandez Amin
- Nurse Master of Nursing, Professor and Coordinator of the teaching-service relationship, Faculty of Health Sciences, University of Sucre, Sincelejo, Colombia
| | - José Manuel Aranda-Narváez
- Trauma and Emergency Surgery Unit. General, Digestive and Transplantation Surgery Department, University Regional Hospital of Málaga, Malaga, Spain
| | | | | | - Gian Luca Baiocchi
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Luigi Bonavina
- Department of Surgery, University of Milan Medical School, Milan, Italy
| | - Giuseppe Brisinda
- Department of Surgery, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy
| | - Luca Cardinali
- Department of Surgery, General Hospital Madonna del Soccorso, San Benedetto del Tronto, Italy
| | - Andrea Celotti
- General Surgery Unit, UO Chirurgia Generale - Ospedale Maggiore Di Cremona, Cremona, Italy
| | - Mohamed Chaouch
- Department of Visceral and Digestive Surgery, Monastir University, Monastir, Tunisia
| | - Maria Chiarello
- Department of Surgery, Azienda Sanitaria Provinciale Di Cosenza, Cosenza, Italy
| | - Gianluca Costa
- Fondazione Policlinico Campus Bio-Medico, University Campus Bio-Medico of Rome, Rome, Italy
| | - Nicola de'Angelis
- Colorectal and Digestive Surgery Unit-DIGEST Department, Beaujon University Hospital AP-HP, University Paris Cité, Clichy, France
| | - Nicolo De Manzini
- Department of General Surgery, Cattinara University Hospital, Trieste, Italy
| | - Samir Delibegovic
- Department of Proctology, Clinic for Surgery, University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina
| | - Salomone Di Saverio
- Department of General Surgery, University of Insubria, University Hospital of Varese, ASST Sette Laghi, Regione Lombardia, Italy
| | - Belinda De Simone
- Unit of Digestive and Metabolic Minimally Invasive Surgery, Clinique Saint Louis, Poissy, Poissy, Ile de France, France
- Unit of Emergency and General Surgery, Guastalla Hospital, AUSL Reggio Emilia, Guastalla, Italy
| | - Vincent Dubuisson
- Chirurgie Digestive, Service de Chirurgie Vasculaire Et, Générale University Hospital of Bordeaux FR, Bordeaux, France
| | | | | | - Alessio Giordano
- Emergency and General Consultant Surgeon, Nuovo Ospedale "S. Stefano", Azienda ASL Toscana Centro, Prato, Italy
| | - Carlos Gomes
- Surgery Unit, Hospital Universitário Terezinha de Jesus, SUPREMA, Juiz de Fora, Brazil
| | - Firdaus Hayati
- Department of Surgery, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu, Sabah, Malaysia
| | - Jinjian Huang
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | | | | | | | - Mansoor Khan
- General Surgery, University Hospitals, Sussex, UK
| | | | - Manu L N G Malbrain
- First Department of Anaesthesiology and Intensive Therapy, Medical University of Lublin, Lublin, Poland
- International Fluid Academy, Lovenjoel, Belgium
| | - Sanjay Marwah
- Postgraduate Institute of Medical Sciences, Rohtak, Haryana, India
| | | | | | - Alessia Morello
- Department of General Surgery, Madonna del Soccorso Hospital - San Benedetto del Tronto, Italy, Italy
| | - Francesk Mulita
- Department of Surgery, General University Hospital of Patras, Rio, Greece
| | - Valentina Murzi
- Department of Surgical Science, Cagliari State University, Cagliari, Italy
| | | | | | - Ajay Pak
- Department of General Surgery, King George's Medical University, Lucknow, UP, India
| | - Michael Pak-Kai Wong
- School of Medical Sciences & Hospital, Universiti Sains Malaysia, Kelantan, Malaysia
| | | | - Mauro Podda
- Department of Emergency Surgery, Cagliari University Hospital, Cagliari, Italy
| | - Caterina Puccioni
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of Sacred Heart, Rome, Italy
| | - Kemal Rasa
- Department of General Surgery, Hüseyin Kemal Raşa, Anadolu Medical Center, Kocaeli, Turkey
| | - Jianan Ren
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Francesco Roscio
- Division of General and Minimally Invasive Surgery, ASST Valle Olona, Busto Arsizio, Italy
| | - Antonio Gonzalez-Sanchez
- Trauma and Emergency Surgery Unit. General, Digestive and Transplantation Surgery Department, University Regional Hospital of Málaga, Malaga, Spain
| | - Gabriele Sganga
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of Sacred Heart, Rome, Italy
| | - Maximilian Scheiterle
- Emergency Surgery Unit and Trauma Team, Careggi University Hospital, Florence, Italy
| | | | - Dmitry Smirnov
- Department of Surgery, South Ural State Medical University, Chelyabinsk City, Russia
| | - Lorenzo Tosi
- Department of General Surgery, University of Bologna, Bologna, Italy
| | | | | | | | - Sofia Xenaki
- Department of General Surgery, University Hospital of Heraklion, Crete, Greece
| | | | - Xiuwen Wu
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Andee Dzulkarnean Zakaria
- Department of Surgery, School of Medical Sciences and Hospital USM, Universiti Sains Malaysia, Georgetown, Malaysia
| | - Zaidi Zakaria
- Department of Surgery, School of Medical Sciences and Hospital USM, Universiti Sains Malaysia, Georgetown, Malaysia
