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Fang Y, Dou A, Xie H, Zhang Y, Zhu W, Zhang Y, Li C, Su Y, Gao Y, Xie K. Association between renal mean perfusion pressure and prognosis in patients with sepsis-associated acute kidney injury: insights from the MIMIC IV database. Ren Fail 2025; 47:2449579. [PMID: 39780494 PMCID: PMC11722017 DOI: 10.1080/0886022x.2025.2449579] [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: 11/21/2024] [Revised: 12/21/2024] [Accepted: 12/31/2024] [Indexed: 01/11/2025] Open
Abstract
OBJECTIVE To investigate the association between renal mean perfusion pressure (MPP) and prognosis in sepsis-associated acute kidney injury (SA-AKI). METHODS Data were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Group-based trajectory modeling (GBTM) was applied to identify dynamic MPP patterns, while restricted cubic spline (RCS) curves were utilized to confirm the non-linear relationship between MPP and mortality. Cox regression analysis assessed the risk of mortality across different MPP levels, adjusting for potential confounders. Subgroup analyses and sensitivity analyses were conducted to ensure the robustness of the findings. RESULTS A total of 2318 patients with SA-AKI were stratified into five MPP trajectories by GBTM. Patients in Traj-1 and Traj-2, characterized by consistently low MPP (<60 mmHg), demonstrated markedly higher 90-d mortality (62.86% and 26.98%). RCS curves revealed a non-linear inverse relationship between MPP and 90-d mortality, identifying 60 mmHg as the optimal threshold. Patients with MPP ≤ 60 mmHg exhibited significantly elevated 90-d mortality compared to those with MPP > 60 mmHg (29.81% vs. 20.88%). Cox regression analysis established Traj-1 and Traj-2 as independent risk factors for increased mortality relative to Traj-3 (60-70 mmHg), with hazard ratios (HRs) of 4.67 (95%-CI 3.28-6.67) and 1.45 (95%-CI 1.20-1.76). MPP > 60 mmHg was significantly associated with reduced 90-d mortality (HR 0.65, 95%-CI 0.55-0.77). Subgroup and PSM analyses supported these findings. CONCLUSIONS Dynamic MPP trajectory serves as a valuable prognostic biomarker for SA-AKI. Early monitoring of MPP trends offers critical insights into renal perfusion management, potentially improving outcomes in SA-AKI.
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Affiliation(s)
- Yipeng Fang
- Department of Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China
| | - Aizhen Dou
- Department of Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China
| | - Hui Xie
- Firth Clinical College, XinXiang Medical University, Xinxiang, Henan, China
| | - Yunfei Zhang
- Editorial Department of Journal, Tianjin Hospital, Tianjin, China
| | - Weiwei Zhu
- Department of Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China
| | - Yingjin Zhang
- State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Caifeng Li
- Department of Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China
| | - Yanchao Su
- Department of Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China
| | - Ying Gao
- Department of Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China
| | - Keliang Xie
- Department of Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China
- Department of Anesthesiology, Tianjin Institute of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, China
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Ouyang L, Pan Y, Wu YF, Tang Q, Wang DF, Lou N. Early and high-volume administration of sodium bicarbonate in sepsis-associated acute kidney injury in patients with malignancies, during continuous renal replacement therapy. Ren Fail 2025; 47:2443026. [PMID: 39806784 PMCID: PMC11734398 DOI: 10.1080/0886022x.2024.2443026] [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: 07/28/2024] [Revised: 12/06/2024] [Accepted: 12/11/2024] [Indexed: 01/16/2025] Open
Abstract
INTRODUCTION Sepsis is an uncontrolled systemic response to infection that leads to life-threatening organ dysfunction. The in-hospital mortality rate remains significantly high in septic shock patients with malignancies. This study investigates whether early and high-volume administration of sodium bicarbonate during continuous renal replacement therapy (CRRT) can reduce 28-day mortality, increase shock reversal rates, and shorten the duration of CRRT, mechanical ventilation, and intensive care unit (ICU) stays. The goal is to provide valuable clinical data for the management of cancer patients with sepsis-associated acute kidney injury (SAKI). MATERIALS AND METHODS A retrospective study was performed on 88 patients who were admitted to the ICU and received continuous renal replacement therapy (CRRT) for acute renal failure secondary to sepsis at the Cancer Center of Sun Yat-sen University from March 2010 to October 2021. Based on the initiation time of CRRT and the volume of sodium bicarbonate infusion, patients were divided into four groups: the early high-volume group, early low-volume group, late high-volume group, and late low-volume group. RESULTS The results of this study showed that in the 28-day mortality model, established using the Cox proportional hazards method, early CRRT (HR 0.473; 95% CI 0.245-0.915, p = 0.026) and high-volume sodium bicarbonate infusion (HR 0.173; 95% CI 0.078-0.383, p < 0.001) were identified as two independent protective factors. The 28-day mortality rate in the early high-volume group (15.0%) was significantly lower than that of the other three groups (60.0%, 30.0%, and 75.0%, respectively; χ2 = 23.822, p < 0.001). Additionally, the shock reversal rate in the early high-volume group (80.0%) was significantly higher compared to the other groups (35.0%, 45.0%, and 35.7%; χ2 =13.576, p = 0.004). The duration of CRRT was shorter in the early high-volume group (35.0 ± 4.45 h) than in the other groups (70.0 ± 30.19 h, 48.0 ± 5.22 h, and 72.0 ± 19.84 h; χ2 =11.278, p = 0.01). Furthermore, the duration of mechanical ventilation (7.0 ± 3.33 days) was lower in the early high-volume group compared to the other groups (8.0 ± 1.12 days,10.0 ± 1.11 days, and 8.0 ± 2.65 days; χ2 =8.064, p = 0.045), as was the length of ICU stay (7.0 ± 0.89 days) compared to the other groups (13.0 ± 3.35 days, 10.0 ± 1.49 days, and10.0 ± 3.70 days; χ2 = 9.184, p = 0.027). CONCLUSION Early and high-volume administration of sodium bicarbonate during CRRT may reduce 28-day mortality and improve shock reversal rates in patients with sepsis-associated acute kidney injury complicated by malignancy. Prospective randomized controlled large sample studies are needed to confirm this.
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Affiliation(s)
- Lamei Ouyang
- Department of Critical Care Medicine, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R, China
- The Affiliated Guangdong Second Provincial General Hospital of Jinan University China, Guangzhou, P. R. China
| | - Yin Pan
- Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China
| | - Ya-Fei Wu
- Department of Critical Care Medicine, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R, China
- Department of Emergency, The First Affiliated Hospital of Ningbo University, Ningbo, P. R. China
| | - Qiang Tang
- Department of Critical Care Medicine, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R, China
| | - Dao-Feng Wang
- Department of Critical Care Medicine, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R, China
| | - Ning Lou
- Department of Critical Care Medicine, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R, China
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Mestriner F, Dantas PB, Michelon-Barbosa J, Dugaich VF, Luis-Silva F, Ribeiro MS, Evora PR, Becari C. Methylene blue as a potential intervention in sepsis: Effects on survival and microcirculation in rat models of sepsis. Biomed Pharmacother 2025; 187:118131. [PMID: 40349555 DOI: 10.1016/j.biopha.2025.118131] [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: 11/30/2024] [Revised: 05/02/2025] [Accepted: 05/05/2025] [Indexed: 05/14/2025] Open
Abstract
Sepsis is a life-threatening condition characterized by systemic inflammation and microcirculatory dysfunction. Methylene blue (MB), a compound with known antioxidant and anti-inflammatory properties, has been proposed as a potential therapeutic agent. This study aimed to investigate the effects of MB on survival rates and the preservation of mesenteric microcirculation in a rat model of endotoxemia. A total of 36 rats underwent cecal ligation and puncture (CLP) surgery to induce varying degrees of sepsis: mild (4 perforations), moderate (10 perforations), and severe (20 perforations). Animals received intravenous treatment with either MB (4 mg/kg) or saline. Survival was monitored for ten days. Additionally, intravital microscopy was used to assess leukocyte rolling and adhesion in mesenteric vessels following lipopolysaccharide (LPS)-induced sepsis. The experimental groups included saline, LPS + saline, MB + saline, LPS + MB, and MB + LPS. MB treatment significantly improved survival in the severe sepsis group, with a 30 % survival rate at ten days (p = 0.02, 95 % CI: 0.12-0.48), whereas all animals in the severe sepsis + saline group died within nine days. No significant survival benefit was observed in the mild and moderate sepsis groups (mild sepsis: p = 0.45, 95 % CI: 0.08-0.34; moderate sepsis: p = 0.32, 95 % CI: 0.15-0.51). In the LPS-induced model, treatment with both LPS and MB significantly reduced leukocyte rolling and adhesion (p < 0.001, 95 % CI: 0.45-0.75 for rolling; p < 0.03, 95 % CI: 0.30-0.60 for adhesion), with values comparable to those of the control group. In contrast, MB alone had no effect on leukocyte rolling or adhesion.In summary, MB significantly improved survival in severe sepsis and inhibited leukocyte migration in mesenteric vessels. These findings suggest that MB may protect the microcirculation and enhance survival under severe septic conditions, representing a promising therapeutic approach for sepsis management.
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Affiliation(s)
- Fabiola Mestriner
- Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Pedro Brüch Dantas
- Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Jessyca Michelon-Barbosa
- Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Vinicius Flora Dugaich
- Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Fabio Luis-Silva
- Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Department of Clinical Medicine, Barao de Maua University Center, University of Ribeirão Preto, São Paulo, Brazil
| | - Mauricio S Ribeiro
- Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Paulo R Evora
- Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Christiane Becari
- Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil.
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Nagalingam K, Whiting L, Farrington K, Migliozzi J, Pattison N. Clinical Assessment of Fluid Status in Adults With Acute Kidney Injury: A Scoping Review. J Ren Care 2025; 51:e70014. [PMID: 40186545 PMCID: PMC11971954 DOI: 10.1111/jorc.70014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 03/05/2025] [Accepted: 03/19/2025] [Indexed: 04/07/2025]
Abstract
BACKGROUND Acute kidney injury refers to sudden, potentially reversible, reduction in kidney function. Hypovolaemia is commonly the major risk factor. When acute kidney injury is established, fluid can accumulate leading to fluid overload. Undertaking a rigorous fluid assessment is vital in the management of a patient in hospital with acute kidney injury, as insufficient or excessive fluid can lead to increased morbidity and mortality. OBJECTIVES The aim of this scoping review is to identify which clinical assessments are useful when undertaking fluid assessment in a patient with acute kidney injury, and to identify signs and symptoms of fluid overload or dehydration in patients in hospital with acute kidney injury. DESIGN The JBI methodology for scoping reviews was followed and reported using the PRISMA-ScR checklist. PubMed, CINAHL Plus and SCOPUS were searched for research papers relating to the signs and symptoms or fluid assessments in patients with acute kidney injury. RESULTS Fifteen research papers were identified with four key areas being: Fluid balance/urine output and weight; early warning scores; clinical signs and symptoms; holistic assessment. The primary studies included in this scoping review have shown that hypovolaemia may be indicated by low blood pressure, orthostatic hypotension, low Mean Arterial Pressure, elevated heart rate, prolonged capillary refill time on the sternum (> 4.5 s) and subjectively reported cold peripheries. With clinical symptoms including dry mouth, increased thirst and dry skin. Accurate documentation of urine output and fluid balance is crucial in determining fluid status. CONCLUSION The assessment of fluid should be holistic and include history taking, diagnosis, blood tests and associated clinical signs and symptoms.
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Affiliation(s)
- Karen Nagalingam
- University of HertfordshireHatfieldUK
- Lister Hospital, East and North Hertfordshire NHS TrustStevenageUK
| | | | - Ken Farrington
- University of HertfordshireHatfieldUK
- Lister Hospital, East and North Hertfordshire NHS TrustStevenageUK
| | | | - Natalie Pattison
- University of HertfordshireHatfieldUK
- Lister Hospital, East and North Hertfordshire NHS TrustStevenageUK
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Scales DC, Rogowsky A, Burry L, Christenson J, Daneman N, Drennan IR, Hillier M, Jenneson S, Klein G, Mazzulli T, Moran P, Morris AM, Morrison LJ, Pinto R, Rubenfeld GD, Seymour CW, Stenstrom R, Verbeek PR, Cheskes S. Prehospital antibiotics and intravenous fluids for patients with sepsis: protocol for a 2×2 factorial randomised controlled trial. BMJ Open 2025; 15:e104257. [PMID: 40436458 PMCID: PMC12121580 DOI: 10.1136/bmjopen-2025-104257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2025] [Accepted: 05/09/2025] [Indexed: 06/01/2025] Open
Abstract
INTRODUCTION Prompt recognition and treatment of patients with sepsis improve survival. Patients transported to hospital with sepsis often do not receive treatment until they are assessed in emergency departments. Initiation of treatments by paramedics at the point of first contact may improve outcomes for these patients. METHODS AND ANALYSIS The study design involves two randomised controlled trials (RCTs) conducted using a 2×2 factorial design comparing use of (1) early intramuscular ceftriaxone versus placebo and (2) an early liberal intravenous fluid strategy (up to 2 L normal saline) versus usual care resuscitation guided by paramedic medical directives. Patients who are ≥18 years of age will be eligible for inclusion if they have sepsis, defined as (1) paramedic suspicion of infection, (2) fever (temperature ≥38.0°C measured by paramedic or history of fever during the previous 24 hours), and (3) hypotension: SBP <100 mm Hg. The primary outcome is mortality prior to hospital discharge or within 90 days of admission. Secondary outcomes are all-cause mortality at 90 days after enrolment; organ dysfunction during first 24 hours (mechanical ventilation, vasopressor therapy, dialysis) and hospitalisation (mechanical ventilation; dialysis); rates and duration of hospital admission; rates of ICU admission during index hospitalisation; discharge destination; proportion of patients with positive blood cultures obtained in hospital (first 24 hours); microbiological profile including distribution of microorganism species and resistant organisms; proportion of patients receiving additional antibiotics within 6 hours and within 24 hours of hospital admission; frequency distribution of first antibiotics (if any) delivered within 24 hours of hospital arrival; mean time to antibiotics delivered within 24 hours of hospital arrival (if any); proportion of patients receiving fluid bolus (>250 mL) within 24 hours of hospital arrival; total amount of crystalloid infused during transport and first 24 hours of hospitalisation; and proportion of enrolled patients not suspected to have sepsis or infection by emergency department physicians. Safety outcomes include the proportion of patients with pulmonary oedema during transport to hospital and on initial chest X-ray and the proportion of patients with anaphylaxis or suspected allergic reactions to study medication. ETHICS AND DISSEMINATION This study has been approved through Clinical Trials Ontario's streamlined ethics review process (board of record, Sunnybrook Health Sciences Centre). It will be conducted in accordance with the Declaration of Helsinki, Good Clinical Practice guidelines and regulatory requirements. The final results will be disseminated to participating paramedic services through educational materials, presentations and interactive training. We anticipate our trial will achieve wide dissemination through publication in a peer-reviewed medical journal and presentation at international conferences targeting the fields of prehospital and emergency medicine, resuscitation and critical care. TRIAL REGISTRATION NUMBER NCT03068741.
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Affiliation(s)
- Damon C Scales
- Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
- Interdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada
- Institute for Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
- ICES, Toronto, Ontario, Canada
| | - Anna Rogowsky
- Centre for Clinical Trial Support, Sunnybrook Research Institute, Toronto, Ontario, Canada
| | - Lisa Burry
- Interdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada
- Departments of Pharmacy and Medicine, Sinai Health System, Toronto, Ontario, Canada
- Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
| | - Jim Christenson
- Emergency Medicine, University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada
- Providence Research Institute, The University of British Columbia - Vancouver Campus, Vancouver, British Columbia, Canada
| | - Nick Daneman
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- Division of Infectious Diseases, Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Ian R Drennan
- Department of Family and Community Medicine, Division of Emergency Medicine, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- Ornge Critical Care Transport, Toronto, Ontario, Canada
| | - Morgan Hillier
- Department of Emergency Services, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
- Sunnybrook Centre for Prehospital Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
- Division of Emergency Medicine, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Sandra Jenneson
- The University of British Columbia - Vancouver Campus, Vancouver, British Columbia, Canada
| | - Gail Klein
- Centre for Clinical Trial Support, Sunnybrook Research Institute, Toronto, Ontario, Canada
| | - Tony Mazzulli
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
- Department of Microbiology, Sinai Health System, Toronto, Ontario, Canada
- Department of Microbiology, University Health Network, Toronto, Ontario, Canada
| | - Philip Moran
- Central East Prehospital Care Program, Lakeridge Health, Toronto, Ontario, Canada
| | - Andrew M Morris
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- Department of Medicine, Sinai Health, Toronto, Ontario, Canada
| | - Laurie J Morrison
- Institute for Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
- Department of Emergency Services, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
- Division of Emergency Medicine, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Ruxandra Pinto
- Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
- Interdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada
- Institute for Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
| | - Gordon D Rubenfeld
- Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
- Interdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada
- Institute for Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
| | | | - Rob Stenstrom
- University of British Columbia, Vancouver, British Columbia, Canada
- St Paul's Hospital, Vancouver, British Columbia, Canada
- Centre for Advancing Health Outcomes, Vancouver, British Columbia, Canada
- EmergencyCareBC, Vancouver, British Columbia, Canada
| | - P Richard Verbeek
- Department of Emergency Services, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
- Sunnybrook Centre for Prehospital Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
- Division of Emergency Medicine, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Sheldon Cheskes
- Sunnybrook Centre for Prehospital Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
- Department of Family and Community Medicine, Division of Emergency Medicine, University of Toronto, Toronto, Ontario, Canada
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Malic L, Zhang PGY, Plant PJ, Clime L, Nassif C, Da Fonte D, Haney EE, Moon BU, Sit VMS, Brassard D, Mounier M, Churcher E, Tsoporis JT, Falsafi R, Bains M, Baker A, Trahtemberg U, Lukic L, Marshall JC, Geissler M, Hancock REW, Veres T, Dos Santos CC. A machine learning and centrifugal microfluidics platform for bedside prediction of sepsis. Nat Commun 2025; 16:4442. [PMID: 40425547 PMCID: PMC12117141 DOI: 10.1038/s41467-025-59227-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Accepted: 04/15/2025] [Indexed: 05/29/2025] Open
Abstract
Sepsis is a life-threatening organ dysfunction due to a dysfunctional response to infection. Delays in diagnosis have substantial impact on survival. Herein, blood samples from 586 in-house patients with suspected sepsis are used in conjunction with machine learning and cross-validation to define a six-gene expression signature of immune cell reprogramming, termed Sepset, to predict clinical deterioration within the first 24 h (h) of clinical presentation. Prediction accuracy (~90% in early intensive care unit (ICU) and 70% in emergency room patients) is validated in 3178 patients from existing independent cohorts. A RT-PCR-based Sepset detection test shows a 94% sensitivity in 248 patients to predict worsening of the sequential organ failure assessment scores within the first 24 h. A stand-alone centrifugal microfluidic instrument that automates whole-blood Sepset classifier detection is tested, showing a sensitivity of 92%, and specificity of 89% in identifying the risk of clinical deterioration in patients with suspected sepsis.