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Kirkpatrick AW, Coccolini F, Tolonen M, Minor S, Catena F, Gois E, Doig CJ, Hill MD, Ansaloni L, Chiarugi M, Tartaglia D, Ioannidis O, Sugrue M, Colak E, Hameed SM, Lampela H, Agnoletti V, McKee JL, Garraway N, Sartelli M, Ball CG, Parry NG, Voght K, Julien L, Kroeker J, Roberts DJ, Faris P, Tiruta C, Moore EE, Ammons LA, Anestiadou E, Bendinelli C, Bouliaris K, Carroll R, Ceresoli M, Favi F, Gurrado A, Rezende-Neto J, Isik A, Cremonini C, Strambi S, Koukoulis G, Testini M, Trpcic S, Pasculli A, Picariello E, Abu-Zidan F, Adeyeye A, Augustin G, Alconchel F, Altinel Y, Hernandez Amin LA, Aranda-Narváez JM, Baraket O, Biffl WL, Baiocchi GL, Bonavina L, Brisinda G, Cardinali L, Celotti A, Chaouch M, Chiarello M, Costa G, de’Angelis N, De Manzini N, Delibegovic S, Di Saverio S, De Simone B, Dubuisson V, Fransvea P, Garulli G, Giordano A, Gomes C, Hayati F, Huang J, Ibrahim AF, Huei TJ, Jailani RF, Khan M, Luna AP, Malbrain MLNG, Marwah S, McBeth P, Mihailescu A, Morello A, Mulita F, Murzi V, Mohammad AT, Parmar S, Pak A, Wong MPK, Pantalone D, Podda M, Puccioni C, Rasa K, Ren J, Roscio F, Gonzalez-Sanchez A, Sganga G, Scheiterle M, et alKirkpatrick AW, Coccolini F, Tolonen M, Minor S, Catena F, Gois E, Doig CJ, Hill MD, Ansaloni L, Chiarugi M, Tartaglia D, Ioannidis O, Sugrue M, Colak E, Hameed SM, Lampela H, Agnoletti V, McKee JL, Garraway N, Sartelli M, Ball CG, Parry NG, Voght K, Julien L, Kroeker J, Roberts DJ, Faris P, Tiruta C, Moore EE, Ammons LA, Anestiadou E, Bendinelli C, Bouliaris K, Carroll R, Ceresoli M, Favi F, Gurrado A, Rezende-Neto J, Isik A, Cremonini C, Strambi S, Koukoulis G, Testini M, Trpcic S, Pasculli A, Picariello E, Abu-Zidan F, Adeyeye A, Augustin G, Alconchel F, Altinel Y, Hernandez Amin LA, Aranda-Narváez JM, Baraket O, Biffl WL, Baiocchi GL, Bonavina L, Brisinda G, Cardinali L, Celotti A, Chaouch M, Chiarello M, Costa G, de’Angelis N, De Manzini N, Delibegovic S, Di Saverio S, De Simone B, Dubuisson V, Fransvea P, Garulli G, Giordano A, Gomes C, Hayati F, Huang J, Ibrahim AF, Huei TJ, Jailani RF, Khan M, Luna AP, Malbrain MLNG, Marwah S, McBeth P, Mihailescu A, Morello A, Mulita F, Murzi V, Mohammad AT, Parmar S, Pak A, Wong MPK, Pantalone D, Podda M, Puccioni C, Rasa K, Ren J, Roscio F, Gonzalez-Sanchez A, Sganga G, Scheiterle M, Slavchev M, Smirnov D, Tosi L, Trivedi A, Vega JAG, Waledziak M, Xenaki S, Winter D, Wu X, Zakaria AD, Zakaria Z. The unrestricted global effort to complete the COOL trial. World J Emerg Surg 2023; 18:33. [PMID: 37170123 PMCID: PMC10173926 DOI: 10.1186/s13017-023-00500-z] [Show More Authors] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 04/13/2023] [Indexed: 05/13/2023] Open
Abstract
BACKGROUND Severe complicated intra-abdominal sepsis (SCIAS) has an increasing incidence with mortality rates over 80% in some settings. Mortality typically results from disruption of the gastrointestinal tract, progressive and self-perpetuating bio-mediator generation, systemic inflammation, and multiple organ failure. A further therapeutic option may be open abdomen (OA) management with negative peritoneal pressure therapy (NPPT) to remove inflammatory ascites and attenuate the systemic damage from SCIAS, although there are definite risks of leaving the abdomen open whenever it might possibly be closed. This potential therapeutic paradigm is the rationale being assessed in the Closed Or Open after Laparotomy (COOL trial) ( https://clinicaltrials.gov/ct2/show/NCT03163095 ). Initially, the COOL trial received Industry sponsorship; however, this funding mandated the use of a specific trademarked and expensive NPPT device in half of the patients allocated to the intervention (open) arm. In August 2022, the 3 M/Acelity Corporation without consultation but within the terms of the contract canceled the financial support of the trial. Although creating financial difficulty, there is now no restriction on specific NPPT devices and removing a cost-prohibitive intervention creates an opportunity to expand the COOL trial to a truly global basis. This document describes the evolution of the COOL trial, with a focus on future opportunities for global growth of the study. METHODS The COOL trial is the largest prospective randomized controlled trial examining the random allocation of SCIAS patients intra-operatively to either formal closure of the fascia or the use of the OA with an application of an NPPT dressing. Patients are eligible if they have free uncontained intraperitoneal contamination and physiologic derangements exemplified by septic shock OR severely adverse predicted clinical outcomes. The primary outcome is intended to definitively inform global practice by conclusively evaluating 90-day survival. Initial recruitment has been lower than hoped but satisfactory, and the COOL steering committee and trial investigators intend with increased global support to continue enrollment until recruitment ensures a definitive answer. DISCUSSION OA is mandated in many cases of SCIAS such as the risk of abdominal compartment syndrome associated with closure, or a planned second look as for example part of "damage control"; however, improved source control (locally and systemically) is the most uncertain indication for an OA. The COOL trial seeks to expand potential sites and proceed with the evaluation of NPPT agnostic to device, to properly examine the hypothesis that this treatment attenuates systemic damage and improves survival. This approach will not affect internal validity and should improve the external validity of any observed results of the intervention. TRIAL REGISTRATION National Institutes of Health ( https://clinicaltrials.gov/ct2/show/NCT03163095 ).
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Affiliation(s)
- Andrew W. Kirkpatrick
- Departments of Surgery and Critical Care Medicine, University of Calgary, Foothills Medical Centre, Calgary, AB EG23T2N 2T9 Canada
| | - Federico Coccolini
- General, Emergency and Trauma Surgery Department, Pisa University Hospital, Pisa, Italy
| | - Matti Tolonen
- Abdominal Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Samuel Minor
- Departments of Critical Care Medicine and Surgery, Dalhousie University, Halifax, NS Canada
| | - Fausto Catena
- Department of Surgery, Bufalini Hospital, Cesena, Italy
| | - Emanuel Gois
- Department of Surgery, Londrina State University, and National COOL Coordinator for Brazil, Londrina, Brazil
| | - Christopher J. Doig
- Departments of Critical Care Medicine and Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB Canada
| | - Michael D. Hill
- Department of Clinical Neuroscience and Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary and Foothills Medical Centre, Calgary, AB Canada
| | - Luca Ansaloni
- General Surgery I, San Matteo Hospital Pavia, University of Pavia, Pavia, Italy
| | - Massimo Chiarugi
- Emergency Surgery and Trauma Center, University of Pisa, Pisa, Italy
| | - Dario Tartaglia
- Emergency Surgery and Trauma Center, University of Pisa, Pisa, Italy
| | - Orestis Ioannidis
- 4th Department of Surgery, Medical School, Aristotle University of Thessaloniki, General Hospital “George Papanikolaou”, Thessaloniki, Greece
| | | | - Elif Colak
- University of Samsun, Samsun Training and Research Hospital, Samsun, Turkey
| | - S. Morad Hameed
- Department of Surgery, University of British Columbia, Vancouver, BC Canada
| | - Hanna Lampela
- Department of Gastroenterological Surgery, Helsinki University Hospital and University of Helsinki, Espoo, Finland
| | | | - Jessica L. McKee
- Global Project Manager, COOL Trial and the TeleMentored Ultrasound Supported Medical Interventions Research Group, Calgary, AB Canada
| | - Naisan Garraway
- Departments of Surgery and Critical Care Medicine, University of British Columbia, Vancouver, BC Canada
| | - Massimo Sartelli
- Department of Surgery, Macerata Hospital, Global Alliance for Infections in Surgery, Macerata, Italy
| | - Chad G. Ball
- Trauma and Acute Care Surgery, Foothills Medical Center, Calgary, AB Canada
| | - Neil G. Parry
- Departments of Surgery and Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON Canada
| | - Kelly Voght
- Departments of Surgery and Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON Canada
| | - Lisa Julien
- Department of Surgery, NSHA-Queen Elizabeth II Health Sciences Center, Dalhousie University, Halifax, NS Canada
| | - Jenna Kroeker
- Departments of Surgery and Critical Care Medicine, University of British Columbia, Vancouver, BC Canada
| | - Derek J. Roberts
- Division of Vascular and Endovascular Surgery, Department of Surgery and School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, ON Canada
| | | | | | - Ernest E. Moore
- Ernest E. Moore Shock Trauma Center, University of Colorado, Denver, CO USA
| | | | - Elissavet Anestiadou
- 4th Department of Surgery, Medical School, Aristotle University of Thessaloniki, General Hospital “George Papanikolaou”, Thessaloniki, Greece
| | | | - Konstantinos Bouliaris
- General Surgery Department of Koutlimbaneio, Triantafylleio General Hospital of Larissa, Larissa, Thessaly Greece
| | | | - Marco Ceresoli
- General and Emergency Surgery, School of Medicine and Surgery, Milano-Bicocca University, Monza, Italy
| | - Francesco Favi
- Chirurgia Generale E d’Urgenza, Ospedale M. Bufalini - Cesena, AUSL Della Romagna, Cesena, Italy
| | - Angela Gurrado
- Department of Precision and Regenerative Medicine and Ionian Area, Unit of Academic General Surgery “V. Bonomo”, University of Bari “A. Moro”, Bari, Italy
| | - Joao Rezende-Neto
- Trauma and Acute Care Surgery, General Surgery, St. Michael’s Hospital, Toronto, ON Canada
| | - Arda Isik
- General Surgery Department, Istanbul Medeniyet University School of Medicine Istanbul, Istanbul, Turkey
| | - Camilla Cremonini
- Emergency Surgery and Trauma Center, University of Pisa, Pisa, Italy
| | - Silivia Strambi
- Emergency Surgery and Trauma Center, University of Pisa, Pisa, Italy
| | - Georgios Koukoulis
- General Surgery Department of Koutlimbaneio, Triantafylleio General Hospital of Larissa, Larissa, Thessaly Greece
| | - Mario Testini
- Department of Precision and Regenerative Medicine and Ionian Area, Unit of Academic General Surgery “V. Bonomo”, University of Bari “A. Moro”, Bari, Italy
| | - Sandy Trpcic
- Trauma and Acute Care Surgery, General Surgery, St. Michael’s Hospital, Toronto, ON Canada
| | - Alessandro Pasculli
- Department of Precision and Regenerative Medicine and Ionian Area, Unit of Academic General Surgery “V. Bonomo”, University of Bari “A. Moro”, Bari, Italy
| | - Erika Picariello
- General Surgery Unit, Ospedale M. Buffalini Di Cesena, Cesena, Italy
| | - Fikri Abu-Zidan
- College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates
| | - Ademola Adeyeye
- Division of Surgical Oncology, Afe Babalola University Multisystem Hospital, Ado-Ekiti, Nigeria
| | - Goran Augustin
- University Hospital Centre Zagreb, School of Medicine University of Zagreb, Zagreb, Croatia
| | - Felipe Alconchel
- Virgen de la Arrixaca University Hospital IMIB-Arrixaca, Ctra. Madrid-Cartagena, S/N, Murcia, Spain
| | - Yuksel Altinel
- Bagcilar Research and Training Hospital, Istanbul, Turkey
| | - Luz Adriana Hernandez Amin
- Nurse Master of Nursing, Professor and Coordinator of the teaching-service relationship, Faculty of Health Sciences, University of Sucre, Sincelejo, Colombia
| | - José Manuel Aranda-Narváez
- Trauma and Emergency Surgery Unit. General, Digestive and Transplantation Surgery Department, University Regional Hospital of Málaga, Malaga, Spain
| | | | | | - Gian Luca Baiocchi
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Luigi Bonavina
- Department of Surgery, University of Milan Medical School, Milan, Italy
| | - Giuseppe Brisinda
- Department of Surgery, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy
| | - Luca Cardinali
- Department of Surgery, General Hospital Madonna del Soccorso, San Benedetto del Tronto, Italy
| | - Andrea Celotti
- General Surgery Unit, UO Chirurgia Generale - Ospedale Maggiore Di Cremona, Cremona, Italy
| | - Mohamed Chaouch