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Affiliation(s)
- Lidija Malic
- Life Sciences Division, National Research Council of Canada, 75 de Mortagne Boulevard, Boucherville, QC, J4B 6Y4, Canada
- Center for Research and Applications in Fluidic Technologies (CRAFT), University of Toronto, 5 King's College Rd, Toronto, ON, M5S 1A8, Canada
- Department of Biomedical Engineering, McGill University, 775 Rue University, Suite 316, Montreal, QC, H3A 2B4, Canada
| | - Peter G Y Zhang
- Sepset Biosciences Inc., 420 - 730 View St, Victoria, BC, V8W 3S2, Canada
| | - Pamela J Plant
- Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Critical Care Medicine, 30 Bond Street, Toronto, ON, M5G 1W8, Canada
| | - Liviu Clime
- Life Sciences Division, National Research Council of Canada, 75 de Mortagne Boulevard, Boucherville, QC, J4B 6Y4, Canada
| | - Christina Nassif
- Life Sciences Division, National Research Council of Canada, 75 de Mortagne Boulevard, Boucherville, QC, J4B 6Y4, Canada
| | - Dillon Da Fonte
- Life Sciences Division, National Research Council of Canada, 75 de Mortagne Boulevard, Boucherville, QC, J4B 6Y4, Canada
| | - Evan E Haney
- Sepset Biosciences Inc., 420 - 730 View St, Victoria, BC, V8W 3S2, Canada
| | - Byeong-Ui Moon
- Life Sciences Division, National Research Council of Canada, 75 de Mortagne Boulevard, Boucherville, QC, J4B 6Y4, Canada
| | - Victor Min-Sung Sit
- Life Sciences Division, National Research Council of Canada, 75 de Mortagne Boulevard, Boucherville, QC, J4B 6Y4, Canada
| | - Daniel Brassard
- Life Sciences Division, National Research Council of Canada, 75 de Mortagne Boulevard, Boucherville, QC, J4B 6Y4, Canada
| | - Maxence Mounier
- Life Sciences Division, National Research Council of Canada, 75 de Mortagne Boulevard, Boucherville, QC, J4B 6Y4, Canada
| | - Eryn Churcher
- Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Critical Care Medicine, 30 Bond Street, Toronto, ON, M5G 1W8, Canada
| | - James T Tsoporis
- Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Critical Care Medicine, 30 Bond Street, Toronto, ON, M5G 1W8, Canada
| | - Reza Falsafi
- Centre for Microbial Diseases and Immunity Research, University of British Colombia, 232-2259 Lower Mall, Vancouver, BC, V6T 1Z4, Canada
| | - Manjeet Bains
- Centre for Microbial Diseases and Immunity Research, University of British Colombia, 232-2259 Lower Mall, Vancouver, BC, V6T 1Z4, Canada
| | - Andrew Baker
- Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Critical Care Medicine, 30 Bond Street, Toronto, ON, M5G 1W8, Canada
| | - Uriel Trahtemberg
- Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Critical Care Medicine, 30 Bond Street, Toronto, ON, M5G 1W8, Canada
- Department of Critical Care, Galilee Medical Center, Nahariya, Israel
- Medicine Faculty, Bar Ilan University, Zafed, Israel
| | - Ljuboje Lukic
- Life Sciences Division, National Research Council of Canada, 75 de Mortagne Boulevard, Boucherville, QC, J4B 6Y4, Canada
| | - John C Marshall
- Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Critical Care Medicine, 30 Bond Street, Toronto, ON, M5G 1W8, Canada
| | - Matthias Geissler
- Life Sciences Division, National Research Council of Canada, 75 de Mortagne Boulevard, Boucherville, QC, J4B 6Y4, Canada
| | - Robert E W Hancock
- Sepset Biosciences Inc., 420 - 730 View St, Victoria, BC, V8W 3S2, Canada
- Centre for Microbial Diseases and Immunity Research, University of British Colombia, 232-2259 Lower Mall, Vancouver, BC, V6T 1Z4, Canada
| | - Teodor Veres
- Life Sciences Division, National Research Council of Canada, 75 de Mortagne Boulevard, Boucherville, QC, J4B 6Y4, Canada
- Center for Research and Applications in Fluidic Technologies (CRAFT), University of Toronto, 5 King's College Rd, Toronto, ON, M5S 1A8, Canada
- Department of Mechanical and Industrial Engineering, University of Toronto, 5 King's College Road, Toronto, ON, M5S 3G8, Canada
| | - Claudia C Dos Santos
- Center for Research and Applications in Fluidic Technologies (CRAFT), University of Toronto, 5 King's College Rd, Toronto, ON, M5S 1A8, Canada.
- Sepset Biosciences Inc., 420 - 730 View St, Victoria, BC, V8W 3S2, Canada.
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Yu W, Yu S, Zhang F, Xu Q, Zhang X, Kong J. Ultrasensitive electrochemical sensor for lipopolysaccharide detection catalyzed by 3,4,9,10-perylenetetracarboxylic diimide. Anal Chim Acta 2025; 1352:343926. [PMID: 40210282 DOI: 10.1016/j.aca.2025.343926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 02/15/2025] [Accepted: 03/10/2025] [Indexed: 04/12/2025]
Abstract
BACKGROUND Lipopolysaccharide (LPS), a bacterial endotoxin prevalent in Gram-negative pathogens (e.g., Escherichia coli), induces severe immune responses linked to endotoxemia and hepatitis. Despite its clinical significance, conventional LPS detection methods (e.g., limulus amebocyte lysate assays) face challenges including operational complexity, high cost, and limited sensitivity. Addressing these limitations necessitates the development of innovative strategies for ultrasensitive LPS quantification. RESULTS We present an electrochemical biosensor integrating dual-signal amplification: (1) affinity amplification via phenylboronic acid-cis-diol covalent binding on LPS polysaccharide chains, and (2) photocatalytic amplification using perylene diimide (PDI)-mediated atom transfer radical polymerization (Photo-ATRP) under red light (615-650 nm). Thiol-functionalized DNA aptamers enable specific LPS capture, while PDI catalyzes rapid ferrocene monomer polymerization, achieving exponential signal enhancement. The sensor demonstrates exceptional performance: (1) Ultrahigh sensitivity: Detection limit of 0.25 fg/mL. (2) Wide dynamic range: Linear response from 1.0 fg/mL to 0.1 pg/mL. (3) Robust specificity: Minimal interference in human serum matrices. SIGNIFICANCE This work establishes a paradigm for LPS detection through three key advances: (1) Operational simplicity: Eliminates enzymatic/nanomaterial dependencies via metal-free PDI photocatalysis. (2) Translational utility: Serum compatibility supports clinical diagnostics and point-of-care applications. (3) Catalytic innovation: Validates PDI as a high-efficiency photocatalyst for controlled polymer synthesis. The sensor's low-cost fabrication, rapid response (<4.5 h), and femtomolar sensitivity position it as a transformative tool for sepsis monitoring and biomedical research.
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Affiliation(s)
- Wenjie Yu
- School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, 210094, PR China
| | - Shuaibing Yu
- School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, 210094, PR China
| | - Fenghong Zhang
- School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, 210094, PR China
| | - Qinyuan Xu
- School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, 210094, PR China
| | - Xueji Zhang
- School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen, 518060, PR China
| | - Jinming Kong
- School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, 210094, PR China.
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8
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He J, Shao Z, Li Z, He Y, Zhang J, Zhong H, Li J, Liu Q, Shao Y. Mechanistic Insights into HOTAIR-Driven ADAM17/NF-Κb Activation and Endothelial Dysfunction in LPS-Challenged HUVECs. Immunol Invest 2025:1-27. [PMID: 40366882 DOI: 10.1080/08820139.2025.2503174] [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: 05/16/2025]
Abstract
INTRODUCTION HOX transcript antisense intergenic RNA (HOTAIR) has been implicated in inflammation and vascular pathology, but its role in regulation of ADAM17 and sepsis-induced endothelial injury remains unclear. METHODS LPS-treated human umbilical vein endothelial cells (HUVECs) modeled sepsis-induced endothelial injury, which were assessed via qRT-PCR, western blot and immunofluorescence. HOTAIR-knockout mice were treated with cecal ligation and perforation to establish sepsis model. RESULTS LPS-stimulation increased expression of HOTAIR and ADAM17 and decreased miR-326 levels in HUVECs. HOTAIR-knockdown by antisense oligonucleotides (ASOs) decreased ADAM17, TNF-α production and NF-κB activities; it also alleviated endothelial inflammation, VE-cadherin integrity damage, apoptosis and barrier dysfunction, while miR-326 inhibition reversed these effects. MiR-326 inhibited TNF-α/NF-κB via targeting ADAM17. Further experiments demonstrated recombinant TNF-α reversed the inhibitory effect of HOTAIR-ASOs on LPS-triggered TNF-α/NF-κB activation and downstream endothelial injury, which were further mitigated by NF-κB or p38 MAPK inhibitors. In-vivo experiments in HOTAIR-knockout mice confirmed the role of HOTAIR/miR-326/ADAM17 in regulating NF-κB and p38 MAPK inflammation, with improved lung injury and survival following sepsis. DISCUSSION The HOTAIR/miR-326/ADAM17 axis is a key regulator of inflammation, endothelial injury and barrier dysfunction during sepsis via modulation of TNF-α/NF-κB signaling, providing new insights into the mechanisms underlying endothelial injury in sepsis.
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Affiliation(s)
- Junbing He
- The Department of Emergency, The First Affiliated Hospital, Jinan University, Guangzhou, GD, China
- Jieyang Medical Research Center, Jieyang People's Hospital, Jieyang Affiliated Hospital of Sun Yat-sen University, Jieyang, GD, China
| | - Zixuan Shao
- Dongguan Key Laboratory of Sepsis Translational Medicine, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, GD, China
| | - Zhuoji Li
- Dongguan Key Laboratory of Sepsis Translational Medicine, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, GD, China
| | - Yufu He
- Jieyang Medical Research Center, Jieyang People's Hospital, Jieyang Affiliated Hospital of Sun Yat-sen University, Jieyang, GD, China
| | - Jingqi Zhang
- Dongguan Key Laboratory of Sepsis Translational Medicine, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, GD, China
| | - Haotian Zhong
- Dongguan Key Laboratory of Sepsis Translational Medicine, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, GD, China
| | - Jiekai Li
- Jieyang Medical Research Center, Jieyang People's Hospital, Jieyang Affiliated Hospital of Sun Yat-sen University, Jieyang, GD, China
| | - Qinghua Liu
- Jieyang Medical Research Center, Jieyang People's Hospital, Jieyang Affiliated Hospital of Sun Yat-sen University, Jieyang, GD, China
- The Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, GD, China
| | - Yiming Shao
- The Department of Emergency, The First Affiliated Hospital, Jinan University, Guangzhou, GD, China
- Dongguan Key Laboratory of Sepsis Translational Medicine, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, GD, China
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9
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Lin S, Yan J, He S, Luo L. Identification of pyroptosis-related gene S100A12 as a potential diagnostic biomarker for sepsis through bioinformatics analysis and machine learning. Mol Immunol 2025; 183:44-55. [PMID: 40318597 DOI: 10.1016/j.molimm.2025.04.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 04/15/2025] [Accepted: 04/22/2025] [Indexed: 05/07/2025]
Abstract
Sepsis is a non-discriminatory inflammatory reaction that can result in a diverse array of organ dysfunctions, which can be fatal. Pyroptosis is a programmed mechanism of cell death that is distinguishable from apoptosis and other forms of cellular demise. However, the role of pyroptosis in sepsis remains to be further explored. In this study, by employing a combination of the difference analysis, WGCNA, Friends' analysis, and machine learning, the central gene S100A12 was successfully identified. S100A12 demonstrated superb diagnostic capabilities in both the integrated and external validation datasets. Furthermore, significant disparities were observed in the levels of monocytes, eosinophils, and neutrophils between sepsis patients and the control group, as per the findings of immune infiltration analysis. The aforementioned immune infiltrating cells exhibited an increase in expression levels among patients diagnosed with sepsis and were found to be significantly and positively associated with S100A12 expression. The results of the single-cell analysis indicated a significant expression of S100A12 in both neutrophils and monocytes, which was in complete alignment with the outcomes of immune infiltration. In summary, the pyroptosis-related gene S100A12 represents a potential biomarker for the diagnosis and treatment of sepsis.
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Affiliation(s)
- Shanshan Lin
- The First Clinical College, Guangdong Medical University, Zhanjiang, Guangdong 524023, China
| | - Jiayu Yan
- The First Clinical College, Guangdong Medical University, Zhanjiang, Guangdong 524023, China
| | - Shasha He
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Institute of Chinese Medicine, Beijing 100000, China.
| | - Lianxiang Luo
- The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, Guangdong 524023, China; The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang, Guangdong 524023, China.
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10
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Chung KP, Chen YH, Chen YJ, Chien JY, Kuo HC, Huang YT, Ruan SY, Lin YL, Chen YF, Keng LT, Kuo LC, Ku SC, Kuo CH, Yu CJ. INCREASED CIRCULATORY KREBS CYCLE METABOLITES IN SEPSIS IS ASSOCIATED WITH INCREASED INTERLEUKIN-6 RELEASE AND WORSE SURVIVAL. Shock 2025; 63:723-732. [PMID: 39836931 DOI: 10.1097/shk.0000000000002550] [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: 01/23/2025]
Abstract
ABSTRACT Objective : Recent studies have proposed that Krebs cycle metabolites may serve as potential biomarkers for prognosis in sepsis. However, whether these metabolites are associated with disease severity and can be applied to improve the effectiveness of current prognosis assessment in sepsis remains unclear and is explored in this study. Methods : This prospective multicenter cohort study was conducted in medical intensive care units (ICUs). From December 2019 to September 2022, consecutive patients admitted to medical ICUs for sepsis were screened and recruited. Plasma samples were obtained for measurements of cytokines and Krebs cycle metabolites, including citrate/isocitrate, cis-aconitate, alpha-ketoglutarate, succinate, fumarate, and malate. Results : In total, 97 patients admitted for sepsis were enrolled in the study. The 28-day mortality rate was 17.5%, and nonsurvivors exhibited significantly increased plasma lactate levels and Sequential Organ Failure Assessment (SOFA) scores. Plasma levels of Krebs cycle metabolites were significantly correlated with both plasma lactate and interleukin-6 levels. Except for citrate/isocitrate, all Krebs cycle metabolites were significantly elevated in patients with acute kidney injury. Multivariate Cox proportional hazard models, adjusted for plasma lactate levels and SOFA scores, revealed that plasma levels of alpha-ketoglutarate (adjusted hazard ratio [HR]: 2.404, P = 0.002), fumarate (adjusted HR: 1.904, P = 0.001) and malate (adjusted HR: 1.327, P = 0.019) were associated with increased risk of 28-day mortality. Conclusions : Study findings indicate that Krebs cycle metabolites, particularly alpha-ketoglutarate, fumarate, and malate, when applied with SOFA score, might enhance prognostic assessment in patients with sepsis.
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Affiliation(s)
| | | | - Yi-Jung Chen
- Department of Laboratory Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Jung-Yien Chien
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Han-Chun Kuo
- NTU Centers of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan
| | - Yen-Tsung Huang
- Institute of Statistical Science, Academia Sinica, Taipei, Taiwan
| | - Sheng-Yuan Ruan
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Yu-Li Lin
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Yen-Fu Chen
- Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
| | - Li-Ta Keng
- Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - Lu-Cheng Kuo
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Shih-Chi Ku
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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Bauer SR, Wieruszewski PM, Bissell Turpin BD, Dugar S, Sacha GL, Sato R, Siuba MT, Schleicher M, Vachharajani V, Falck-Ytter Y, Morgan RL. ADJUNCTIVE VASOPRESSORS AND SHORT-TERM MORTALITY IN ADULTS WITH SEPTIC SHOCK: A SYSTEMATIC REVIEW AND META-ANALYSIS. Shock 2025; 63:668-676. [PMID: 39965613 DOI: 10.1097/shk.0000000000002558] [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] [Indexed: 02/20/2025]
Abstract
ABSTRACT Background: Adjunctive vasopressors are added to norepinephrine in one-third of adults with septic shock in the United States. However, effectiveness of this approach is unclear, and treatment recommendations are based on indirect evidence. We sought to synthesize the direct evidence for adjunctive vasopressor administration in adults with septic shock. Methods: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to June 7, 2023. We included randomized clinical trials of adults with septic shock comparing adjunctive treatment with a vasopressin analogue, angiotensin II, methylene blue, hydroxocobalamin, or catecholamine analog to standard care vasopressors. The primary outcome was short-term mortality (at or before 28-30 days or intensive care discharge). Secondary outcomes included kidney replacement therapy, digital/peripheral ischemia, and venous thromboembolism. Random-effects meta-analyses were conducted to derive risk ratios (RRs) and 95% CIs. The certainty of the evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation. Results: Of 6,763 records, 17 trials (3,813 participants) were included. Compared with standard care, adjunctive vasopressor administration may reduce short-term mortality risk (RR, 0.92 [95% CI, 0.85-1.00], low certainty, 17 trials [3618 participants]) and likely reduces kidney replacement therapy receipt (RR, 0.92 [95% CI, 0.84-1.01], moderate certainty, eight trials [2,408 participants]). Adjunctive vasopressor treatment may increase risk of digital/peripheral ischemia (RR, 2.44 [95% CI, 1.17-5.10], low certainty, nine trials [2,981 participants]) and venous thromboembolism (RR, 16.48 [95% CI, 0.96-283.17], low certainty, one trial [321 participants]). There was some evidence that the pooled estimate for short-term mortality was different (interaction P = 0.13) for trials adjudicated as low risk of bias (RR, 0.95 [95% CI, 0.87-1.05]) compared with trials adjudicated as some concerns or high risk of bias (RR, 0.82 [95% CI, 0.69-0.97]). The findings were robust to multiple sensitivity and subgroup analyses. Conclusions: In adults with septic shock, adjunctive vasopressors may lower short-term death risk and likely lower kidney replacement therapy risk, but may increase risk of adverse effects. In the United States, adjunctive vasopressor use prevalence in septic shock is disconnected from the low evidence certainty for a favorable mortality-to-risk profile.