- Department of Visceral and Digestive Surgery, Monastir University, Monastir, Tunisia
| | - Maria Chiarello
- Department of Surgery, Azienda Sanitaria Provinciale Di Cosenza, Cosenza, Italy
| | - Gianluca Costa
- Fondazione Policlinico Campus Bio-Medico, University Campus Bio-Medico of Rome, Rome, Italy
| | - Nicola de’Angelis
- Colorectal and Digestive Surgery Unit–DIGEST Department, Beaujon University Hospital AP-HP, University Paris Cité, Clichy, France
| | - Nicolo De Manzini
- Department of General Surgery, Cattinara University Hospital, Trieste, Italy
| | - Samir Delibegovic
- Department of Proctology, Clinic for Surgery, University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina
| | - Salomone Di Saverio
- Department of General Surgery, University of Insubria, University Hospital of Varese, ASST Sette Laghi, Regione Lombardia, Italy
| | - Belinda De Simone
- Unit of Digestive and Metabolic Minimally Invasive Surgery, Clinique Saint Louis, Poissy, Poissy, Ile de France, France
- Unit of Emergency and General Surgery, Guastalla Hospital, AUSL Reggio Emilia, Guastalla, Italy
| | - Vincent Dubuisson
- Chirurgie Digestive, Service de Chirurgie Vasculaire Et, Générale University Hospital of Bordeaux FR, Bordeaux, France
| | | | | | - Alessio Giordano
- Emergency and General Consultant Surgeon, Nuovo Ospedale “S. Stefano”, Azienda ASL Toscana Centro, Prato, Italy
| | - Carlos Gomes
- Surgery Unit, Hospital Universitário Terezinha de Jesus, SUPREMA, Juiz de Fora, Brazil
| | - Firdaus Hayati
- Department of Surgery, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu, Sabah, Malaysia
| | - Jinjian Huang
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu China
| | | | | | | | - Mansoor Khan
- General Surgery, University Hospitals, Sussex, UK
| | | | - Manu L. N. G. Malbrain
- First Department of Anaesthesiology and Intensive Therapy, Medical University of Lublin, Lublin, Poland
- International Fluid Academy, Lovenjoel, Belgium
| | - Sanjay Marwah
- Postgraduate Institute of Medical Sciences, Rohtak, Haryana India
| | | | | | - Alessia Morello
- Department of General Surgery, Madonna del Soccorso Hospital - San Benedetto del Tronto, Italy, Italy
| | - Francesk Mulita
- Department of Surgery, General University Hospital of Patras, Rio, Greece
| | - Valentina Murzi
- Department of Surgical Science, Cagliari State University, Cagliari, Italy
| | | | | | - Ajay Pak
- Department of General Surgery, King George’s Medical University, Lucknow, UP India
| | - Michael Pak-Kai Wong
- School of Medical Sciences & Hospital, Universiti Sains Malaysia, Kelantan, Malaysia
| | | | - Mauro Podda
- Department of Emergency Surgery, Cagliari University Hospital, Cagliari, Italy
| | - Caterina Puccioni
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of Sacred Heart, Rome, Italy
| | - Kemal Rasa
- Department of General Surgery, Hüseyin Kemal Raşa, Anadolu Medical Center, Kocaeli, Turkey
| | - Jianan Ren
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu China
| | - Francesco Roscio
- Division of General and Minimally Invasive Surgery, ASST Valle Olona, Busto Arsizio, Italy
| | - Antonio Gonzalez-Sanchez
- Trauma and Emergency Surgery Unit. General, Digestive and Transplantation Surgery Department, University Regional Hospital of Málaga, Malaga, Spain
| | - Gabriele Sganga
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of Sacred Heart, Rome, Italy
| | - Maximilian Scheiterle
- Emergency Surgery Unit and Trauma Team, Careggi University Hospital, Florence, Italy
| | | | - Dmitry Smirnov
- Department of Surgery, South Ural State Medical University, Chelyabinsk City, Russia
| | - Lorenzo Tosi
- Department of General Surgery, University of Bologna, Bologna, Italy
| | | | | | | | - Sofia Xenaki
- Department of General Surgery, University Hospital of Heraklion, Crete, Greece
| | | | - Xiuwen Wu
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu China
| | - Andee Dzulkarnean Zakaria
- Department of Surgery, School of Medical Sciences and Hospital USM, Universiti Sains Malaysia, Georgetown, Malaysia
| | - Zaidi Zakaria
- Department of Surgery, School of Medical Sciences and Hospital USM, Universiti Sains Malaysia, Georgetown, Malaysia
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Kapoor I, Prabhakar H, Mahajan C, Zirpe KG, Tripathy S, Wanchoo J, Kakkar G, Sapra H, Gupta N, Singhal V, Chaturvedi A. A Nationwide Survey on the Practice of End-of-life Care Issues in Critical Care Units in India. Indian J Crit Care Med 2023; 27:305-314. [PMID: 37214124 PMCID: PMC10196640 DOI: 10.5005/jp-journals-10071-24446] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 03/23/2023] [Indexed: 05/24/2023] Open
Abstract
Background End-of-life (EOL) care is the care of terminally ill patients who are nearing their end. It includes important components like palliative care, supportive care, hospice care, patient's right to choose, and choice of medical intervention, including continuation of routine medical interventions. The aim of this survey was to assess the practices of EOL care in various critical care units in India. Methods The participants included clinicians involved in EOL care of patients with advanced diseases in different hospital across India. We sent blast emails and posted links on social media for inviting participants to take the survey. Study data were collected and managed by using Google Forms. The collected information was automatically entered into a spread sheet and stored in a secure database. Results In total, 91 clinicians took the survey. The years of experience, practice area, and setting had significant effect on the palliative care, terminal strategy, and prognostication in terminally ill patients (p < 0.05). Statistical analysis was done using software STATA. Descriptive statistics were performed, and results were presented as number (percentage). Conclusion The years of work experience, the practice area, and the practice setting have a strong impact on EOL care management of terminally ill patients. There are a lot of gaps in providing EOL care for these patients. Many reforms are needed in the Indian health care system to make EOL care better. How to cite this article Kapoor I, Prabhakar H, Mahajan C, Zirpe KG, Tripathy S, Wanchoo J, et al. A Nationwide Survey on the Practice of End-of-life Care Issues in Critical Care Units in India. Indian J Crit Care Med 2023;27(5):305-314.
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Affiliation(s)
- Indu Kapoor
- Department of Neuroanaesthesiology and Critical Care, All India Institute of Medical Sciences, New Delhi, India
| | - Hemanshu Prabhakar
- Department of Neuroanaesthesiology and Critical Care, All India Institute of Medical Sciences, New Delhi, India
| | - Charu Mahajan
- Department of Neuroanaesthesiology and Critical Care, All India Institute of Medical Sciences, New Delhi, India
| | | | - Swagata Tripathy
- Department of Anesthesia and Intensive Care, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
| | - Jaya Wanchoo
- Department of Neuroanaesthesia and Neurocritical Care, Medanta The Medicity, Gurgaon, Haryana, India
| | - Gaurav Kakkar
- Department of Neuroanaesthesia and Neurocritical Care, Amrita Hospital, Faridabad, India
| | - Harsh Sapra
- Department of Neuroanaesthesia and Neurocritical Care, Medanta The Medicity, Gurgaon, Haryana, India
| | - Nidhi Gupta
- Department of Neuroanaesthesia, Indraprastha Apollo Hospital, New Delhi, India
| | - Vasudha Singhal
- Department of Neuroanaesthesia and Neurocritical Care, Medanta The Medicity, Gurgaon, Haryana, India
| | - Arvind Chaturvedi
- Department of Neuroanaesthesiology and Critical Care, All India Institute of Medical Sciences, New Delhi, India
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Author's response: "Combination of norepinephrine with phenylephrine versus norepinephrine with vasopressin in critically ill patients with septic shock: A retrospective study". J Crit Care 2023; 74:154240. [PMID: 36543618 DOI: 10.1016/j.jcrc.2022.154240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Accepted: 12/12/2022] [Indexed: 12/23/2022]
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Wang L, Wang M, Du J, Gong ZC. Intensive insulin therapy in sepsis patients: Better data enables better intervention. Heliyon 2023; 9:e14063. [PMID: 36915524 PMCID: PMC10006498 DOI: 10.1016/j.heliyon.2023.e14063] [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: 08/18/2022] [Revised: 02/10/2023] [Accepted: 02/20/2023] [Indexed: 02/26/2023] Open
Abstract
In clinics, sepsis is a critical disease that often develops into shock and multiple organ dysfunction, leading to a serious threat of death. Patients with sepsis are often accompanied by stress hyperglycemia which is an independent risk factor for poor prognosis in sepsis. Thus, the treatment for stress hyperglycemia has attracted more and more attention, among which intensive insulin therapy is widely concerned. However, the benefits and harms of intensive insulin therapy for sepsis patients remain controversial. What the existing literature discusses mostly are the clinical benefit and hypoglycemia risk of intensive insulin therapy, but there is no conclusion on the target range of blood glucose control, the applicable patients, the timing of treatment initiation, and how to avoid the risk. In this study, we have analyzed and summarized the existing literature, hoping to determine the adverse and clinical benefit of intensive insulin therapy in sepsis. And we attempt to assemble better evidence to propose a better recommendation on hyperglycemia intervention for sepsis patients.
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Affiliation(s)
- Ling Wang
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China
| | - Min Wang
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China.,Hunan Clinical Research Center for Clinical Pharmacy, Xiangya Hospital, Central South University, Changsha, China
| | - Jie Du
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China.,Hunan Clinical Research Center for Clinical Pharmacy, Xiangya Hospital, Central South University, Changsha, China
| | - Zhi-Cheng Gong
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China.,Hunan Clinical Research Center for Clinical Pharmacy, Xiangya Hospital, Central South University, Changsha, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
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Li L, Shi X, Xiong M, Kong K, Chen Z, Zhou S, Zeng Z, An S, Xu B. Dexmedetomidine only regimen for long-term sedation is associated with reduced vasopressor requirements in septic shock patients: A retrospective cohort study from MIMIC-IV database. Front Med (Lausanne) 2023; 10:1107251. [PMID: 36923011 PMCID: PMC10010261 DOI: 10.3389/fmed.2023.1107251] [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: 11/24/2022] [Accepted: 02/03/2023] [Indexed: 03/02/2023] Open
Abstract
Background Previous studies have shown that dexmedetomidine (DEX) may be associated with reduced vasopressor requirements in septic shock patients, however, long-term DEX-only sedation in reducing vasopressor requirements is still controversial. Methods A retrospective study was conducted among patients with septic shock on mechanical ventilation using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The primary outcome was the ratio of norepinephrine equivalent dose to mean arterial pressure (NEq/MAP) in the first 72 h after DEX or other sedatives for sedation. The secondary outcomes were key organ function parameters, 28-day mortality, and 90-day mortality. Univariate, propensity score matching (PSM), and generalized linear mixed model (GLMM) analyses were performed. Results DEX was associated with decreased NEq/MAP in the first 72 h (difference = 0.05, 95% CI = -0.02-0.08, p = 0.002) after adjusting for confounders in the GLMM analysis. The DEX group was also associated with a lower heart rate, cardiac output (CO), lactate level, aspartate transaminase (AST) level, and higher PaO2/FiO2 ratio (p < 0.0125). Moreover, DEX only sedation was associated with reduced 90-day mortality (OR = 0.60, 95% CI = 0.37-0.94, p = 0.030). Conclusion DEX may be associated with decreased vasopressor requirements, improved AST and PaO2/FiO2 levels, and reduced 90-day mortality in patients with septic shock, which warrants further study.