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Affiliation(s)
| | | | | | | | | | - Ryota Sato
- Division of Critical Care Medicine, The Queen's Medical Center, Honolulu, Hawaii
| | | | - Mary Schleicher
- The Cleveland Clinic Floyd D. Loop Alumni Library, Cleveland Clinic, Cleveland, Ohio
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12
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Tang Z, Zhu Y, Hu X, Lui K, Li S, Song X, Cai C, Guan X. Improving Intestinal Barrier Function in Sepsis by Partially Hydrolysed Guar Gum via the Suppression of the NF-κB/MLCK Pathway. Mol Biotechnol 2025; 67:2035-2045. [PMID: 38789715 DOI: 10.1007/s12033-024-01180-z] [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: 08/02/2023] [Accepted: 04/12/2024] [Indexed: 05/26/2024]
Abstract
Partially hydrolyzed guar gum (PHGG) protects against intestinal barrier dysfunction and can ameliorate some intestinal diseases. However, whether PHGG has a role in protecting intestinal barrier function (IBF) during sepsis remains unclear. This study aimed to investigate the role and probable mechanism of PHGG in the intestinal mucosa in sepsis. A rat sepsis model was constructed using cecal ligation and puncture (CLP). FITC-dextran 4 (FD-4) flux, serum inflammatory mediator levels, tight junction (TJ) levels, jejunum mucosa pathology, and epithelial intercellular junction ultrastructure were monitored to evaluate the effect of PHGG on IBF. Caco-2 monolayers were used to study the impact and mechanism of PHGG on lipopolysaccharide (LPS)-induced barrier dysfunction in vitro. The expression of zonula occludens protein-1 and occludin and the location of P65 were studied by immunofluorescence. Nuclear factor kappa B (NF-κB) and myosin light chain kinase 3 (MLCK) pathway-related protein expression was verified by quantitative reverse transcriptase polymerase chain reaction or western blotting. The results indicated that the jejunal mucosa structure was destroyed, the villi were disrupted and shortened, and neutrophil infiltration was evident in the septic rats. Compared to Sham group, spetic rats had increased Chiu's score, serum inflammatory mediator levels, and FD-4 flux but decreased TJ and gap junction density. In addition, the expression of MLCK, p-MLC, and TJ proteins and the expression of P65 in the nucleus were increased in septic rats. Furthermore, compared to those in the Control group, LPS-treated Caco-2 cells showed lower cell viability and transepithelial electrical resistance, while had higher FD-4 flux and the expression of MLCK, p-MLC, TJ proteins and P65 in the nucleus. PHGG pretreatment reversed the above effects induced by CLP or LPS treatment. Moreover, SN50, an NF-κB inhibitor, attenuated the above effects of LPS on Caco-2 cells. Overall, PHGG reduced inflammation, increased TJ protein expression and localization, and relieved damage to the TJ structure and intestinal permeability through suppression of the NF-κB/MLCK pathway. This study provides new insights into the role of PHGG in sepsis therapy.
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Affiliation(s)
- Zhaoxia Tang
- Department of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Er Road, Guangzhou, 510080, China
| | - Yanping Zhu
- Department of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Er Road, Guangzhou, 510080, China
| | - Xiaoguang Hu
- Department of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Er Road, Guangzhou, 510080, China
| | - Kayin Lui
- Department of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Er Road, Guangzhou, 510080, China
| | - Shuhe Li
- Department of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Er Road, Guangzhou, 510080, China
| | - Xiaodong Song
- Department of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Er Road, Guangzhou, 510080, China
| | - Changjie Cai
- Department of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Er Road, Guangzhou, 510080, China.
| | - Xiangdong Guan
- Department of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Er Road, Guangzhou, 510080, China.
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13
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Song YF, Huang HN, Ma JJ, Xing R, Song YQ, Li L, Zhou J, Ou CQ. Early prediction of sepsis in emergency department patients using various methods and scoring systems. Nurs Crit Care 2025; 30:e13201. [PMID: 39460424 DOI: 10.1111/nicc.13201] [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: 04/06/2024] [Revised: 09/30/2024] [Accepted: 10/13/2024] [Indexed: 10/28/2024]
Abstract
BACKGROUND Early recognition of sepsis, a common life-threatening condition in intensive care units (ICUs), is beneficial for improving patient outcomes. However, most sepsis prediction models were trained and assessed in the ICU, which might not apply to emergency department (ED) settings. AIM To establish an early predictive model based on basic but essential information collected upon ED presentation for the follow-up diagnosis of sepsis observed in the ICU. STUDY DESIGN This study developed and validated a reliable model of sepsis prediction among ED patients by comparing 10 different methods based on retrospective electronic health record data from the MIMIC-IV database. In-ICU sepsis was identified as the primary outcome. The potential predictors encompassed baseline demographics, vital signs, pain scale, chief complaints and Emergency Severity Index (ESI). 80% and 20% of the total of 425 737 ED visit records were randomly selected for the train set and the test set for model development and validation, respectively. RESULTS Among the methods evaluated, XGBoost demonstrated an optimal predictive performance with an area under the curve (AUC) of 0.90 (95% CI: 0.90-0.91). Logistic regression exhibited a comparable predictive ability to XGBoost, with an AUC of 0.89 (95% CI: 0.89-0.90), along with a sensitivity and specificity of 85% (95% CI: 0.83-0.86) and 78% (95% CI: 0.77-0.80), respectively. Neither of the five commonly used severity scoring systems demonstrated satisfactory performance for sepsis prediction. The predictive ability of using ESI as the sole predictor (AUC: 0.79, 95% CI: 0.78-0.80) was also inferior to the model integrating ESI and other basic information. CONCLUSIONS The use of ESI combined with basic clinical information upon ED presentation accurately predicted sepsis among ED patients, strengthening its application in ED. RELEVANCE TO CLINICAL PRACTICE The proposed model may assist nurses in risk stratification management and prioritize interventions for potential sepsis patients, even in low-resource settings.
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Affiliation(s)
- Yun-Feng Song
- The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China
| | - Hao-Neng Huang
- State Key Laboratory of Organ Failure Research, Department of Biostatistics, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China
| | - Jia-Jun Ma
- State Key Laboratory of Organ Failure Research, Department of Biostatistics, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China
| | - Rui Xing
- The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China
| | - Yu-Qi Song
- Department of Nursing, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou, China
| | - Li Li
- State Key Laboratory of Organ Failure Research, Department of Biostatistics, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China
| | - Jin Zhou
- Department of Nursing, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou, China
| | - Chun-Quan Ou
- State Key Laboratory of Organ Failure Research, Department of Biostatistics, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China
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Niu K, Wang Y, Pang Z, Niu M, Sun Z, Luo J, Xia C, Qian Y, Xu Z, Luo Y, Wu Y, Zhang D, Cao J. Development of a Multiplexed qPCR Kit for the Detection of Bloodstream Infection. J Clin Lab Anal 2025; 39:e70037. [PMID: 40260954 PMCID: PMC12089792 DOI: 10.1002/jcla.70037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 03/04/2025] [Accepted: 04/05/2025] [Indexed: 04/24/2025] Open
Abstract
BACKGROUND Bloodstream infection (BSI) is associated with high morbidity and mortality worldwide. Currently, BSI diagnosis relies on a time-consuming blood culture method, which usually takes 2 or more days to identify the causative pathogens. Cell-free DNA (cfDNA) refers to those small nucleic acid fragments residing in plasma and other body fluids, which have been used to detect cancer, organ transplantation injury, and pathogenic infections. A new multiplexed fluorescent quantitative PCR kit aiming at plasma microbial cfDNA was developed in this study. The kit contains multiple panels, and each panel covers multiple pathogens, including E. coli, K. pneumoniae, A. baumannii, H. influenzae, P. aeruginosa, E. faecalis, E. faecium, S. aureus, and S. epidermidis. METHODS PCR primers and probes were designed based on effective bacterial sequence segments, which were obtained from the analysis of next-generation sequencing results of plasma samples of patients with bloodstream infections. Bioinformatics analyses and experimental evidence were used to test the conservativeness and specificity of the primers and probes. The lower detection limit of the kit was determined under optimal reaction conditions. Clinical samples were used to test the accuracy of the kit's detection. RESULTS The lower detection limit of the kit has reached ≤ 12 copies per reaction. Clinical samples testing results showed a 90.48% consistency between the kit and blood culture. CONCLUSION The kit provides a rapid, accurate, and reliable method for diagnosing bloodstream infections. This can quickly provide an etiological basis for clinical diagnosis and further treatment, potentially improving patient outcomes.
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Affiliation(s)
- Kai Niu
- Center for Basic and Translational Research, the 2nd Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouChina
- Ningbo Health Gene Technologies co., ltd.NingboChina
| | - Yiping Wang
- The Clinical Laboratory Department of the Affiliated People's Hospital of Ningbo UniversityNingboChina
| | - Zhiyu Pang
- Ningbo Health Gene Technologies co., ltd.NingboChina
| | - Miaomiao Niu
- Ningbo Health Gene Technologies co., ltd.NingboChina
| | - Zhitong Sun
- Ningbo Health Gene Technologies co., ltd.NingboChina
| | - Jennie Luo
- The Clinical Laboratory Department of the Affiliated People's Hospital of Ningbo UniversityNingboChina
| | - Chaoqun Xia
- The Clinical Laboratory Department of the Affiliated People's Hospital of Ningbo UniversityNingboChina
| | - Yanqiao Qian
- Ningbo Health Gene Technologies co., ltd.NingboChina
| | - Zhi Xu
- Ningbo Health Gene Technologies co., ltd.NingboChina
| | - Yong Luo
- Ningbo Health Gene Technologies co., ltd.NingboChina
| | - Yong Wu
- Ningbo Health Gene Technologies co., ltd.NingboChina
| | - Dijun Zhang
- Ningbo Health Gene Technologies co., ltd.NingboChina
| | - Jiang Cao
- Center for Basic and Translational Research, the 2nd Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouChina
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15
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Yang H, Feng L, Jiang Z, Xiao Y, Zeng K. MONOCYTES AND B CELLS MEDIATE ALTERATIONS IN THE GENETIC ASSOCIATION BETWEEN PLATELETS AND SEPSIS VIA CLEC SIGNALING PATHWAY. Shock 2025; 63:714-722. [PMID: 39749956 DOI: 10.1097/shk.0000000000002547] [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: 01/04/2025]
Abstract
ABSTRACT Background: Sepsis is a life-threatening condition characterized by multiple organ dysfunction. Blood cells abnormalities play a significant role in the onset and progression of sepsis; however, the potential causal relationship between platelets and sepsis remains unclear, as does whether immune cells mediate the interaction between platelets and sepsis. This study aims to explore the potential causal relationship between platelets and sepsis and analyze the mediating effect of immune cells. In addition, cell-to-cell communication was analyzed to explore the interaction between blood cells and immune cells. Material and methods: In this study, genome-wide association study data were utilized to examine the association between blood cells and sepsis. Two-sample Mendelian randomization (MR) and reverse MR were performed to investigate the potential causal relationship between blood cells and sepsis, with a specific focus on the relationship between platelets and sepsis. Subsequently, two-step MR was employed to identify the immune cells that mediate the interaction between platelets and sepsis and to assess their potential mediating effects. Cellchat software was used to analyze cell-to-cell communication. Results: The results of two-sample MR indicated that platelets were negatively correlated with sepsis (OR = 0.976, 95% CI 0.959-0.993, P = 0.005), suggesting that platelets have a protective effect against sepsis. Additionally, reverse MR demonstrated that sepsis had no significant effect on platelets (OR = 0.909, 95% CI 0.156-5.296, P = 0.916). The mediating effect analysis revealed that monocytes and B cells were important mediators in the relationship between platelets and sepsis. Notably, the correlation between platelets and sepsis shifted from negative to positive with the involvement of monocytes and B cells. The number and strength of cell-cell interactions were decreased in sepsis. Monocytes and B cells primarily regulate platelets through the CLEC signaling pathway, contributing to the pathogenesis of sepsis. Conclusion: This study confirmed the protective role of platelets in sepsis. Monocytes and B cells mediate changes in the genetic association between platelets and sepsis. Monocytes and B cells primarily interact with platelets via the CLEC pathway, thereby modulating the genetic association between platelets and sepsis. These findings indicate that thrombocytopenia, especially when accompanied by elevated monocytes and B cells, may serve as a potential marker for sepsis.
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Affiliation(s)
- Hang Yang
- Department of Anesthesiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Lin Feng
- Department of Hematology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Zhenjie Jiang
- Department of Anesthesiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Yirong Xiao
- Department of Anesthesiology, 907 Hospital of the Joint Logistics Team, Nanping, China
| | - Kai Zeng
- Department of Anesthesiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
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Hird C, Parker M. Suspected sepsis: patient assessment and management in the emergency department. Emerg Nurse 2025; 33:34-41. [PMID: 39931742 DOI: 10.7748/en.2025.e2221] [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] [Accepted: 11/27/2024] [Indexed: 05/07/2025]
Abstract
Sepsis is a potentially life-threatening condition triggered by infection that is responsible for an estimated 48,000 deaths in the UK each year. Its pathophysiology is complex, its symptomology non-specific and its clinical presentations extremely varied. Despite numerous campaigns to raise awareness of sepsis, it still goes undetected. In 2024, the National Institute for Health and Clinical Excellence revised its guideline on sepsis and the UK Sepsis Trust published the seventh edition of its Sepsis Manual. This article discusses the pathophysiology of sepsis and how emergency nurses should assess and manage patients with suspected sepsis. It describes the tools available to them, including the National Early Warning Score 2 and the Sepsis 6, and emphasises the importance of early antibiotic administration, serial lactate measurements, source control and antimicrobial stewardship.
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Affiliation(s)
- Clare Hird
- Oxford University Hospitals NHS Trust, Oxford, England
| | - Mike Parker
- University of York, Department of Health Sciences, York, England
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17
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Liu L, Ma Q, Yu G, Ji X, He H. Association between the (neutrophil + monocyte)/albumin ratio and all-cause mortality in sepsis patients: a retrospective cohort study and predictive model establishment according to machine learning. BMC Infect Dis 2025; 25:579. [PMID: 40264028 PMCID: PMC12012944 DOI: 10.1186/s12879-025-10969-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Accepted: 04/14/2025] [Indexed: 04/24/2025] Open
Abstract
INTRODUCTION Sepsis is a life-threatening condition characterized by widespread inflammatory response syndrome in the body resulting from infection. Previous studies have demonstrated that some inflammatory factors or nutritional elements contributed to deaths in patients diagnosed with sepsis. Nevertheless, the correlation between the (neutrophil + monocyte)/albumin (NMa) ratio and all-cause mortality of patients diagnosed with sepsis remains unclear. This study aims to investigate the association between the NMa ratio and all-cause mortality in sepsis patients and to develop a predictive model using machine learning techniques. METHODS The clinical data were harvested from 13,851 patients with sepsis from the MIMIC-IV (3.1) database. We divided the subjects into four groups based on quartiles of the NMa ratio. The main endpoint was 30-day all-cause mortality, and the secondary endpoint was 90-day all-cause mortality. The relationship between the NMa ratio and adverse prognosis was investigated employing Cox proportional hazard regression, restricted cubic splines, and Kaplan‒Meier curves. Moreover, we employed Boruta algorithm to evaluate the predictive potential of the NMa ratio and established the prediction models utilizing machine learning algorithms. RESULTS After adjusting for confounders, each unit increase in the NMa ratio was associated with a 1.8% and 1.6% higher risk of 30-day and 90-day all-cause mortality, respectively (P < 0.001), indicating a linear relationship, and when treated as a categorical variable, the Quartile 4 group demonstrated a significantly higher mortality risk. Boruta feature selection also displayed that the NMa ratio possessed a higher Z score, and the models established utilizing the Cox and Random Forest algorithm identified excellent predictive performance (area under the curve (AUC) = 0.72, AUC = 0.74, respectively). CONCLUSION The NMa ratio is strongly and linearly associated with 30-day and 90-day all-cause mortality, with higher levels significantly increasing mortality risk, even after adjusting for potential confounders. Predictive models using Cox regression and Random Forest algorithms showed strong performance, indicating that the NMa ratio could function as a predictor of negative prognosis in patients with sepsis.
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Affiliation(s)
- Lulu Liu
- Cardiac Division of Emergency Intensive Care Unit, Beijing Anzhen Hospital, Capital Medical University, Anzhen Road Second, Chaoyang District, Beijing, 100029, People's Republic of China
| | - Qian Ma
- Cardiac Division of Emergency Intensive Care Unit, Beijing Anzhen Hospital, Capital Medical University, Anzhen Road Second, Chaoyang District, Beijing, 100029, People's Republic of China
| | - Guangzan Yu
- Cardiac Division of Emergency Intensive Care Unit, Beijing Anzhen Hospital, Capital Medical University, Anzhen Road Second, Chaoyang District, Beijing, 100029, People's Republic of China
| | - Xuhou Ji
- Cardiac Division of Emergency Intensive Care Unit, Beijing Anzhen Hospital, Capital Medical University, Anzhen Road Second, Chaoyang District, Beijing, 100029, People's Republic of China
| | - Hua He
- Cardiac Division of Emergency Intensive Care Unit, Beijing Anzhen Hospital, Capital Medical University, Anzhen Road Second, Chaoyang District, Beijing, 100029, People's Republic of China.