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Affiliation(s)
- Lulan Li
- Department of Anesthesiology, General Hospital of Southern Theatre Command of PLA, The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xiaotong Shi
- Department of Biostatistics, School of Public Health (Guangdong Provincial Key Laboratory of Tropical Disease Research), Southern Medical University, Guangzhou, Guangdong, China
| | - Ming Xiong
- Department of Anesthesiology & Peri-Operative Medicine, New Jersey Medical School, Rutgers, United States
| | - Karen Kong
- Department of Anesthesiology & Peri-Operative Medicine, New Jersey Medical School, Rutgers, United States
| | - Zhongqing Chen
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Shiyu Zhou
- Department of Biostatistics, School of Public Health (Guangdong Provincial Key Laboratory of Tropical Disease Research), Southern Medical University, Guangzhou, Guangdong, China
| | - Zhenhua Zeng
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Shengli An
- Department of Biostatistics, School of Public Health (Guangdong Provincial Key Laboratory of Tropical Disease Research), Southern Medical University, Guangzhou, Guangdong, China
| | - Bo Xu
- Department of Anesthesiology, General Hospital of Southern Theatre Command of PLA, The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
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Arishi H, AlQahtani S, Sadat M, Arabi YM. Author reply: Combination of norepinephrine with phenylephrine versus norepinephrine with vasopressin in critically ill patients with septic shock: A retrospective study. J Crit Care 2023; 73:154176. [PMID: 36266194 DOI: 10.1016/j.jcrc.2022.154176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Accepted: 10/10/2022] [Indexed: 12/12/2022]
Affiliation(s)
- Hatim Arishi
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; Intensive Care Department, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
| | - Samah AlQahtani
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; Intensive Care Department, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Musharaf Sadat
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; Intensive Care Department, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
| | - Yaseen M Arabi
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; Intensive Care Department, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
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Xian J, Wang L, Zhang C, Wang J, Zhu Y, Yu H, Zhang X, Tan Q. Efficacy and safety of acupuncture as a complementary therapy for sepsis: a systematic review and meta-analysis. Acupunct Med 2023; 41:3-15. [PMID: 35579024 DOI: 10.1177/09645284221086288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND Sepsis is a life-threatening organ dysfunction caused by dysregulation of the host response to infection. Acupuncture is used for treatment of inflammatory diseases; however, its effectiveness and safety as a complementary therapy for sepsis has not been fully explored. METHODS Data were retrieved from eight databases. Randomized controlled trials (RCTs) that compared acupuncture plus conventional therapies versus conventional therapies alone were included. Pre-specified primary outcomes were mortality at 28 days and Acute Physiologic and Chronic Health Evaluation (APACHE) II scores. RESULTS A total of 17 studies with 1099 participants were included in this study. In terms of the primary outcomes, acupuncture plus routine therapy reduced mortality at 28 days (risk ratio (RR)): 0.69, 95% confidence interval (CI): 0.52 to 0.91, p < 0.001) and APACHE II scores (mean difference (MD): -2.84, 95% CI: -4.09 to -1.58, p < 0.001) at day 7 after treatment compared with routine therapy alone. In terms of secondary outcomes, acupuncture plus routine therapy reduced white blood cell counts and levels of procalcitonin (PCT), tumor necrosis factor (TNF)-α, interleukin (IL)-6 and lactic acid and intra-abdominal pressure (IAP), and improved CD3+, CD4+ and monocytes of human leukocyte antigen (HLA)-DR at day 7 after treatment compared with routine therapy alone. However, acupuncture plus routine therapy had no significant effects on levels of IL-10, C-reactive protein (CRP), CD8+ and CD4+/CD8+ ratios compared with routine therapy alone. Quality of evidence was low to very low for all parameters (GRADE). CONCLUSION The available evidence showed that combination of acupuncture and routine therapy may have benefit for sepsis compared with use of routine therapy only. Due to the low degree of certainty regarding its effects, further research is required. TRIAL REGISTRATION NUMBER ICRD42019141491 (PROSPERO).
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Affiliation(s)
- Jin Xian
- Shandong University of Traditional Chinese Medicine, Jinan, China.,Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Ling Wang
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Changyun Zhang
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Jian Wang
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yushuo Zhu
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Huijuan Yu
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xin Zhang
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Qiwen Tan
- Shandong University of Traditional Chinese Medicine, Jinan, China
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Huang D, Ma J, Wang S, Qin T, Song F, Hou T, Ma H. Changes of cardiac output and velocity time integral in blood return at the end of renal replacement therapy predict fluid responsiveness in critically Ill patients with acute circulatory failure. BMC Anesthesiol 2023; 23:25. [PMID: 36639628 PMCID: PMC9840273 DOI: 10.1186/s12871-023-01976-7] [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: 04/21/2022] [Accepted: 01/05/2023] [Indexed: 01/15/2023] Open
Abstract
OBJECTIVES To observe if blood return, also defined as the blood infusion test (BIT) could predict fluid responsiveness in critically ill patients with acute circulatory failure and renal replacement therapy (RRT). METHODS This was a single-center, prospective, diagnostic accuracy study. Before BIT, the passive leg raise test (PLRT) was performed to record the change of cardiac output (ΔCO) by pulse contour analysis, and ΔCO > = 10% was defined as the fluid responder. Meanwhile, the change in velocity time integral (ΔVTI) was recorded by ultrasound. Later, the ΔCO and ΔVTI during BIT were recorded 5-10 min after PLRT. The receiver-operating characteristic curves of ΔCO and ΔVTI of BIT were performed in predicting the fluid responder defined by PLRT. RESULTS A total of 43 patients with acute circulatory failure undergoing RRT were enrolled in the present study, and 25 patients (58.1%) were recognized as responders during PLRT. According to the receiver-operating characteristic curves, the cutoff value of ΔCO was 10% and ΔVTI was 9% during BIT with the area under curve of 0.96 and 0.94, respectively. CONCLUSIONS BIT in RRT could identify fluid responsiveness in critically ill patients with shock. TRIAL REGISTRATION ChiCTR-DDD-17010534. Registered on 30/01/2017 (retrospective registration).
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Affiliation(s)
- Daozheng Huang
- Department of Critical Care Medicine, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080 China ,Medical Department, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080 China
| | - Jie Ma
- grid.459671.80000 0004 1804 5346Department of Critical Care Medicine, Jiangmen Central Hospital, Jiangmen, 529000 China
| | - Shouhong Wang
- Department of Critical Care Medicine, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080 China
| | - Tiehe Qin
- Department of Critical Care Medicine, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080 China
| | - Feier Song
- grid.284723.80000 0000 8877 7471The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510080 China ,Department of Emergency Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080 China
| | - Tieying Hou
- Medical Department, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080 China ,Guangdong Clinical Laboratory Center, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080 China
| | - Huan Ma
- Department of Critical Care Medicine, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080 China
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Eshghi F, Tahmasebi S, Alimohammadi M, Soudi S, Khaligh SG, Khosrojerdi A, Heidari N, Hashemi SM. Study of immunomodulatory effects of mesenchymal stem cell-derived exosomes in a mouse model of LPS induced systemic inflammation. Life Sci 2022; 310:120938. [PMID: 36150466 DOI: 10.1016/j.lfs.2022.120938] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 08/19/2022] [Accepted: 09/04/2022] [Indexed: 11/09/2022]
Abstract
BACKGROUND Sepsis is a debilitating systemic inflammation that resulted from infection or injury. Despite many advances in treatment, the resulting mortality rate has remained high due to increasing antibiotic resistance and aging communities. The present study investigated the effects of stem cell-derived exosomes in a mouse model of LPS-induced systemic inflammation. MATERIALS AND METHODS To induce sepsis, the LPS model was used. Mice were divided into three groups: normal, patient group (LPS + PBS), and treatment group (LPS + exosome). The treatment group received an intravenous exosome 1 h after induction of the model. Patient and treatment groups were sacrificed at 4, 6, 24, and 48 h after induction of the model, and their tissues were isolated. Blood samples were taken from animal hearts to perform biochemical and immunological tests. The study results were analyzed using Graph Pad Prism software version 9. RESULTS Mesenchymal stem cell-derived exosomes decreased serum levels of ALT and AST liver enzymes, decreased neutrophil to lymphocyte ratio (NLR), and improved kidney, liver, and lung tissue damage at 4, 6, and 24 h after model induction. At 24 h, the exosomes were able to reduce serum urea levels. This study revealed decreased levels of inflammatory cytokines such as IL-6, IL-1β, and TNF-α after exosome injection. CONCLUSION Our findings suggest that treating mice with stem cell-derived exosomes can ameliorate the destructive effects of inflammation caused by sepsis by reducing inflammatory factors and tissue damage.
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Affiliation(s)
- Fateme Eshghi
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Safa Tahmasebi
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mina Alimohammadi
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sara Soudi
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | | | - Arezou Khosrojerdi
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Neda Heidari
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Mahmoud Hashemi
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Medical Nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Messina A, Bakker J, Chew M, De Backer D, Hamzaoui O, Hernandez G, Myatra SN, Monnet X, Ostermann M, Pinsky M, Teboul JL, Cecconi M. Pathophysiology of fluid administration in critically ill patients. Intensive Care Med Exp 2022; 10:46. [PMID: 36329266 PMCID: PMC9633880 DOI: 10.1186/s40635-022-00473-4] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Accepted: 10/17/2022] [Indexed: 11/06/2022] Open
Abstract
Fluid administration is a cornerstone of treatment of critically ill patients. The aim of this review is to reappraise the pathophysiology of fluid therapy, considering the mechanisms related to the interplay of flow and pressure variables, the systemic response to the shock syndrome, the effects of different types of fluids administered and the concept of preload dependency responsiveness. In this context, the relationship between preload, stroke volume (SV) and fluid administration is that the volume infused has to be large enough to increase the driving pressure for venous return, and that the resulting increase in end-diastolic volume produces an increase in SV only if both ventricles are operating on the steep part of the curve. As a consequence, fluids should be given as drugs and, accordingly, the dose and the rate of administration impact on the final outcome. Titrating fluid therapy in terms of overall volume infused but also considering the type of fluid used is a key component of fluid resuscitation. A single, reliable, and feasible physiological or biochemical parameter to define the balance between the changes in SV and oxygen delivery (i.e., coupling "macro" and "micro" circulation) is still not available, making the diagnosis of acute circulatory dysfunction primarily clinical.
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Affiliation(s)
- Antonio Messina
- IRCCS Humanitas Research Hospital, Via Alessandro Manzoni 56, Rozzano, 20089, Milan, Italy.
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
| | - Jan Bakker
- NYU Langone Health and Columbia University Irving Medical Center, New York, USA
- Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Michelle Chew
- Department of Anaesthesia and Intensive Care, Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Daniel De Backer
- Department of Intensive Care, CHIREC Hospitals, Université Libre de Bruxelles, Brussels, Belgium
| | - Olfa Hamzaoui
- Service de Reanimation PolyvalenteHopital Antoine Béclère, Hopitaux Universitaires Paris-Saclay, Clamart, France
| | - Glenn Hernandez
- Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Sheila Nainan Myatra
- Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
| | - Xavier Monnet
- Hôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Medical Intensive Care Unit, Le Kremlin-Bicêtre, Paris, France
| | - Marlies Ostermann
- Department of Intensive Care, King's College London, Guy's & St Thomas' Hospital, London, UK
| | - Michael Pinsky
- Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Jean-Louis Teboul
- Hôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Medical Intensive Care Unit, Le Kremlin-Bicêtre, Paris, France
| | - Maurizio Cecconi
- IRCCS Humanitas Research Hospital, Via Alessandro Manzoni 56, Rozzano, 20089, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
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48
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Spiegel R, Hockstein M, Waters J, Goyal M. The Survival of the Surviving Sepsis Campaign. Med Clin North Am 2022; 106:1109-1117. [PMID: 36280336 DOI: 10.1016/j.mcna.2022.08.006] [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: 10/31/2022]
Abstract
Even well-intentioned policies have great potential to cause harm. This statement is vividly illustrated by the influential, yet controversial, Surviving Sepsis Campaign guidelines and subsequent CMS benchmarks. Despite low-quality evidence, tendentious industry ties, and rebuke from the Infectious Disease Society of America (IDSA), these benchmarks continue to eschew therapy driven by clinician expertise and individual patient needs in favor of mandating an arbitrary, one-size-fits-all approach that suspends clinical judgment and promotes indiscriminate use of treatments that have the potential to cause great harm.