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Liu J, Hu J, Yao X, Xu M, Yuan A, Guo J, Wang C, Le Y, Yuan X, Lu D. CLICs Inhibitor IAA94 Alleviates Inflammation and Injury in Septic Liver by Preventing Pyroptosis in Macrophages. Inflammation 2025:10.1007/s10753-025-02304-6. [PMID: 40259192 DOI: 10.1007/s10753-025-02304-6] [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: 12/02/2024] [Revised: 03/18/2025] [Accepted: 04/14/2025] [Indexed: 04/23/2025]
Abstract
Macrophage pyroptosis represents a pivotal mechanism underlying acute liver injury during sepsis. Chloride intracellular channel proteins (CLICs) have been linked to inflammatory reflexes, with IAA94 serving as an inhibitor of channel formation characteristic of CLICs. In a mouse model, IAA94 demonstrated efficacy in reducing pro-inflammatory cytokines in liver tissues, decreasing macrophage in the liver, inhibiting the development of the pro-fibrosis phenotype, and alleviating tissue injury. Additionally, IAA94 exhibited inhibitory effects on the activation of NLRP3 inflammasome, leading to the suppression of pyroptosis in J774A.1 cells and the liver. Additionally, IAA94 was observed to impede the interaction between NEK7 and NLRP3. Furthermore, it was observed that the conditioned medium of pyroptotic macrophages treated with IAA94 induced an attenuated inflammatory response in hepatocytes in comparison to that induced by the conditioned medium of pyroptotic macrophages. However, NLRP3 overexpression impeded the beneficial effects of IAA94. In conclusion, IAA94 has the capacity to impede NLRP3 inflammasome formation-mediated pyroptosis by blocking CLICs-mediated chloride efflux and the inhibition of NEK7-NLRP3 interactions, thereby establishing CLICs as a promising therapeutic target against liver inflammation.
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Affiliation(s)
- Jing Liu
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China
- Lipid Metabolism Institute (Molecular Medicine Institute), Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Jingwen Hu
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China
- Lipid Metabolism Institute (Molecular Medicine Institute), Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Xulei Yao
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China
- Lipid Metabolism Institute (Molecular Medicine Institute), Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Mengting Xu
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China
- Lipid Metabolism Institute (Molecular Medicine Institute), Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Aini Yuan
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China
- Lipid Metabolism Institute (Molecular Medicine Institute), Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Jianan Guo
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China
- Lipid Metabolism Institute (Molecular Medicine Institute), Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Cui Wang
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China
- Lipid Metabolism Institute (Molecular Medicine Institute), Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Yifei Le
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China
- Lipid Metabolism Institute (Molecular Medicine Institute), Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Xingyu Yuan
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
- Lipid Metabolism Institute (Molecular Medicine Institute), Zhejiang Chinese Medical University, Hangzhou, 310053, China.
| | - Dezhao Lu
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
- Lipid Metabolism Institute (Molecular Medicine Institute), Zhejiang Chinese Medical University, Hangzhou, 310053, China.
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19
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Roye-Green KJ, Vickers I, Priestley S, Walker J, Willis R. Knowledge, practice and attitudes of healthcare students to sepsis management in Jamaica. BMC MEDICAL EDUCATION 2025; 25:565. [PMID: 40247330 PMCID: PMC12007360 DOI: 10.1186/s12909-025-07122-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Accepted: 04/05/2025] [Indexed: 04/19/2025]
Abstract
BACKGROUND Sepsis is a medical emergency requiring timely management and available global evidence suggests that healthcare workers and students are poorly prepared to effectively diagnose and treat such patients. This study evaluates the inter-relationship of healthcare students' attitudes towards, knowledge of and practice of sepsis management as they progress through training in Jamaica. METHODS A prospective cross-sectional survey using an anonymous self-administered questionnaire with convenience sampling was performed among healthcare students at all levels of training. All available medical and nursing students from the major public medical and nursing schools in the Kingston Metropolitan Area were included in the study. The questionnaire was composed of 25 items covering aspects of the knowledge, attitudes, and practice of sepsis management. RESULTS The study population consisted of 292 respondents; 210 medical and 82 nursing students. The need for fluid resuscitation before ICU admission (72.6%) was the practice question that was correctly identified by the majority of students. Most of the remaining items were correctly identified by approximately half of the students including signs of sepsis such as altered mental state (56.1%), low systolic blood pressure (53.7%) and tachypnea (50.6%). In contrast, very few students could identify the signs that indicated the presence of septic shock such as high serum lactate and the need for vasopressors and only 7% of students knew the correct annual sepsis mortality rate. Nursing students had higher overall mean correct knowledge and correct practice scores compared to medical students and lower incorrect practice scores, although there was no difference in incorrect knowledge scores between the 2 respondent groups. A subgroup analysis of students in their final stage of training revealed a more comparable performance of the 2 student groups, highlighting the improved performance by both nursing and medical students who received either formal sepsis training or were in the late stage of training. Jamaican healthcare students agree that more training on sepsis is needed (98.3%) and that sepsis care bundles should be implemented during their training courses (94.2%). CONCLUSIONS This study revealed differences in the healthcare students' attitudes, knowledge of and practice of sepsis in Jamaica. There is the need for training on sepsis and implementation of sepsis care bundles.
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Affiliation(s)
- Karen J Roye-Green
- Department of Microbiology, Faculty of Medical Sciences, University of the West Indies, Mona, Kingston, Jamaica.
| | - Ivan Vickers
- Department of Microbiology, Faculty of Medical Sciences, University of the West Indies, Mona, Kingston, Jamaica
| | - Sharon Priestley
- Department of Sociology, Psychology and Social Work, Faculty of Social Sciences, University of the West Indies,Mona, Kingston, Jamaica
| | - Jerome Walker
- Department of Microbiology, Faculty of Medical Sciences, University of the West Indies, Mona, Kingston, Jamaica
| | - Rohan Willis
- Medical Branch, Internal Medicine Rheumatology Division, University of Texas, Galveston, USA
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20
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Dos Santos BDN, Beruti C, Azevedo J, Herrando I, Vieira P, Domingos H, Heald R, Fernandez L, Parvaiz A. Using inflammatory parameters for safe and early discharge after minimally invasive colorectal surgery for colorectal cancer. Tech Coloproctol 2025; 29:97. [PMID: 40192855 PMCID: PMC11976749 DOI: 10.1007/s10151-025-03134-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Accepted: 02/23/2025] [Indexed: 04/10/2025]
Abstract
BACKGROUND Minimally invasive surgery has become the gold standard for colorectal cancer treatment. Approximately 40% of patients undergoing elective colorectal resection develop postoperative complications. The median time to clinical diagnosis of a postoperative complication ranges between 5 and 8 days. Early detection of complications can reduce their morbidity and negative impact. This study aims to evaluate the effectiveness of routine postoperative inflammatory markers in predicting early postoperative complications in patients undergoing elective minimally invasive surgery for colorectal cancer. METHODS This study was conducted at a single center and is a retrospective analysis of a prospectively mantained database. We included 397 consecutive patients who underwent elective minimally invasive surgery for colorectal cancer between May 2012 and September 2023. Routine inflammatory parameters, including C-reactive protein, Glasgow Prognostic Score, and neutrophil-lymphocyte ratio, were analyzed to identify those associated with postoperative complications. The cutoff values for these markers were determined using receiver-operating characteristic (ROC) curve analysis with the Youden index method. RESULTS Of the patients, 29.2% experienced postoperative complications, with major complications (Clavien-Dindo ≥ III) occurring in 11.3%. On postoperative day 3, C-reactive protein level < 125 mg/L, Glasgow Prognostic Score < 2.12, and neutrophil-lymphocyte ratio < 5.26 were significantly associated with lower risk of postoperative complications (p < 0.0001). NLR was the best parameter to identify patients unlikely to experience a postoperative complication on day 3, with a cutoff value of 5.26 and a negative predictive value (NPV) of 83%. CONCLUSIONS Neutrophil-lymphocyte ratio, C-reactive protein, and Glasgow Prognostic Score on POD3 can predict postoperative complications in patients who undergoing minimally invasive surgery for colorectal cancer. These inflammatory markers demonstrated high negative predictive value, effectively identifying patients who are unlikely to develop complications and providing valuable information for safe early discharge.
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Affiliation(s)
- B D N Dos Santos
- Digestive Unit, Champalimaud Foundation, Av Brasilia, 1400-038, Lisbon, Portugal
| | - C Beruti
- Hospital Universitario Austral, Buenos Aires, Argentina
| | - J Azevedo
- Digestive Unit, Champalimaud Foundation, Av Brasilia, 1400-038, Lisbon, Portugal
- Faculty of Medicine, University of Lisbon, Lisbon, Portugal
| | - I Herrando
- Digestive Unit, Champalimaud Foundation, Av Brasilia, 1400-038, Lisbon, Portugal
| | - P Vieira
- Digestive Unit, Champalimaud Foundation, Av Brasilia, 1400-038, Lisbon, Portugal
| | - H Domingos
- Digestive Unit, Champalimaud Foundation, Av Brasilia, 1400-038, Lisbon, Portugal
| | - R Heald
- Digestive Unit, Champalimaud Foundation, Av Brasilia, 1400-038, Lisbon, Portugal
| | - L Fernandez
- Digestive Unit, Champalimaud Foundation, Av Brasilia, 1400-038, Lisbon, Portugal.
| | - A Parvaiz
- Digestive Unit, Champalimaud Foundation, Av Brasilia, 1400-038, Lisbon, Portugal
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21
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Scheer CS, Giamarellos-Bourboulis EJ, Ferrer R, Idelevich EA, Annane D, Artigas A, Aslan AT, Bottari G, Bouma HR, Černý V, Curić Radivojević R, Dakou K, Dewitte K, Elbahnasawy M, Gründling M, Gurjar M, Hästbacka J, Kyprianou M, Laribi S, Lassen A, Lebedinskii K, Máca J, Malbrain MLNG, Monti G, Ostermann M, Osthoff M, Paiva JA, Sabbatucci M, Śmiechowicz J, Ştefan MG, Vollmer M, Vuković N, Zaragkoulias K, Reinhart K, Linder A, Filipescu D. Status of Sepsis Care in European Hospitals: Results from an International Cross-Sectional Survey. Am J Respir Crit Care Med 2025; 211:587-599. [PMID: 39787606 PMCID: PMC12005017 DOI: 10.1164/rccm.202406-1167oc] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Accepted: 01/06/2025] [Indexed: 01/12/2025] Open
Abstract
Rationale: Early detection, standardized therapy, adequate infrastructure, and strategies for quality improvement should constitute essential components of every hospital's sepsis plan. Objectives: To investigate the extent to which recommendations from the sepsis guidelines are implemented and the availability of infrastructure for the care of patients with sepsis in acute-care hospitals. Methods: A multidisciplinary cross-sectional questionnaire was used to investigate sepsis care in hospitals. This included the use of sepsis definitions, the implementation of sepsis guideline recommendations, diagnostic and therapeutic infrastructure, antibiotic stewardship, and quality improvement initiatives (QIIs) in hospitals. Measurements and Main Results: A total of 1,023 hospitals in 69 countries were included. Most of them, 835 (81.6%), were in Europe. Sepsis screening was used in 54.2% of emergency departments (EDs), 47.9% of wards, and 61.7% of ICUs. Sepsis management was standardized in 57.3% of EDs, 45.2% of wards, and 70.7% of ICUs. The implementation of comprehensive QIIs was associated with increased screening (EDs, +33.3%; wards, +44.4%; ICUs, +23.8% absolute difference) and increased standardized sepsis management (EDs, +33.6%; wards, +40.0%; ICUs, +17.7% absolute difference) compared with hospitals without QIIs. A total of 9.8% of hospitals had implemented ongoing QIIs, and 4.6% had invested in sepsis programs. Conclusions: The findings indicate that there is considerable room for improvement in a large number of mainly European hospitals, particularly with regard to early identification and standardized management of sepsis, the availability of guidelines, diagnostic and therapeutic infrastructure, and the implementation of QIIs. Further efforts are required to implement a more comprehensive and appropriate quality of care.
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Affiliation(s)
- Christian S. Scheer
- Department of Anesthesiology, Intensive Care Medicine, Emergency Medicine and Pain Medicine, University Medicine Greifswald, Greifswald, Germany
| | | | - Ricard Ferrer
- Intensive Care Department, Vall d’Hebron University Hospital. SODIR Research Group, Vall d’Hebron Research Institute. Medicine Department, Autonomous University of Barcelona, Barcelona, Spain
| | - Evgeny A. Idelevich
- Friedrich Loeffler Institute of Medical Microbiology, University Medicine Greifswald, Greifswald, Germany
- Institute of Medical Microbiology, University Hospital Münster, Münster, Germany
| | - Djillali Annane
- Service de Réanimation, Hôpital Raymond Poincaré, Assistance Publique—Hôpitaux de Paris, Garches, France
- Université Versailles Saint-Quentin, Versailles, France
| | - Antonio Artigas
- Sabadell University Hospital, Research and Innovation Institute Parc Tauli (I3PT CERCA), CIBER Respiratory Diseases, Autonomous University of Barcelona, Sabadell, Spain
| | | | - Gabriella Bottari
- Pediatric Intensive Care Unit Children Hospital Bambino Gesú, Institute for Health and Research, Rome, Italy
| | - Hjalmar R. Bouma
- Department of Internal Medicine, Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Vladimir Černý
- Department of Anesthesia and Intensive Care Medicine, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic
- Faculty of Social Sciences and Health Care, Constantine the Philosopher University in Nitra, Nitra, Slovakia
| | - Renata Curić Radivojević
- Department of Anesthesiology, Resuscitation and Intensive Care, Zagreb University Hospital Centre, Zagreb, Croatia
| | | | - Ken Dewitte
- Emergency Department, Antwerp University Hospital, Antwerp, Belgium
| | - Mohamed Elbahnasawy
- Department of Emergency Medicine and Traumatology, Tanta University, Tanta, Egypt
| | - Matthias Gründling
- Department of Anesthesiology, Intensive Care Medicine, Emergency Medicine and Pain Medicine, University Medicine Greifswald, Greifswald, Germany
| | - Mohan Gurjar
- Department of Critical Care Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Johanna Hästbacka
- Department of Perioperative, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Department of Anesthesia and Intensive Care, Tampere University Hospital, Wellbeing Services County of Pirkanmaa and Tampere University, Tampere, Finland
| | - Miltiadis Kyprianou
- Fourth Department of Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece
| | - Said Laribi
- Emergency Medicine Department, Tours University, School of Medicine and Tours University Hospital, Centre Hospitalier Universitaire de Tours, Tours, France
| | - Annmarie Lassen
- Department of Emergency Medicine, Odense University Hospital, Odense, Denmark
| | - Konstantin Lebedinskii
- Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, North-West State Medical University named after I.I. Mechnikov, St. Petersburg, Russia
| | - Jan Máca
- Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine, University Hospital Ostrava and University of Ostrava, Ostrava, Czech Republic
| | - Manu L. N. G. Malbrain
- First Department of Anesthesiology and Intensive Therapy, Medical University of Lublin, Lublin, Poland
- Medical Data Management, Medaman, Geel, Belgium
| | - Gianpaola Monti
- Anestesia e Rianimazione dei Trapianti Dipartimento Chirurgico Polispecialistico ASST, Grande Ospedale Metropolitano Niguarda Milano, Milan, Italy
| | - Marlies Ostermann
- Department of Critical Care, King’s College London, Guy’s and St. Thomas’ Hospital, London, United Kingdom
| | - Michael Osthoff
- Division of Internal Medicine, University Hospital Basel, Basel, Switzerland
- Departments of Biomedicine and Clinical Research, University of Basel, Basel, Switzerland
| | - José-Artur Paiva
- Intensive Care Medicine Service, Sao Joao Local Health Unit, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Michela Sabbatucci
- Department of Infectious Diseases, Italian National Institute of Health, Rome, Italy
| | - Jakub Śmiechowicz
- Clinical Department of Anesthesiology and Intensive Therapy, Wroclaw Medical University, Wroclaw, Poland
| | - Mihai Gabriel Ştefan
- Department of Anesthesiology and Intensive Care, “Prof. Dr. CC Iliescu” Emergency Institute for Cardiovascular Diseases, Bucharest, Romania
| | - Marcus Vollmer
- Institute of Bioinformatics, University Medicine Greifswald, Greifswald, Germany
| | - Natalija Vuković
- Clinic for Anesthesiology, Reanimation and Intensive Care, University Clinical Center Niš, Nis, Serbia
| | - Kyriakos Zaragkoulias
- Department of Laboratory Medicine, Section for Medical Microbiology, Nord-Trøndelag Hospital Trust, Levanger, Norway
- Department of Medical Microbiology, St. Olav’s Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Konrad Reinhart
- Department of Anesthesiology and Operative Intensive Care Medicine, Charité University Medicine Berlin, Berlin, Germany
| | - Adam Linder
- Division of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, Sweden; and
| | - Daniela Filipescu
- Department of Anesthesiology and Intensive Care, “Prof. Dr. CC Iliescu” Emergency Institute for Cardiovascular Diseases, Bucharest, Romania
- University of Medicine and Pharmacy Carol Davila, Bucharest, Romania
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Fuller H, Tittanegro TH, Maini AA, China L, Rhodes F, Becares Salles N, Mukhopadhyay S, Moore B, O’Brien A. Hyperbilirubinemia at hospitalization predicts nosocomial infection in decompensated cirrhosis: Data from ATTIRE trial. Hepatol Commun 2025; 9:e0648. [PMID: 40126412 PMCID: PMC11927652 DOI: 10.1097/hc9.0000000000000648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Accepted: 10/11/2024] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND To identify clinical characteristics and serological biomarkers that predicted subsequent nosocomial infection in ATTIRE trial patients. METHODS We identified 360 patients at hospitalization without infection and not prescribed antibiotics and compared clinical characteristics between those who subsequently developed a nosocomial infection and not. In a 68-patient subcohort, we compared plasma biomarkers of bacterial translocation, infection, and inflammation at hospitalization between those who developed a nosocomial infection and not. In a 56-patient subcohort, we investigated plasma lipidomic profiles in those who did and did not develop nosocomial infection using Lipotype Shotgun platform analysis and multivariate statistical techniques. To further investigate lipid pathways, we compared outcomes in patients taking statins or not at hospitalization. RESULTS Serum bilirubin >188 µmol/L at hospitalization predicted subsequent nosocomial infection in univariate and multivariate analyses, with 80% specificity. The most common nosocomial infections were respiratory tract (29%) and those developing infection had significantly greater 28 and 90-day mortality than those not (p=9.34E-05 and 0.014). Serological biomarkers of bacterial translocation, infection, and inflammation did not predict subsequent infection. Partial least squares discriminatory analyses identified cholesterol esters (CEs) (CE.18.1.2, CE.18.1.0, and CE.16.0.0) as important predictors of infection but provided only a small improvement in predictive ability over bilirubin alone. RNA-sequencing analyses suggest this is mediated by a downregulation of the cellular cholesterol esterification enzyme sterol O-acyltransferase 1. Statin use was not associated with nosocomial infection prevention. CONCLUSIONS In ATTIRE, elevated serum bilirubin at hospitalization was the only clinical characteristic that predicted subsequent development of nosocomial infection. Considering the rising incidence of antimicrobial resistance, these data could be used to limit antibiotic prophylaxis or aid trial design for investigating use in high-risk patients.
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Affiliation(s)
- Harriett Fuller
- School of Food Science and Nutrition, University of Leeds, Leeds, UK
| | - Thais H. Tittanegro
- Division of Medicine, UCL Institute for Liver and Digestive Health, London, UK
| | - Alexander A. Maini
- Division of Medicine, UCL Institute for Liver and Digestive Health, London, UK
| | - Louise China
- Division of Medicine, UCL Institute for Liver and Digestive Health, London, UK
| | - Freya Rhodes
- Division of Medicine, UCL Institute for Liver and Digestive Health, London, UK
| | | | - Subhankar Mukhopadhyay
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London Strand London, UK
| | - Bernadette Moore
- School of Food Science and Nutrition, University of Leeds, Leeds, UK
| | - Alastair O’Brien
- Division of Medicine, UCL Institute for Liver and Digestive Health, London, UK
- Comprehensive Clinical Trials Unit, University College London, UK
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23
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Rosa MDSD, Rech G, Goulart Rosa R, Mezzomo Pasqual H, Teixeira C. Treatment Intensity and Outcomes in Elderly Mechanically Ventilated ICU Patients. Respir Care 2025; 70:434-439. [PMID: 39348942 DOI: 10.4187/respcare.12317] [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: 06/26/2024] [Accepted: 09/20/2024] [Indexed: 10/02/2024]
Abstract
Background: The global population is aging, and the proportion of elderly patients admitted to ICUs is increasing. In this scenario, achieving a balance between judicious utilization of a limited and high-cost resource and providing optimal intensity of care presents a challenge given that in very elderly patients the value of ICU care is uncertain. The aim of our study was to evaluate the survival of older subjects admitted to ICU who require mechanical ventilation at different levels of treatment intensity. Methods: A comprehensive longitudinal ICU database was retrospectively analyzed at a single tertiary center, from January 2008-December 2014, of ICU subjects 80 y old or older who required mechanical ventilation. Results: From January 2009-December 2014, 482 subjects were admitted to the ICU and required mechanical ventilation. Among them, 376 (78%) were age 80-89 y; and 106 (22%) were age ≥ 90 y, with a mean age of 85.84 (4.56). The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 21.53 (7.42), and the mean Sequential Organ Failure Assessment score was 5.75 (3.38). The total mortality during ICU admission was 46%, and the hospital mortality was 58%. Only age higher than 90 y (1.41 [1.05-1.91], P = .02) and APACHE score (1.03 [1.01-1.05], P < .001) were associated with mortality after adjustments. The Therapeutic Intervention Scoring System score was analyzed in tertiles and was not related to mortality in univariate analysis or after adjustments. Conclusions: Our data indicate that in older subjects who received mechanical ventilation higher intensity of treatment does not seem to translate into a survival benefit. This finding highlights the importance of considering individualized treatment plans for elderly patients in the ICU.
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Affiliation(s)
| | - Gabriela Rech
- The authors are affiliated with Hospital Moinhos de Vento, Porto Alegre, Rio Grande do Sul, Brazil
| | - Regis Goulart Rosa
- The authors are affiliated with Hospital Moinhos de Vento, Porto Alegre, Rio Grande do Sul, Brazil
| | - Henrique Mezzomo Pasqual
- The authors are affiliated with Hospital Moinhos de Vento, Porto Alegre, Rio Grande do Sul, Brazil
| | - Cassiano Teixeira
- The authors are affiliated with Hospital Moinhos de Vento, Porto Alegre, Rio Grande do Sul, Brazil
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Gu X, Yang P, Yu L, Yuan J, Zhang Y, Yuan Z, Chen L, Zhang X, Chen Q. Glucocorticoids can reduce mortality in patients with severe community-acquired pneumonia: a systematic review and meta-analysis of randomized controlled trials. Eur J Med Res 2025; 30:215. [PMID: 40148914 PMCID: PMC11951802 DOI: 10.1186/s40001-025-02487-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Accepted: 03/20/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND Severe community-acquired pneumonia (sCAP) is associated with higher morbidity and mortality. The use of glucocorticoids to improve the prognosis of severe community-acquired pneumonia remains a topic of controversy. METHODS Following the guidelines given in the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA), we conducted a systematic review and meta-analysis to evaluate the effects of glucocorticoids on mortality and duration of mechanical ventilation in patients with sCAP. Randomized controlled studies investigating the use of glucocorticoids in the treatment of sCAP were extracted from PubMed, Embase, Cochrane Library, and Web of Science. Statistical analysis was performed to compare the differences in in-hospital mortality, mechanical ventilation duration, gastrointestinal bleeding, secondary infection, and other outcome measures between the glucocorticoid group and the control group. RESULTS A total of 8 studies involving 1769 patients were included in the analysis. The hospital mortality in the glucocorticoid group was significantly lower than that in the control group [8 studies, relative risk (RR) 0.59; 95% CI 0.47-0.76, p < 0.01. I2 = 25%, low certainty]. The duration of mechanical ventilation in the glucocorticoid group was significantly shorter than that in the control group [Mean Difference (MD) -3.08; 95% CI -4.96 to -1.19, p < 0.01; I2 = 0%, low certainty]. There was no significant difference in the incidence of gastrointestinal bleeding (RR 0.94; 95% CI 0.55-1.63, p = 0.84, I2 = 0%, low certainty) or secondary infection (RR 0.85; 95% CI 0.58-1.25, p = 0.85, I2 = 2%, moderate certainty) between the glucocorticoid group and the control group. In subgroup analysis, mortality was significantly lower in the hydrocortisone group compared to the control group (6.3% vs. 14.6%, RR 0.43; 95% CI 0.29-0.62, p < 0.01, I2 = 0%, very low certainty). However, there was no significant difference in mortality between the methylprednisolone group and the control group (15.6% vs. 19.9%, RR 0.78; 95% CI 0.57-1.08, p = 0.14, I2 = 0%, moderate certainty). CONCLUSION Glucocorticoids can reduce mortality in patients with sCAP, and the effect may vary depending on the type and the dose of glucocorticoids used. Additionally, glucocorticoid treatment can lead to a shorter duration of mechanical ventilation, as well as the length of ICU stay, without increasing the risk of gastrointestinal bleeding or secondary infection in patients with sCAP. PROSPERO registration: CRD42023416525.
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Affiliation(s)
- Xue Gu
- Department of Critical Care Medicine, Jiangdu People'S Hospital Affiliated to Yangzhou University, Yangzhou, 225200, Jiangsu, China
| | - Penglei Yang
- Department of Critical Care Medicine, Jiangdu People'S Hospital Affiliated to Yangzhou University, Yangzhou, 225200, Jiangsu, China
| | - Lina Yu
- Department of Critical Care Medicine, Jiangdu People'S Hospital Affiliated to Yangzhou University, Yangzhou, 225200, Jiangsu, China
| | - Jun Yuan
- Department of Critical Care Medicine, Jiangdu People'S Hospital Affiliated to Yangzhou University, Yangzhou, 225200, Jiangsu, China
| | - Ying Zhang
- Department of Critical Care Medicine, Jiangdu People'S Hospital Affiliated to Yangzhou University, Yangzhou, 225200, Jiangsu, China
| | - Zhou Yuan
- Department of Critical Care Medicine, Jiangdu People'S Hospital Affiliated to Yangzhou University, Yangzhou, 225200, Jiangsu, China
| | - Lianxin Chen
- Department of Critical Care Medicine, Jiangdu People'S Hospital Affiliated to Yangzhou University, Yangzhou, 225200, Jiangsu, China
| | - Xiaoli Zhang
- Department of Critical Care Medicine, Jiangdu People'S Hospital Affiliated to Yangzhou University, Yangzhou, 225200, Jiangsu, China
| | - Qihong Chen
- Department of Critical Care Medicine, Jiangdu People'S Hospital Affiliated to Yangzhou University, Yangzhou, 225200, Jiangsu, China.
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China.
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Heffernan A, Ganguli R, Sears I, Stephen AH, Heffernan DS. Choice of Machine Learning Models Is Important to Predict Post-Operative Infections in Surgical Patients. Surg Infect (Larchmt) 2025. [PMID: 40107772 DOI: 10.1089/sur.2024.288] [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: 03/22/2025] Open
Abstract
Background: Surgical quality datasets are critical to decision-making tools including surgical infection (SI). Machine learning models (MLMs), a branch of artificial intelligence (AI), are increasingly being ingrained within surgical decision-making algorithms. However, given the unique and distinct functioning of individual models, not all models may be suitable for acutely ill surgical patients. Patients and Methods: This is a 5-year retrospective review of National Surgical Quality Improvement Program (NSQIP) patients who underwent an operation. The data were reviewed for demographics, medical comorbidities, rates, and sites of infection. To generate the MLMs, data were imported into Python, and four common MLMs, extreme gradient boosting, K-nearest neighbor (KNN), random forest, and logistic regression, as well as two novel models (flexible discriminant analysis and generalized additive model) and ensemble modeling, were generated to predict post-operative SIs. Outputs included area under the receiver-operating characteristic curve (AUC ROC) including recall curves. Results: Overall, 624,625 urgent and emergent NSQIP patients were included. The overall infection rate was 8.6%. Patients who sustained a post-operative infection were older, more likely geriatric, male, diabetic, had chronic obstructive pulmonary disease, were smokers, and were less likely White race. With respect to MLMs, all four MLMs had reasonable accuracy. However, a hierarchy of MLMs was noted with predictive abilities (XGB AUC = 0.85 and logistic regression = 0.82), wherein KNN has the lowest performance (AUC = 0.62). With respect to the ability to detect an infection, precision recall of XGB performed well (AUC = 0.73), whereas KNN performed poorly (AUC = 0.16). Conclusions: MLMs are not created nor function similarly. We identified differences with MLMs to predict post-operative infections in surgical patients. Before MLMs are incorporated into surgical decision making, it is critical that surgeons are at the fore of understanding the role and functioning of MLMs.
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Affiliation(s)
- Addison Heffernan
- Division of Trauma and Surgical Critical Care, Department of Surgery, Warren Alpert School of Medicine, Brown University, Providence, Rhode Island, USA
| | - Reetam Ganguli
- Division of Trauma and Surgical Critical Care, Department of Surgery, Warren Alpert School of Medicine, Brown University, Providence, Rhode Island, USA
| | - Isaac Sears
- Division of Trauma and Surgical Critical Care, Department of Surgery, Warren Alpert School of Medicine, Brown University, Providence, Rhode Island, USA
| | - Andrew H Stephen
- Division of Trauma and Surgical Critical Care, Department of Surgery, Warren Alpert School of Medicine, Brown University, Providence, Rhode Island, USA
| | - Daithi S Heffernan
- Division of Trauma and Surgical Critical Care, Department of Surgery, Warren Alpert School of Medicine, Brown University, Providence, Rhode Island, USA
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Guo J, He X, Bai Y, Sun H, Yang J. Virulence factors of Salmonella Typhi: interplay between the bacteria and host macrophages. Arch Microbiol 2025; 207:89. [PMID: 40095029 DOI: 10.1007/s00203-025-04297-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 02/20/2025] [Accepted: 03/05/2025] [Indexed: 03/19/2025]
Abstract
Salmonella Typhi (S. Typhi) is a Gram-negative bacterium that exclusively infects humans and causes typhoid fever- a major global public health concern responsible for approximately 9 million infections and 110,000 deaths annually. Macrophages, a key component of the innate immune system, play essential roles in pathogen clearance, antigen presentation, immune regulation, and tissue repair. As one of the primary targets of S. Typhi infection, macrophages significantly influence disease onset and progression. S. Typhi expresses a range of virulence factors, including the virulence-associated (Vi) capsule, outer membrane proteins (OMPs), flagella, fimbriae, type III secretion systems (T3SSs) and other genes encoded on Salmonella pathogenicity islands (SPIs), as well as toxins, regulatory factors, and virulence plasmids. These virulence factors facilitate S. Typhi's intracellular survival within macrophages by mediating processes such as adhesion, invasion, nutrient acquisition and immune evasion, ultimately enabling systemic infection. This review explores the role and molecular mechanisms of S. Typhi virulence factors in counteracting macrophage antimicrobial functions, providing insights for future research on typhoid pathogenesis and the development of potential therapeutic interventions.
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Affiliation(s)
- Jiayin Guo
- Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University, Cuiying Gate 82, Lanzhou, Gansu, 730030, China
| | - Xiaoe He
- Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University, Cuiying Gate 82, Lanzhou, Gansu, 730030, China
| | - Yanrui Bai
- Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University, Cuiying Gate 82, Lanzhou, Gansu, 730030, China
| | - Hui Sun
- Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University, Cuiying Gate 82, Lanzhou, Gansu, 730030, China
| | - Jing Yang
- Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University, Cuiying Gate 82, Lanzhou, Gansu, 730030, China.
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Yang L, Xuan R, Xu D, Sang A, Zhang J, Zhang Y, Ye X, Li X. Comprehensive integration of diagnostic biomarker analysis and immune cell infiltration features in sepsis via machine learning and bioinformatics techniques. Front Immunol 2025; 16:1526174. [PMID: 40129981 PMCID: PMC11931141 DOI: 10.3389/fimmu.2025.1526174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Accepted: 02/14/2025] [Indexed: 03/26/2025] Open
Abstract
Introduction Sepsis, a critical medical condition resulting from an irregular immune response to infection, leads to life-threatening organ dysfunction. Despite medical advancements, the critical need for research into dependable diagnostic markers and precise therapeutic targets. Methods We screened out five gene expression datasets (GSE69063, GSE236713, GSE28750, GSE65682 and GSE137340) from the Gene Expression Omnibus. First, we merged the first two datasets. We then identified differentially expressed genes (DEGs), which were subjected to KEGG and GO enrichment analyses. Following this, we integrated the DEGs with the genes from key modules as determined by Weighted Gene Co-expression Network Analysis (WGCNA), identifying 262 overlapping genes. 12 core genes were subsequently selected using three machine-learning algorithms: random forest (RF), Least Absolute Shrinkage and Selection Operator (LASSO), and Support Vector Machine-Recursive Feature Elimination (SVW-RFE). The utilization of the receiver operating characteristic curve in conjunction with the nomogram model served to authenticate the discriminatory strength and efficacy of the key genes. CIBERSORT was utilized to evaluate the inflammatory and immunological condition of sepsis. Astragalus, Salvia, and Safflower are the primary elements of Xuebijing, commonly used in the clinical treatment of sepsis. Using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), we identified the chemical constituents of these three herbs and their target genes. Results We found that CD40LG is not only one of the 12 core genes we identified, but also a common target of the active components quercetin, luteolin, and apigenin in these herbs. We extracted the common chemical structure of these active ingredients -flavonoids. Through docking analysis, we further validated the interaction between flavonoids and CD40LG. Lastly, blood samples were collected from healthy individuals and sepsis patients, with and without the administration of Xuebijing, for the extraction of peripheral blood mononuclear cells (PBMCs). By qPCR and WB analysis. We observed significant differences in the expression of CD40LG across the three groups. In this study, we pinpointed candidate hub genes for sepsis and constructed a nomogram for its diagnosis. Discussion This research not only provides potential diagnostic evidence for peripheral blood diagnosis of sepsis but also offers insights into the pathogenesis and disease progression of sepsis.