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Affiliation(s)
- Rory Spiegel
- Department of Emergency Medicine, Medstar Washington Hospital Center, 110 Irving St, Washington, DC 20010, USA; Department of Critical Care Medicine, Medstar Washington Hospital Center, Washington, DC 20010, USA.
| | - Max Hockstein
- Department of Emergency Medicine, Medstar Washington Hospital Center, 110 Irving St, Washington, DC 20010, USA; Department of Critical Care Medicine, Medstar Washington Hospital Center, Washington, DC 20010, USA
| | - Jessica Waters
- Department of Emergency Medicine, Medstar Washington Hospital Center, 110 Irving St, Washington, DC 20010, USA
| | - Munish Goyal
- Department of Emergency Medicine, Medstar Washington Hospital Center, 110 Irving St, Washington, DC 20010, USA
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Ganguli A, Lim J, Mostafa A, Saavedra C, Rayabharam A, Aluru NR, Wester M, White KC, Kumar J, McGuffin R, Frederick A, Valera E, Bashir R. A culture-free biphasic approach for sensitive and rapid detection of pathogens in dried whole-blood matrix. Proc Natl Acad Sci U S A 2022; 119:e2209607119. [PMID: 36161889 PMCID: PMC9546527 DOI: 10.1073/pnas.2209607119] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 08/22/2022] [Indexed: 11/18/2022] Open
Abstract
Blood stream infections (BSIs) cause high mortality, and their rapid detection remains a significant diagnostic challenge. Timely and informed administration of antibiotics can significantly improve patient outcomes. However, blood culture, which takes up to 5 d for a negative result, followed by PCR remains the gold standard in diagnosing BSI. Here, we introduce a new approach to blood-based diagnostics where large blood volumes can be rapidly dried, resulting in inactivation of the inhibitory components in blood. Further thermal treatments then generate a physical microscale and nanoscale fluidic network inside the dried matrix to allow access to target nucleic acid. The amplification enzymes and primers initiate the reaction within the dried blood matrix through these networks, precluding any need for conventional nucleic acid purification. High heme background is confined to the solid phase, while amplicons are enriched in the clear supernatant (liquid phase), giving fluorescence change comparable to purified DNA reactions. We demonstrate single-molecule sensitivity using a loop-mediated isothermal amplification reaction in our platform and detect a broad spectrum of pathogens, including gram-positive methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteria, gram-negative Escherichia coli bacteria, and Candida albicans (fungus) from whole blood with a limit of detection (LOD) of 1.2 colony-forming units (CFU)/mL from 0.8 to 1 mL of starting blood volume. We validated our assay using 63 clinical samples (100% sensitivity and specificity) and significantly reduced sample-to-result time from over 20 h to <2.5 h. The reduction in instrumentation complexity and costs compared to blood culture and alternate molecular diagnostic platforms can have broad applications in healthcare systems in developed world and resource-limited settings.
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Affiliation(s)
- Anurup Ganguli
- Department of Bioengineering, University of Illinois at Urbana–Champaign, Urbana, IL-61801, USA
- Nick Holonyak Jr. Micro and Nanotechnology Laboratory, University of Illinois at Urbana–Champaign, Urbana, IL-61801, USA
| | - Jongwon Lim
- Department of Bioengineering, University of Illinois at Urbana–Champaign, Urbana, IL-61801, USA
- Nick Holonyak Jr. Micro and Nanotechnology Laboratory, University of Illinois at Urbana–Champaign, Urbana, IL-61801, USA
| | - Ariana Mostafa
- Department of Bioengineering, University of Illinois at Urbana–Champaign, Urbana, IL-61801, USA
- Nick Holonyak Jr. Micro and Nanotechnology Laboratory, University of Illinois at Urbana–Champaign, Urbana, IL-61801, USA
| | - Carlos Saavedra
- Nick Holonyak Jr. Micro and Nanotechnology Laboratory, University of Illinois at Urbana–Champaign, Urbana, IL-61801, USA
| | - Archith Rayabharam
- Department of Mechanical Science and Engineering, University of Illinois at Urbana–Champaign, Urbana, IL-61801, USA
| | - Narayana R. Aluru
- Department of Mechanical Science and Engineering, University of Illinois at Urbana–Champaign, Urbana, IL-61801, USA
| | - Matthew Wester
- Department of Bioengineering, University of Illinois at Urbana–Champaign, Urbana, IL-61801, USA
- Nick Holonyak Jr. Micro and Nanotechnology Laboratory, University of Illinois at Urbana–Champaign, Urbana, IL-61801, USA
| | - Karen C. White
- Critical Care, Carle Foundation Hospital, Urbana, IL-61801, USA
- Department of Clinical Science, Carle Illinois College of Medicine, Urbana, IL-61801, USA
| | - James Kumar
- Hospital Medicine, Carle Foundation Hospital, Urbana, IL-61801, USA
- Department of Clinical Science, Carle Illinois College of Medicine, Urbana, IL-61801, USA
| | - Reubin McGuffin
- Specimen Procurement Service Center in the Research Department, Carle Foundation Hospital, Urbana, IL-61801, USA
| | - Ann Frederick
- Microbiology, Carle Foundation Hospital, Urbana,IL-61801, USA
| | - Enrique Valera
- Department of Bioengineering, University of Illinois at Urbana–Champaign, Urbana, IL-61801, USA
- Nick Holonyak Jr. Micro and Nanotechnology Laboratory, University of Illinois at Urbana–Champaign, Urbana, IL-61801, USA
| | - Rashid Bashir
- Department of Bioengineering, University of Illinois at Urbana–Champaign, Urbana, IL-61801, USA
- Nick Holonyak Jr. Micro and Nanotechnology Laboratory, University of Illinois at Urbana–Champaign, Urbana, IL-61801, USA
- Department of Mechanical Science and Engineering, University of Illinois at Urbana–Champaign, Urbana, IL-61801, USA
- Department of Materials Science and Engineering, University of Illinois at Urbana–Champaign, Urbana, IL-61801, USA
- Department of Electrical and Computer Engineering, University of Illinois at Urbana–Champaign, Urbana, IL-61801,USA
- Department of Biomedical and Translational Science, Carle Illinois College of Medicine, Urbana, IL-61801, USA
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50
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Nakiganda C, Atukwatse J, Turyasingura J, Niyonzima V. Improving Nurses’ Knowledge on Sepsis Identification and Management at Mulago National Referral Hospital: A Quasi Experimental Study. NURSING: RESEARCH AND REVIEWS 2022. [DOI: 10.2147/nrr.s363072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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