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Affiliation(s)
- Liuqing Yang
- Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
- Department of Anesthesiology, Hubei Provincial Engineering Research Center of Minimally Invasive Cardiovascular Sugery, Wuhan, China
- Department of Anesthesiology, Wuhan Clinical Research Center for Minimally Invasive Treatment of Structural Heart Disease, Wuhan, China
| | - Rui Xuan
- Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
- Department of Anesthesiology, Hubei Provincial Engineering Research Center of Minimally Invasive Cardiovascular Sugery, Wuhan, China
- Department of Anesthesiology, Wuhan Clinical Research Center for Minimally Invasive Treatment of Structural Heart Disease, Wuhan, China
| | - Dawei Xu
- Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
- Department of Anesthesiology, Hubei Provincial Engineering Research Center of Minimally Invasive Cardiovascular Sugery, Wuhan, China
- Department of Anesthesiology, Wuhan Clinical Research Center for Minimally Invasive Treatment of Structural Heart Disease, Wuhan, China
| | - Aming Sang
- Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
- Department of Anesthesiology, Hubei Provincial Engineering Research Center of Minimally Invasive Cardiovascular Sugery, Wuhan, China
- Department of Anesthesiology, Wuhan Clinical Research Center for Minimally Invasive Treatment of Structural Heart Disease, Wuhan, China
| | - Jing Zhang
- Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
- Department of Anesthesiology, Hubei Provincial Engineering Research Center of Minimally Invasive Cardiovascular Sugery, Wuhan, China
- Department of Anesthesiology, Wuhan Clinical Research Center for Minimally Invasive Treatment of Structural Heart Disease, Wuhan, China
| | - Yanfang Zhang
- Department of Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Xujun Ye
- Department of Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Xinyi Li
- Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
- Department of Anesthesiology, Hubei Provincial Engineering Research Center of Minimally Invasive Cardiovascular Sugery, Wuhan, China
- Department of Anesthesiology, Wuhan Clinical Research Center for Minimally Invasive Treatment of Structural Heart Disease, Wuhan, China
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Zhou D, He L, Shi W, Ma P. Lessons from the similarities and differences in fluid resuscitation between burns and sepsis: a bibliometric analysis. Front Med (Lausanne) 2025; 12:1561619. [PMID: 40103790 PMCID: PMC11914137 DOI: 10.3389/fmed.2025.1561619] [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: 01/16/2025] [Accepted: 02/13/2025] [Indexed: 03/20/2025] Open
Abstract
Background Fluid is an essential component of initial resuscitation in sepsis or burns. Meanwhile, the optimal strategy of titrating fluids for both of the two conditions remains uncertain. In this bibliometric analysis, we compared the similarities and differences in fluid resuscitation between sepsis and burns in recent publications. Methods Literatures related to fluid resuscitation in either sepsis or burns were searched in the Web of Science database Core Collection from January 1, 1992, to December 31, 2022. CiteSpace and VOSviewer was used for bibliometric analysis. Results A total of 1,549 and 468 publications on fluid resuscitation in sepsis and burns were retrieved from 1992 to 2022. Based on the occurrences, 341 and 86 high-frequency keywords were screened out from sepsis and burns publications, respectively, which were similarly categorized into 5 clusters [i.e. "mechanisms of hypovolemia" (cluster 1), "titration of fluid" (cluster 2), "outcomes or complications" (cluster 3), "pathophysiological alternations" (cluster 4), and "fluid types and others" (cluster 5)]. The high-frequency keywords of the top 20 were more concentrated in cluster 3 and cluster 2, with "mortality" ranked the top in both sepsis and burns literature. Significantly, 3 keywords in cluster 2 ranked in the top 5, including "goal directed resuscitation" (the 3rd), fluid responsiveness (the 4th) and fluid balance (the 5th) in sepsis literature, while the keywords of "microvascular exchange" (cluster 1) and "abdominal compartment syndrome" (ACS, cluster 3) ranked at the second and the fifth place in burns publications. Keyword burst analysis demonstrated that the keyword with the highest burst strength (BS) was "formula" (BS = 5.88, 2008-2014), followed by management (BS = 4.79, 2012-2022), ACS (BS = 4.76, 2006-2010), and fluid creep (BS = 4.74, 2011-2016) in burn publications, but they were dobutamine (BS = 12.31, 1992-2008), cardiac output (BS = 9.79, 1993-2001), catecholamine (BS = 9.54, 1993-2006), and consumption (BS = 7.52, 1992-2006) in sepsis literature. Moreover, the most frequently cited article in either sepsis or burns was categorized into cluster 2, that investigated goal-directed fluid therapy for sepsis and formula improvement for burns resuscitation. Conclusion It was demonstrated that the research priorities in titrating fluid were mainly concentrated on targeting hemodynamics in sepsis vs. improving formula (which briefly calculates the increased microvascular permeability) in burns, while concerning of "outcomes and complications" in fluid resuscitation similarly after 1992. However, hemodynamics and microvascular permeability have been simultaneously well considered in few previous studies regarding fluid resuscitation in either sepsis or burns.
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Affiliation(s)
- Dongxu Zhou
- Department of Critical Care Medicine, Guiqian International General Hospital, Guiyang, China
| | - LuLu He
- Department of Critical Care Medicine, Guiqian International General Hospital, Guiyang, China
| | - Wei Shi
- Department of Critical Care Medicine, Guiqian International General Hospital, Guiyang, China
| | - Penglin Ma
- Department of Critical Care Medicine, Guiqian International General Hospital, Guiyang, China
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Zhan JH, Wei J, Liu YJ, Wang PX, Zhu XY. Sepsis-associated endothelial glycocalyx damage: a review of animal models, clinical evidence, and molecular mechanisms. Int J Biol Macromol 2025; 295:139548. [PMID: 39788232 DOI: 10.1016/j.ijbiomac.2025.139548] [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: 07/03/2024] [Revised: 12/21/2024] [Accepted: 01/05/2025] [Indexed: 01/12/2025]
Abstract
In the mammalian cardiovascular system, endothelial glycocalyx is a gel-like layer that covers the luminal surface of endothelial cells (ECs) and plays crucial roles in vascular homeostasis, permeability and leukocyte adhesion. Degradation of this structure occurs early in sepsis and becomes accordingly dysfunctional. In severe cases, it is not self-regulated by the organism. However, the relationship between the glycocalyx and the occurrence and development of sepsis remains poorly understood. One possibility is that thinned glycocalyx promotes leukocyte recognition and adhesion, thereby facilitating the elimination of pathogens from infected areas. This may represent a protective mechanism developed by the organism during through evolutionary processes. However, if the damage persists and disrupts the dynamic balance of the microcirculation, interstitial edema or organ failure can occur. Thus, we asked the questions, what is the precise composition and structure of the glycocalyx? How is it degraded? What animal models are available to study the relationship between the glycocalyx and sepsis? What glycocalyx biomarkers are found in the blood of patients with sepsis? To determine whether sepsis can be treated by interfering with the glycocalyx, this study provides a systematic summary and discussion of the latest progress in addressing these questions.
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Affiliation(s)
- Jun-Hui Zhan
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China; Department of Physiology, Naval Medical University, Shanghai 200433, China
| | - Juan Wei
- School of Sports and Health, Nanjing Sport Institute, Nanjing 210014, China
| | - Yu-Jian Liu
- School of Kinesiology, The Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China
| | - Peng-Xiang Wang
- Department of Physiology, Naval Medical University, Shanghai 200433, China.
| | - Xiao-Yan Zhu
- Department of Physiology, Naval Medical University, Shanghai 200433, China.
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Lexnoi T, Boonpeng A, Santimaleeworagun W, Chaisiri K, Dechsanga J, Vattanavanit V, Ungthammakhun C, Sitaruno S. The Effects of the Early and Late Phases of Septic Shock on the Population Pharmacokinetics of Vancomycin. J Clin Pharmacol 2025. [PMID: 39967294 DOI: 10.1002/jcph.70009] [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: 10/31/2024] [Accepted: 02/06/2025] [Indexed: 02/20/2025]
Abstract
Pathophysiologic changes in the early and late phases of septic shock affect the pharmacokinetic (PK) parameters, varying dose adjustments may be necessary. This study aimed to create the PK models of vancomycin in the early and late phases of septic shock and to describe the association between the area under the curve from 0 to 24 h (AUC0-24) and acute kidney injury (AKI). The data from patients with septic shock receiving vancomycin was collected either prospectively or retrospectively. A nonlinear mixed-effects modeling approach was used to develop the PK models. A total of 208 septic shock patients were enrolled and classified into the early (n = 96) and the late phase (n = 112). A two-compartment PK model is the best base model for both phases of septic shock. The model that best predicted the clearance (CL) of both phases was the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation, which was not indexed to body surface area (BSA). Albumin (ALB) was a covariate associated with vancomycin CL only in the late phase. The typical values of CL and volume of distribution (Vd) in the early phase were 1.71 L/h and 68.94 L. In the late phase, CL was 1.65 L/h, and Vd was 66.36 L. The AKI was observed in patients with a high simulated AUC0-24. The population PK model of vancomycin in the early and late phases of septic shock has been established. The CKD-EPI not indexed to BSA predicts vancomycin CL in both phases. ALB was associated with CL in the late phase.
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Affiliation(s)
- Tanisa Lexnoi
- Division of Clinical Pharmacy, Department of Pharmacy, Chonburi Hospital, Muang, Chonburi, Thailand
| | - Apinya Boonpeng
- School of Pharmaceutical Sciences, University of Phayao, Muang, Phayao, Thailand
| | | | - Kessarin Chaisiri
- Division of Clinical Pharmacy, Department of Pharmacy, Chonburi Hospital, Muang, Chonburi, Thailand
| | - Jutamas Dechsanga
- Division of Pulmonary and Critical Care, Department of Medicine, Chonburi Hospital, Muang, Chonburi, Thailand
| | - Veerapong Vattanavanit
- Division of Critical Care Medicine, Department of Internal Medicine, Faculty of Medicine, Prince of Songkhla University, Hat Yai, Songkhla, Thailand
| | - Chutchawan Ungthammakhun
- Division of Infectious Disease, Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailand
| | - Sirima Sitaruno
- Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, Thailand
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Ma J, Wang X, Zhang Y, Ge C. Effect of liberal glucose control on critically ill patients: a systematic review and meta-analysis. BMC Endocr Disord 2025; 25:36. [PMID: 39934786 PMCID: PMC11817051 DOI: 10.1186/s12902-025-01864-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 02/04/2025] [Indexed: 02/13/2025] Open
Abstract
BACKGROUND Most current guideline statements support some level of unrestricted glycemic management in critically ill adult patients. Nevertheless, the effectiveness of liberal glucose control is currently not well-supported by evidence. Therefore, our objective is to investigate the influence of liberal glucose control (> 180 mg/dl) on critically ill patients in the intensive care unit (ICU). METHODS Until November 23, 2023, English language literature was thoroughly and systematically searched through multiple databases, including PubMed, Embase, Cochrane Library, and Web of Science. Our primary endpoints of interest were the occurrence of hypoglycemia, mortality in the ICU, and mortality during hospitalization. In addition, our secondary outcomes comprised of 90-day mortality, bloodstream infections, the proportion of patients necessitating renal replacement therapy (RRT), the length of time under mechanical ventilation, duration of stay in the ICU, and length of the overall hospitalization. Weighted mean difference (WMD) and relative risk (RR) were respectively computed as overall effect size for continuous and dichotomous data and reported with their 95% confidence intervals (95% CI). RESULTS A total of 9 studies were incorporated, which included 14,878 patients in the ICU. Compared with other blood glucose target control groups, liberal glucose control significantly reduced the incidence of hypoglycemia (RR = 0.41; 95% CI:0.25 to 0.69; P = 0.001), but increased ICU mortality (RR = 1.23; 95% CI:1.03 to 1.48; P = 0.023), in-hospital mortality risk (RR = 1.18; 95% CI:1.03 to 1.35; P = 0.020), and the risk of requiring RRT (RR = 1.26; 95% CI:1.11 to1.42; P < 0.001). CONCLUSION Liberal glucose control can reduce the risk of hypoglycemia but increases the risks of ICU mortality, in-hospital mortality, and the requirement for RRT. To confirm the outcomes further, large-scale, high-quality clinical trials are necessary.
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Affiliation(s)
- Jiahui Ma
- Second District of Critical Care Medicine, Hai 'an People's Hospital, Nantong City, Jiangsu Province, 226600, China
| | - Xu Wang
- Department of Nursing, Hai 'an People's Hospital, Nantong, Jiangsu, 226600, China
| | - Yan Zhang
- Second District of Critical Care Medicine, Hai 'an People's Hospital, Nantong City, Jiangsu Province, 226600, China
| | - Chunyan Ge
- Department of Nursing, Hai 'an People's Hospital, Nantong, Jiangsu, 226600, China.
- Haian People's Hospital, 17 Zhongba Middle Road, Haian City, Nantong City, Jiangsu Province, 226600, China.
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Ferreira JC, Vianna AODA, Pinheiro BV, Maia IS, Baldisserotto SV, Isola AM. Joint statement on evidence-based practices in mechanical ventilation: suggestions from two Brazilian medical societies. J Bras Pneumol 2025; 51:e20240255. [PMID: 39936726 PMCID: PMC11796564 DOI: 10.36416/1806-3756/e20240255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 09/04/2024] [Indexed: 02/13/2025] Open
Abstract
Mechanical ventilation can be a life-saving intervention, but its implementation requires a multidisciplinary approach, with an understanding of its indications and contraindications due to the potential for complications. The management of mechanical ventilation should be part of the curricula during clinical training; however, trainees and practicing professionals frequently report low confidence in managing mechanical ventilation, often seeking additional sources of knowledge. Review articles, consensus statements and clinical practice guidelines have become important sources of guidance in mechanical ventilation, and although clinical practice guidelines offer rigorously developed recommendations, they take a long time to develop and can address only a limited number of clinical questions. The Associação de Medicina Intensiva Brasileira and the Sociedade Brasileira de Pneumologia e Tisiologia sponsored the development of a joint statement addressing all aspects of mechanical ventilation, which was divided into 38 topics. Seventy-five experts from all regions of Brazil worked in pairs to perform scoping reviews, searching for publications on their specific topic of mechanical ventilation in the last 20 years in the highest impact factor journals in the areas of intensive care, pulmonology, and anesthesiology. Each pair produced suggestions and considerations on their topics, which were presented to the entire group in a plenary session for modification when necessary and approval. The result was a comprehensive document encompassing all aspects of mechanical ventilation to provide guidance at the bedside. In this article, we report the methodology used to produce the document and highlight the most important suggestions and considerations of the document, which has been made available to the public in Portuguese.
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Affiliation(s)
- Juliana Carvalho Ferreira
- . Division of Pulmonology, Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo - São Paulo (SP), Brazil
| | | | - Bruno Valle Pinheiro
- . Hospital Universitário, Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Juiz de Fora - Juiz de Fora (MG), Brazil
| | - Israel Silva Maia
- . Department of Internal Medicine, Universidade Federal de Santa Catarina - Florianópolis (SC), Brazil
- . Hospital Nereu Ramos - Florianópolis (SC), Brazil
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Ouedraogo R, Alves A, Bruant A, Sy O, Tabra Osorio C, Schortgen F, Chenal A, Contou D, Krzyzaniak L, Fartoukh M, Le Joncour M, Mongardon N, Ait Benaissa L, Da Silva D, Bouguerra M, Demeret S, Tanguy Dubois S, Starczala E, Petyt C, Schmidt M, Dezellus S, Georger JF, Pallud AC, Carras D, Boussely F, Audureau E, Mekontso Dessap A. Infrared illumination for difficult peripheral venous catheterisation in critically ill adult patients: the prospective, randomised, multicentre ICARE trial. BMJ Open 2025; 15:e090611. [PMID: 39915026 PMCID: PMC11800220 DOI: 10.1136/bmjopen-2024-090611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Accepted: 01/26/2025] [Indexed: 02/09/2025] Open
Abstract
INTRODUCTION The insertion of a peripheral venous line is of paramount importance in the stabilisation of critically ill patients. It is a preferred method of venous access over more invasive techniques due to its immediacy and fewer complications. Difficulties of catheterisation can result in delays to treatment, increased complication risks and pain, and a waste of valuable time and healthcare resources. Our hypothesis is that infrared vein illumination could improve the success rate of peripheral venous catheterisation in critically ill patients at risk of difficult catheterisation. METHODS AND ANALYSIS This is a prospective, multicentre, randomised, open-label controlled trial. It will be conducted in France and will involve critically ill patients at risk of difficult peripheral catheterisation. Patients will be randomly assigned to usual care or infrared vein illumination. The primary outcome is the rate of successful peripheral venous catheterisation at first puncture. Secondary outcomes include time to placement, overall rate of successful peripheral venous catheterisation, number of punctures, quality (calibre of the catheter), replacement rate, need for central line and local complications (dysfunction, diffusion, haematoma and lymphangitis). ETHICS AND DISSEMINATION The study has been granted ethical approval (CPP Ile de France 1). Following the provision of informed consent, patients will be included in the study. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER NCT03932214.
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Affiliation(s)
- Rachida Ouedraogo
- Service de Médecine Intensive Réanimation, Hôpitaux Universitaires Henri Mondor, AP-HP, Créteil, France
- Groupe de Recherche Clinique CARMAS, Institut Mondor de recherche biomédicale, UPEC, Creteil, Île-de-France, France
| | - Aline Alves
- Service de Médecine Intensive Réanimation, Hôpitaux Universitaires Henri Mondor, AP-HP, Créteil, France
- Groupe de Recherche Clinique CARMAS, Institut Mondor de recherche biomédicale, UPEC, Creteil, Île-de-France, France
| | - Amélie Bruant
- Service de Médecine Intensive Réanimation, Groupe Hospitalier Sud Ile de France, Melun, France
| | - Oumar Sy
- Service de Médecine Intensive Réanimation, Groupe Hospitalier Sud Ile de France, Melun, France
| | - Cécilia Tabra Osorio
- Service de Médecine Intensive Réanimation Adulte, Centre Hospitalier Intercommunal de Créteil, Creteil, France
| | - Frédérique Schortgen
- Service de Médecine Intensive Réanimation Adulte, Centre Hospitalier Intercommunal de Créteil, Creteil, France
| | - Amélie Chenal
- Service de Réanimation Polyvalente, Centre Hospitalier Victor Dupouy, Argenteuil, France
| | - Damien Contou
- Service de Réanimation Polyvalente, Centre Hospitalier Victor Dupouy, Argenteuil, France
| | - Laurence Krzyzaniak
- Service de Médecine Intensive Réanimation, Département Médico-Universitaire APPROCHES, Hôpital Tenon, AP-HP, Sorbonne Université, Paris, France
| | - Muriel Fartoukh
- Service de Médecine Intensive Réanimation, Département Médico-Universitaire APPROCHES, Hôpital Tenon, AP-HP, Sorbonne Université, Paris, France
| | - Marianne Le Joncour
- Service d'Anesthésie-Réanimation, Hôpitaux Universitaires Henri Mondor, AP-HP, Paris, France
| | - Nicolas Mongardon
- Service d'Anesthésie-Réanimation, Hôpitaux Universitaires Henri Mondor, AP-HP, Paris, France
| | - Latifa Ait Benaissa
- Service de Médecine Intensive Réanimation, Centre Hospitalier de Saint-Denis, Hôpital Delafontaine, Saint Denis, Île-de-France, France
| | - Daniel Da Silva
- Service de Médecine Intensive Réanimation, Centre Hospitalier de Saint-Denis, Hôpital Delafontaine, Saint Denis, Île-de-France, France
| | - Meriem Bouguerra
- Neurological Intensive Care Medicine, La Pitie-Salpetriere Hospital, AP-HP, Paris, France
| | - Sophie Demeret
- Neurological Intensive Care Medicine, La Pitie-Salpetriere Hospital, AP-HP, Paris, France
| | | | - Eric Starczala
- Service de Médecine Intensive Réanimation, Centre Hospitalier Léon Binet, Provins, France
| | - Chirine Petyt
- Service de Médecine Intensive Réanimation, Hôpital Pitié-Salpêtrière, AP-HP, Sorbonne Université, Paris, France
| | - Matthieu Schmidt
- Service de Médecine Intensive Réanimation, Hôpital Pitié-Salpêtrière, AP-HP, Sorbonne Université, Paris, France
| | - Séverine Dezellus
- Service de Médecine Intensive Réanimation, Centre Hospitalier Intercommunal de Villeneuve Saint Georges, Villeneuve Saint Georges, France
| | - Jean Francois Georger
- Service de Médecine Intensive Réanimation, Centre Hospitalier Intercommunal de Villeneuve Saint Georges, Villeneuve Saint Georges, France
| | - Ann-Cécile Pallud
- Service de Médecine Intensive Réanimation, Hôpitaux Universitaires Henri Mondor, AP-HP, Créteil, France
- Groupe de Recherche Clinique CARMAS, Institut Mondor de recherche biomédicale, UPEC, Creteil, Île-de-France, France
| | - Damien Carras
- Service de Médecine Intensive Réanimation, Hôpitaux Universitaires Henri Mondor, AP-HP, Créteil, France
- Groupe de Recherche Clinique CARMAS, Institut Mondor de recherche biomédicale, UPEC, Creteil, Île-de-France, France
| | | | - Etienne Audureau
- Unité de Recherche Clinique Henri Mondor, Hôpitaux Universitaires Henri Mondor-Albert, AP-HP, CEPIA EA7376, Institut Mondor de Recherche Biomédicale, INSERM U955, Universite Paris-Est Creteil Val de Marne, Creteil, France
| | - Armand Mekontso Dessap
- Service de Médecine Intensive Réanimation, Hôpitaux Universitaires Henri Mondor, AP-HP, Créteil, France
- Groupe de Recherche Clinique CARMAS, Institut Mondor de recherche biomédicale, UPEC, Creteil, Île-de-France, France
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Hong S, Wang H, Fan X, Liu J, Qiao L. Effect of the hour-1 bundle on clinical outcomes in patients with sepsis and septic shock: A protocol for systematic review and meta-analysis. PLoS One 2025; 20:e0318914. [PMID: 39913424 PMCID: PMC11801614 DOI: 10.1371/journal.pone.0318914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 01/23/2025] [Indexed: 02/09/2025] Open
Abstract
BACKGROUND According to the 2018 bundle guidelines of the Surviving Sepsis Campaign, many emergency departments and intensive care units currently adopt the hour-1 bundle as a standard practice for sepsis management. However, recent studies on the hour-1 bundle for sepsis treatment have yielded inconsistent results, raising questions and challenges about its clinical efficacy. AIM This study will conduct a systematic review and meta-analysis to compare the impact of the hour-1 bundle and non-hour-1 bundle on the clinical outcomes in patients with sepsis and septic shock. METHODS The protocol was prepared according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses protocol (PRISMA-P) statement. The systematic review will be carried out in line with the statement of PRISMA. The following electronic databases will be searched: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science. All clinical studies comparing the impact of the hour-1 bundle and non-hour-1 bundle on clinical outcomes in patients with sepsis and septic shock will be included. All stages of the literature search, study selection, data extraction, and quality assessment will be conducted independently by two reviewers. Any disagreements between the two reviewers will be resolved by discussion or arbitration by a third reviewer. The primary outcome will be short-term mortality, which involves in-hospital, 28-day, 30-day, and 90-day mortality corresponding to the definition used in each study. For quality assessment, the risk of bias specified by the Cochrane Collaboration and the methodological index for non-randomized studies will be used for randomized control trials (RCTs) and non-RCTs, respectively. Data synthesis will be performed via Review Manager 5.1.0. EXPECTED RESULTS This systematic review will integrate all relevant studies to quantitatively estimate the effect size and clarify the role of the hour-1 bundle in sepsis management, contributing new evidence-based guidance to the field. SYSTEMATIC REVIEW REGISTRATION Protocol registration and reporting: PROSPERO CRD42024579314.
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Affiliation(s)
- Shukun Hong
- Department of Intensive Care Unit, Shengli Oilfield Central Hospital, Dongying, China
- Clinical Research Center of Dongying Critical Care Medicine, Dongying, China
| | - Hongye Wang
- Department of Obstetrics and Gynecology, Shengli Oilfield Central Hospital, Dongying, China
| | - Xiaoguang Fan
- Department of Intensive Care Unit, Shengli Oilfield Central Hospital, Dongying, China
- Clinical Research Center of Dongying Critical Care Medicine, Dongying, China
| | - Jian Liu
- Department of Intensive Care Unit, Shengli Oilfield Central Hospital, Dongying, China
- Clinical Research Center of Dongying Critical Care Medicine, Dongying, China
| | - Lujun Qiao
- Department of Intensive Care Unit, Shengli Oilfield Central Hospital, Dongying, China
- Clinical Research Center of Dongying Critical Care Medicine, Dongying, China
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Ferreira JC, Vianna AODA, Pinheiro BV, Maia IS, Baldisserotto SV, Isola AM. Joint statement on evidence-based practices in mechanical ventilation: suggestions from two Brazilian medical societies. CRITICAL CARE SCIENCE 2025; 37:e20250242en. [PMID: 39907364 PMCID: PMC11805462 DOI: 10.62675/2965-2774.20250242-en] [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: 07/30/2024] [Accepted: 10/03/2024] [Indexed: 02/06/2025]
Abstract
Mechanical ventilation can be a life-saving intervention, but its implementation requires a multidisciplinary approach, with an understanding of its indications and contraindications due to the potential for complications. The management of mechanical ventilation should be part of the curricula during clinical training; however, trainees and practicing professionals frequently report low confidence in managing mechanical ventilation, often seeking additional sources of knowledge. Review articles, consensus statements and clinical practice guidelines have become important sources of guidance in mechanical ventilation, and although clinical practice guidelines offer rigorously developed recommendations, they take a long time to develop and can address only a limited number of clinical questions. The Associação de Medicina Intensiva Brasileira and the Sociedade Brasileira de Pneumologia e Tisiologia sponsored the development of a joint statement addressing all aspects of mechanical ventilation, which was divided into 38 topics. Seventy-five experts from all regions of Brazil worked in pairs to perform scoping reviews, searching for publications on their specific topic of mechanical ventilation in the last 20 years in the highest impact factor journals in the areas of intensive care, pulmonology, and anesthesiology. Each pair produced suggestions and considerations on their topics, which were presented to the entire group in a plenary session for modification when necessary and approval. The result was a comprehensive document encompassing all aspects of mechanical ventilation to provide guidance at the bedside. In this article, we report the methodology used to produce the document and highlight the most important suggestions and considerations of the document, which has been made available to the public in Portuguese.
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Affiliation(s)
- Juliana Carvalho Ferreira
- Hospital das ClínicasFaculdade de MedicinaUniversidade de São PauloSão PauloSPBrazilDivision of Pulmonology, Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo - São Paulo (SP), Brazil.
| | | | - Bruno Valle Pinheiro
- Department of Internal MedicineFaculdade de MedicinaUniversidade Federal de Juiz de ForaJuiz de ForaMGBrazilHospital Universitário, Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Juiz de Fora - Juiz de Fora (MG),Brazil.
| | - Israel Silva Maia
- Department of Internal MedicineUniversidade Federal de Santa CatarinaFlorianópolisSCBrazilDepartment of Internal Medicine, Universidade Federal de Santa Catarina - Florianópolis (SC),Brazil.
- Hospital Nereu RamosFlorianópolisSCBrazilHospital Nereu Ramos - Florianópolis (SC), Brazil.
| | - Sérgio Vasconcellos Baldisserotto
- Santa Casa de Misericórdia de Porto AlegrePorto AlegreRSBrazilSanta Casa de Misericórdia de Porto Alegre - Porto Alegre (RS), Brazil.
| | - Alexandre Marini Isola
- Department of Continuing EducationImed GroupSão PauloSPBrazilDepartment of Continuing Education, Imed Group - São Paulo (SP), Brazil
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Yin M, Wang T, Jiang Q, Qu X, Ma J, Xu J, Jin X, Chen X. The association of red blood cell transfusion with mortality in pediatric patients with sepsis, severe sepsis, and septic shock: A single-center retrospective cohort study. Transfus Clin Biol 2025; 32:62-68. [PMID: 39710203 DOI: 10.1016/j.tracli.2024.12.002] [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: 10/29/2024] [Revised: 12/15/2024] [Accepted: 12/17/2024] [Indexed: 12/24/2024]
Abstract
BACKGROUND/OBJECTIVES Pediatric patients with sepsis are frequently subjected to red blood cell (RBC) transfusions but yet its association with mortality is still controversial. METHODS We consecutively selected 125 patients with sepsis, severe sepsis, and septic shock admitted to intensive care unit (ICU) in our center from January 2022 to January 2023, and finally 100 patients were included in this retrospective cohort study. The patients were divided into two groups: group I who received RBC transfusion and group II who did not receive RBC transfusion. Logistic regression analysis was used to determine the demographic and clinical factors related to receiving RBC transfusion. The association of RBC transfusion with mortality was determined by the Cox regression model, and the mechanical ventilation rate and length of stay by the logistic regression model. RESULTS Among the 100 patients, 67 and 33 cases belonged to the RBC-transfused and not-transfused groups, respectively. Lower hemoglobin level (OR = 0.918, 95%CI: 0.881-0.957, p < 0.001), increased c-reactive protein level (OR = 1.022, 95%CI: 1.002-1.043, p = 0.034), and lower platelets count (OR = 0.994, 95%CI: 0.988-0.999, p = 0.023) were associated with RBC transfusions. While the associations of RBC transfusion with mortality and mechanical ventilation were not shown to be statistically significant (HR = 3.926, 95%CI: 0.952-16.186, p = 0.058 and OR = 2.588, 95%CI: 0.832-8.046, p = 0.1), RBC transfusion might be associated with increased ICU length of stay (OR = 16.477, 95%CI: 3.86-70.342, p < 0.001). In the overall survival analysis, younger age (HR = 0.093, 95%CI: 0.027-0.320, p < 0.001), the use of mechanical ventilation (HR = 8.893, 95%CI: 1.483-53.336, p = 0.017), and more severe disease (severe sepsis vs. sepsis, HR = 24.531, 95%CI: 1.923-321.914, p = 0.014; septic shock vs. sepsis, HR = 32.187, 95%CI: 2.977-347.949, p = 0.004) were related to increased mortality. CONCLUSIONS RBC transfusions are significantly associated with increased ICU length of stay and not associated with 28-day mortality and mechanical ventilation rate. Other factors affecting mortality in pediatric patients with sepsis, severe sepsis, and septic shock are younger age, use of mechanical ventilation, and more severe disease.
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Affiliation(s)
- Mingwei Yin
- Department of Blood Transfusion, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang Province, PR China
| | - Ting Wang
- Department of Blood Transfusion, Tai'an Traditional Chinese Medicine Hospital, Tai'an, Shandong Province, PR China
| | - Qian Jiang
- Department of Blood Transfusion, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang Province, PR China
| | - Xinli Qu
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, PR China
| | - Jihua Ma
- Department of Blood Transfusion, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang Province, PR China
| | - Jun Xu
- Department of Blood Transfusion, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang Province, PR China
| | - Xiaobo Jin
- Department of Blood Transfusion, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang Province, PR China
| | - Xuejun Chen
- Department of Blood Transfusion, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang Province, PR China.
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Bowyer L, Cutts BA, Barrett HL, Bein K, Crozier TM, Gehlert J, Giles ML, Hocking J, Lowe S, Lust K, Makris A, Morton MR, Pidgeon T, Said J, Tanner HL, Wilkinson L, Wong M. SOMANZ position statement for the investigation and management of sepsis in pregnancy 2023. Aust N Z J Obstet Gynaecol 2025; 65:37-46. [PMID: 38922822 DOI: 10.1111/ajo.13848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Accepted: 05/19/2024] [Indexed: 06/28/2024]
Abstract
BACKGROUND The Society of Australia and New Zealand (SOMANZ) published its first sepsis in pregnancy and the postpartum period guideline in 2017 (Aust N Z J Obstet Gynaecol, 57, 2017, 540). In the intervening 6 years, maternal mortality from sepsis has remained static. AIMS To update clinical practice with a review of the subsequent literature. In particular, to review the definition and screening tools for the diagnosis of sepsis. MATERIALS AND METHODS A multi-disciplinary group of clinicians with experience in all aspects of the care of pregnant women analysed the clinical evidence according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system following searches of Cochrane, Medline and EMBASE. Where there were conflicting views, the authors reviewed the topic and came to a consensus. All authors reviewed the final position statement. RESULTS This position statement has abandoned the use of the quick Sequential Organ Failure Assessment score (qSOFA) score to diagnose sepsis due to its poor performance in clinical practice. Whilst New Zealand has a national maternity observation chart, in Australia maternity early warning system charts and vital sign cut-offs differ between states. Rapid recognition, early antimicrobials and involvement of senior staff remain essential factors to improving outcomes. CONCLUSION Ongoing research is required to discover and validate tools to recognize and diagnose sepsis in pregnancy. Australia should follow New Zealand and have a single national maternity early warning system observation chart.
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Affiliation(s)
- Lucy Bowyer
- Department of Obstetrics, Royal Hospital for Women, Sydney, New South Wales, Australia
| | - Briony A Cutts
- Department of Obstetric Medicine, Joan Kirner Women's and Children's at Sunshine Hospital, Melbourne, Victoria, Australia
| | - Helen L Barrett
- Department of Obstetric Medicine, Royal Hospital for Women, Sydney, New South Wales, Australia
| | - Kendall Bein
- Emergency Department, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
| | - Timothy M Crozier
- Department of Intensive Care, Monash Health, Department of Intensive Care Services, Eastern Health, Melbourne, Victoria, Australia
| | - Jessica Gehlert
- Department of Obstetrics and Gynaecology, Flinders Medical Centre, Adelaide, South Australia, Australia
| | - Michelle L Giles
- Department of Obstetrics and Gynaecology, Department of Infectious Diseases, Monash University, Melbourne, Victoria, Australia
| | - Jennifer Hocking
- Australian Breastfeeding Association, Melbourne, Victoria, Australia
| | - Sandra Lowe
- Department of Obstetric Medicine, Royal Hospital for Women, Sydney, New South Wales, Australia
| | - Karin Lust
- Department of Obstetric Medicine, Women's and Newborn Services, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
| | - Angela Makris
- Department of Nephrology, Liverpool Hospital, Sydney, New South Wales, Australia
| | - Mark R Morton
- Women's and Babies Division, Women's and Children's Hospital, Adelaide, South Australia, Australia
| | - Tara Pidgeon
- Emergency Department, St Vincent's Private Hospital, Toowoomba, Queensland, Australia
| | - Joanne Said
- Department of Maternal Fetal Medicine, Joan Kirner Women's and Children's at Sunshine Hospital, Melbourne, Victoria, Australia
| | - Helen L Tanner
- Department of Obstetric Medicine, Women's and Newborn Services, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
| | - Lucille Wilkinson
- Department of Medicine, Northland District Health Board, Auckland, New Zealand
| | - Maggie Wong
- Department of Anaesthesia, Royal Women's Hospital, Melbourne, Victoria, Australia
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Yun TG, Park JH, Kim HS, Shin MH, Kang MJ, Park MS, Pyun JC. Sepsis Diagnosis Based on a Parylene Matrix Chip Using LPC16:0 as a Biomarker in Comparison with Colorimetry of Total Phospholipid. ACS APPLIED BIO MATERIALS 2025; 8:609-616. [PMID: 39743741 DOI: 10.1021/acsabm.4c01453] [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: 01/04/2025]
Abstract
For the medical diagnosis of sepsis, it is crucial to differentiate infectious inflammation from noninfectious symptoms to prevent acute aggravation. Herein, a diagnosis for early stage sepsis was performed using LPC 16:0 and total phospholipids as small molecular biomarkers. The measurement of LPC 16:0 was conducted using a parylene matrix chip, which was developed to effectively detect small molecules in laser desorption/ionization mass spectrometry (LDI-MS). Meanwhile, the total phospholipid level was measured using colorimetry, following an enzymatic assay. Next, the two biomarkers were analyzed in serum samples from healthy volunteers, systemic inflammatory response syndrome (SIRS) patients, and sepsis patients. Diagnostic criteria were established based on the biomarker intensities observed in each patient group. After the measurements were conducted, the interference in phospholipid analysis due to hemoglobin contamination was considered. Additionally, the analytical parameters from biomarker detection were statistically interpreted and compared with those of conventional diagnostic standards. Finally, the diagnostic performance of each biomarker was evaluated by analyzing the biomarker levels between patient groups and examining their overlapping extents in box plots to distinguish sepsis from noninfectious inflammatory symptoms.
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Affiliation(s)
- Tae Gyeong Yun
- Department of Materials Science and Engineering, Yonsei University, 50 Yonsei-Ro, Seodaemun-Gu, Seoul 03722, South Korea
| | - Jun-Hee Park
- Department of Materials Science and Engineering, Yonsei University, 50 Yonsei-Ro, Seodaemun-Gu, Seoul 03722, South Korea
| | - Hye Soo Kim
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, South Korea
| | - Mi Hwa Shin
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, South Korea
- Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul 03722, South Korea
| | - Min-Jung Kang
- Korea Institute of Science and Technology (KIST), Seoul 02792, South Korea
| | - Moo Suk Park
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, South Korea
| | - Jae-Chul Pyun
- Department of Materials Science and Engineering, Yonsei University, 50 Yonsei-Ro, Seodaemun-Gu, Seoul 03722, South Korea
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Xu T, Song S, Zhu K, Yang Y, Wu C, Wang N, Lu S. Systemic inflammatory response index improves prognostic predictive value in intensive care unit patients with sepsis. Sci Rep 2025; 15:1908. [PMID: 39809872 PMCID: PMC11732978 DOI: 10.1038/s41598-024-81860-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Accepted: 11/29/2024] [Indexed: 01/16/2025] Open
Abstract
Sepsis is a severe infectious disease with high mortality. However, the indicators used to evaluate its severity and prognosis are relatively complicated. The systemic inflammatory response index (SIRI), a new inflammatory indicator, has shown good predictive value in chronic infection, stroke, and cancer. The purpose of this study was to investigate the connection between sepsis and SIRI and evaluate its predictive usefulness. A total of 401 patients with sepsis were included in this study. Multiple linear regression and logistic regression analyses were performed to evaluate the relationship between SIRI and sepsis. The restricted cubic spline (RCS) method was employed to illustrate the dose-response relationship. The area under the curve (AUC) and decision curve analysis (DCA) were used to evaluate the prognostic value of SIRI. Multiple linear regression analysis revealed a significant positive correlation between SIRI and both blood cell count and Sequential Organ Failure Assessment (SOFA) score. Additionally, higher SIRI levels were significantly linked to a higher risk of sepsis worsening, according to logistic regression analysis. The RCS curve demonstrated that the risk of poor prognosis rose with increasing SIRI, particularly when SIRI exceeded 6.1. Furthermore, AUC and DCA results showed that SIRI had superior predictive value compared to traditional indicators. A higher SIRI is linked to a worse prognosis and more severe sepsis. SIRI may serve as a novel prognostic indicator in sepsis, though further clinical studies are necessary to confirm these findings.
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Affiliation(s)
- Tuo Xu
- Xinxiang Central Hospital, Xinxiang, Henan, People's Republic of China
- The Fourth Clinical College of Xinxiang Medical University, Xinxiang, Henan, People's Republic of China
- Nantong University Hospital, Nantong, Jiangsu, People's Republic of China
| | - Shuaiwei Song
- Graduate School, Xinjiang Medical University, Urumqi, Xinjiang, People's Republic of China
| | - Ke Zhu
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
| | - Yin Yang
- The Fourth Clinical College of Xinxiang Medical University, Xinxiang, Henan, People's Republic of China
| | - Chengyu Wu
- Graduate School, Xinjiang Medical University, Urumqi, Xinjiang, People's Republic of China
| | - Naixue Wang
- Nantong Sixth People's Hospital, Nantong, Jiangsu, People's Republic of China
| | - Shu Lu
- Nantong University Hospital, Nantong, Jiangsu, People's Republic of China.
- Member of the Critical Care Medicine Branch of Jiangsu Physicians Association, Member of the Critical Care Ultrasound Group of Jiangsu Medical Association, Member of the Critical Care Medicine Branch of Nantong Medical Association, Member of Nantong Critical Care Medicine Quality Control Center, Affiliated Hospital of Nantong University, No. 20 Xisi Road, Nantong, 226000, Jiangsu, People's Republic of China.
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Thy M, Sonneville R, Ruckly S, Mourvillier B, Schwebel C, Cohen Y, Garrouste-Orgeas M, Siami S, Bruel C, Reignier J, Azoulay E, Argaud L, Goldgran-Toledano D, Laurent V, Dupuis C, Poujade J, Bouadma L, de Montmollin E, Timsit JF. Early systemic insults following severe sepsis-associated encephalopathy of critically ill patients: association with mortality and awakening-an analysis of the OUTCOMEREA database. J Intensive Care 2025; 13:5. [PMID: 39810227 PMCID: PMC11730477 DOI: 10.1186/s40560-024-00773-9] [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: 10/20/2024] [Accepted: 12/28/2024] [Indexed: 01/16/2025] Open
Abstract
BACKGROUND Sepsis-associated encephalopathy (SAE) may be worsened by early systemic insults. We aimed to investigate the association of early systemic insults with outcomes of critically ill patients with severe SAE. METHODS We performed a retrospective analysis using data from the French OUTCOMEREA prospective multicenter database. We included patients hospitalized in intensive care unit (ICU) for at least 48 h with severe SAE (defined by a score on the Glasgow Coma Scale (GCS) ≤ 13 and severe sepsis or septic shock (SEPSIS 2.0 criteria)) requiring invasive ventilation and who had no primary brain injury. We analyzed early systemic insults (abnormal glycemia (< 3 mmol/L or ≥ 11 mmol/L), hypotension (diastolic blood pressure ≤ 50 mmHg), temperature abnormalities (< 36 °C or ≥ 38.3 °C), anemia (hematocrit < 21%), dysnatremia (< 135 mmol/L or ≥ 145 mmol/L), oxygenation abnormalities (PaO2 < 60 or > 200 mmHg), carbon dioxide abnormalities (< 35 mmHg or ≥ 45 mmHg), and the impact of their correction at day 3 on day-28 mortality and awakening, defined as a recovery of GCS > 13. RESULTS We included 995 patients with severe SAE, of whom 883 (89%) exhibited at least one early systemic insult that persisted through day 3. Compared to non-survivors, survivors had significantly less early systemic insults (hypoglycemia, hypotension, hypothermia, and anemia) within the first 48 h of ICU admission. The absence of correction of the following systemic insults at day 3 was independently associated with mortality: blood pressure (adjusted hazard ratio (aHR) = 1.77, 95% confidence interval (CI) 1.34-2.34), oxygenation (aHR = 1.78, 95% CI 1.20-2.63), temperature (aHR = 1.46, 95% CI 1.12-1.91) and glycemia (aHR = 1.41, 95% CI 1.10-1.80). Persistent abnormal blood pressure, temperature and glycemia at day 3 were associated with decreased chances of awakening. CONCLUSIONS In patients with severe SAE, the persistence of systemic insults within the first three days of ICU admission is associated with increased mortality and decreased chances of awakening.
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Affiliation(s)
- Michael Thy
- Medical and Infectious Diseases, ICU, Hospital Bichat-Claude Bernard, Université Paris Cité, AP-HP, Paris, France.
- UMR 1343, Pharmacology and Therapeutic Evaluation in Children and Pregnant Women, INSERM, Université Paris Cité, Paris, France.
- UMR 1137, INSERM, Université Paris Cité, Paris, France.
| | - Romain Sonneville
- Medical and Infectious Diseases, ICU, Hospital Bichat-Claude Bernard, Université Paris Cité, AP-HP, Paris, France
- UMR 1137, INSERM, Université Paris Cité, Paris, France
| | - Stéphane Ruckly
- UMR 1137, INSERM, Université Paris Cité, Paris, France
- OUTCOME REA Network, Drancy, France
| | | | - Carole Schwebel
- Medical Intensive Care Unit, C.H.U de Grenoble, La Tronche, France
| | - Yves Cohen
- Respiratory Department, Avicenne Hospital (AP-HP), Bobigny, France
| | - Maité Garrouste-Orgeas
- Intensive Care Unit, Hospital Franco-Britannique, Fondation Cognacq-Jay, Levallois-Perret, France
| | - Shidasp Siami
- Réanimation, Hospital Center Sud Essonne, Étampes, France
| | - Cédric Bruel
- Medical and Surgical Intensive Care Unit, Hospital Paris Saint-Joseph, Paris, France
| | - Jean Reignier
- Intensive Care Unit, Nantes University Hospital Hotel-Dieu, Nantes, France
| | - Elie Azoulay
- Medical Intensive Care Unit, Hospital Saint-Louis, Paris, France
| | - Laurent Argaud
- Intensive Care Unit, Hospital Édouard Herriot, Lyon, France
| | - Dany Goldgran-Toledano
- Intensive Care Unit, Intercommunal Hospital Group Le Raincy Montfermeil, Montfermeil, France
| | | | - Claire Dupuis
- Intensive Care Unit, CHU Gabriel-Montpied, Clermont-Ferrand, France
| | - Julien Poujade
- Medical and Infectious Diseases, ICU, Hospital Bichat-Claude Bernard, Université Paris Cité, AP-HP, Paris, France
| | - Lila Bouadma
- Medical and Infectious Diseases, ICU, Hospital Bichat-Claude Bernard, Université Paris Cité, AP-HP, Paris, France
- UMR 1137, INSERM, Université Paris Cité, Paris, France
| | - Etienne de Montmollin
- Medical and Infectious Diseases, ICU, Hospital Bichat-Claude Bernard, Université Paris Cité, AP-HP, Paris, France
- UMR 1137, INSERM, Université Paris Cité, Paris, France
| | - Jean-François Timsit
- Medical and Infectious Diseases, ICU, Hospital Bichat-Claude Bernard, Université Paris Cité, AP-HP, Paris, France
- UMR 1137, INSERM, Université Paris Cité, Paris, France
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Kobayashi E, Shiraishi A, Karumai T, Hayashi Y, Abe T, Ogura H, Shigeki K, Gando S, Okamoto K, Umemura Y, Sasaki J, Shiino Y, Mayumi T. Carbapenem Usage in the Initial Antibiotic Therapy of Sepsis in Japanese Intensive Care Units. Cureus 2025; 17:e77271. [PMID: 39931585 PMCID: PMC11809119 DOI: 10.7759/cureus.77271] [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] [Accepted: 12/26/2024] [Indexed: 02/13/2025] Open
Abstract
Background Achieving a balance between the utilization and limitation of carbapenems for initial sepsis therapy is imperative, yet documentation on the use of carbapenems in sepsis treatment is limited. This study aimed to ascertain the prevalence of carbapenem use in Japanese intensive care units (ICUs) and evaluate the association between its use in the initial antibiotic therapy for sepsis and patient prognosis. Methods This study is a post hoc descriptive analysis of the Focused Outcome Research on Emergency Care for Acute Respiratory Distress Syndrome, Sepsis, and Trauma (FORECAST), a multicenter, prospective cohort study conducted in 59 ICUs in Japan from January 2016 to March 2017. This study described the rate of carbapenem use overall and in each ICU and assessed the association between carbapenem use and in-hospital mortality by generalized linear mixed effect model adjusting for patient characteristics as fixed effect confounders and the hospitals as random effect confounders. Results Out of 1140 participants, 627(55.0%) received and 513 (45.0%) did not receive carbapenems following the diagnosis of severe sepsis or septic shock. Patient severity was similar in both groups in terms of Sepsis-related Organ Failure Assessment (SOFA; 9 and 8) and Acute Physiology and Chronic Health Evaluation II (APACHE II; 23 and 22) scores. Among 48 of the 59 ICUs that registered more than three patients in the FORECAST registry, the median carbapenem utilization rate stood at 55.2% (minimum: 20.0%, maximum: 100.0%, IQR: 43.6%-67.2%). Hospital mortality rates were 25.6% and 20.5% in carbapenem recipients and non-recipients, respectively. A correlation between initial carbapenem use and increased in-hospital mortality was discerned in the unadjusted model (difference of 5.2%), but this association was not evident in the adjusted model (difference of 1.2%; 95%CI: -4.3,6.6; p=0.66). Conclusions Initial antibiotic therapy with carbapenems was noted in over half of the sepsis patients in Japanese ICUs. In-hospital mortality was not associated with the use of carbapenems.
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Affiliation(s)
- Eri Kobayashi
- Department of Emergency and Critical Care, Saiseikai Utsunomiya Hospital, Utsunomiya, JPN
| | | | - Toshiyuki Karumai
- Department of Intensive Care Medicine, Kameda Medical Center, Kamogawa, JPN
| | - Yoshiro Hayashi
- Department of Intensive Care Medicine, Kameda Medical Center, Kamogawa, JPN
| | - Toshikazu Abe
- Department of Emergency and Critical Care Medicine, Tsukuba Memorial Hospital, Ibaraki, JPN
| | - Hiroshi Ogura
- Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, JPN
| | - Kushimoto Shigeki
- Division of Emergency and Critical Care Medicine, Tohoku University Graduate School of Medicine, Sendai, JPN
| | - Satoshi Gando
- Division of Acute and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Hokkaido University Faculty of Medicine, Sapporo, JPN
| | - Kohji Okamoto
- Department of Surgery, Center for Gastroenterology and Liver Disease, Kitakyushu City Yahata Hospital, Kitakyushu, JPN
| | - Yutaka Umemura
- Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, JPN
| | - Junichi Sasaki
- Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Shinjuku, JPN
| | - Yasukazu Shiino
- Department of Acute Medicine, Kawasaki Medical School, Okayama, JPN
| | - Toshihiko Mayumi
- Department of Emergency Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, JPN
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Noureldeen H, Bakhsh A, Alshabasy A, Alawi M, Bakhribah A, Nasrallah N, Aljuhani O, Margushi R, Bantan R, Bokhari R, Idris S, Alshamrani L, Samman A, Alharthi E, Alothman A. Enhancing Sepsis Care at an Academic Emergency Department in a Resource-Constrained Setting: A Quality Improvement Initiative. J Patient Saf 2025; 21:24-29. [PMID: 39412425 DOI: 10.1097/pts.0000000000001289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2024]
Abstract
OBJECTIVES The early recognition of sepsis and septic shock is crucial for improved patient outcomes. Quality improvement programs have ameliorated processes and outcomes in the care of patients with sepsis and septic shock. This study aimed to improve the proportion of patients receiving antibiotics within 1 hour of triage and compliance with sepsis bundles. METHODS A multidisciplinary sepsis task force was created to monitor and improve sepsis care. The program lasted 24 months from January 1, 2018, to December 31, 2019. A unique screening criterion was created by combining items from the systemic inflammatory response syndrome, quick sequential organ failure assessment, and National Early Warning Score systems. Thereafter, a sepsis flowsheet was implemented in the emergency department for monitoring. The measures between the first 12 months and the last 12 months were compared. RESULTS The proportion of patients receiving antibiotics within 1 hour of triage improved from 44% to 84%, intravenous crystalloid administration within 3 hours improved from 62% to 94%, serum lactic acid measurement within 3 hours improved from 62% to 94%, and vasopressor initiation within 6 hours improved from 76% to 94%. The mortality rates decreased from 32% to 21% between the 2 study periods. CONCLUSIONS This program emphasizes the impact of a structured quality improvement program on the process and outcomes of care.
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Affiliation(s)
| | | | | | - Maha Alawi
- Medical Microbiology and Parasitology, Infection Control and Environmental Health Unit, Faculty of Medicine, King Abdulaziz University
| | | | - Nihad Nasrallah
- Department of Nursing Administration, King Abdulaziz University Hospital
| | | | - Rahaf Margushi
- Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Rafal Bantan
- Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Raneem Bokhari
- Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Sarah Idris
- Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Lamis Alshamrani
- Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Abeer Samman
- Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Elaf Alharthi
- Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Ali Alothman
- From the Department of Anesthesia and Critical Care Medicine, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
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Vasquez MP, Daly M, Boyd CJ, Crandell DE, Hall KE, Mays EL, Ngwenyama T, Ortolani J, Smith MR, Hoehne SN, Martin L, Davidow EB. Multicenter retrospective evaluation of norepinephrine extravasation in dogs and cats (2015-2021): 14 cases. J Vet Emerg Crit Care (San Antonio) 2025; 35:73-80. [PMID: 39957707 DOI: 10.1111/vec.13442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 10/27/2023] [Accepted: 11/04/2023] [Indexed: 02/18/2025]
Abstract
OBJECTIVE To document clinical complications and intervention options associated with norepinephrine (NE) extravasation in dogs and cats. DESIGN Cases were identified between 2015 and 2021. Because this is an uncommon complication, the findings are compiled as a descriptive retrospective study. SETTING Cases were provided from 4 universities and 2 private practice groups in the United States, Canada, and Australia. ANIMALS Fourteen patients (13 dogs, 1 cat) that experienced extravasation events (16 total). INTERVENTIONS Small animal patients were included where extravasation of a NE constant rate infusion (CRI) was documented. Records were reviewed for information, including suspected underlying condition, description of the interventions pursued after identification of extravasation, clinical signs after extravasation, and survival to discharge or reason for patient death or euthanasia. When available, information was collected pertaining to the NE dose, dilution, total duration of CRI, and duration of CRI before extravasation was recognized. MEASUREMENTS AND MAIN RESULTS The most commonly reported clinical signs after extravasation of NE were skin necrosis (n = 9 [64.3%]) and swelling (n = 6 [42.9%]). In 10 of 16 events (62.5%), discontinuation of the NE CRI and/or application of a warm compress to the extravasation site were performed; these were the most common nonpharmacological rescue measures. Two patients received subcutaneous phentolamine, and 1 patient underwent hyperbaric oxygen therapy. While surgical intervention was recommended for 4 dogs, 2 improved without surgical debridement. The overall survival rate from underlying disease processes was 57% (n = 8), with only 1 patient (7%) euthanized due to an injury from the extravasation. CONCLUSIONS Severe lesions can result from NE extravasation in dogs and cats, leading to euthanasia. Although phentolamine remains the treatment of choice, lesions may heal with alternative supportive measures.
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Affiliation(s)
- Maria P Vasquez
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA
| | | | - Corrin J Boyd
- School of Veterinary Medicine, Murdoch University, Murdoch, Western Australia, Australia
| | | | - Kelly E Hall
- Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado, USA
| | - Erin Long Mays
- Department of Veterinary Clinical Medicine, University of Illinois Urbana-Champaign, Urbana, Illinois, USA
| | - Tandi Ngwenyama
- Oregon State University Veterinary Teaching Hospital, Corvallis, Oregon, USA
| | - Jennifer Ortolani
- VCA SouthPaws Veterinary Specialists and Emergency Center, Fairfax, Virginia, USA
| | - M Ryan Smith
- Department of Veterinary Clinical Sciences, Louisiana State University, Baton Rouge, Louisiana, USA
| | - Sabrina N Hoehne
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA
| | - Linda Martin
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA
| | - Elizabeth B Davidow
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA
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Alladina J. When Less Is More - Revisiting Hemodynamic Targets in Vasodilatory Shock. NEJM EVIDENCE 2025; 4:EVIDe2400388. [PMID: 39718429 DOI: 10.1056/evide2400388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/25/2024]
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Xu L, Zhao W, He J, Hou S, He J, Zhuang Y, Wang Y, Yang H, Xiao J, Qiu Y. Abdominal perfusion pressure is critical for survival analysis in patients with intra-abdominal hypertension: mortality prediction using incomplete data. Int J Surg 2025; 111:371-381. [PMID: 39166944 PMCID: PMC11745648 DOI: 10.1097/js9.0000000000002026] [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: 06/09/2024] [Accepted: 07/30/2024] [Indexed: 08/23/2024]
Abstract
BACKGROUND Abdominal perfusion pressure (APP) is a salient feature in the design of a prognostic model for patients with intra-abdominal hypertension (IAH). However, incomplete data significantly limits the size of the beneficiary patient population in clinical practice. Using advanced artificial intelligence methods, the authors developed a robust mortality prediction model with APP from incomplete data. METHODS The authors retrospectively evaluated the patients with IAH from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Incomplete data were filled in using generative adversarial imputation nets (GAIN). Lastly, demographic, clinical, and laboratory findings were combined to build a 7-day mortality prediction model. RESULTS The authors included 1354 patients in this study, of which 63 features were extracted. Data imputation with GAIN achieved the best performance. Patients with an APP <60 mmHg had significantly higher all-cause mortality within 7-90 days. The difference remained significant in long-term survival even after propensity score matching (PSM) eliminated other mortality risks between groups. Lastly, the built machine learning model for 7-day modality prediction achieved the best results with an AUC of 0.80 in patients with confirmed IAH outperforming the other four traditional clinical scoring systems. CONCLUSIONS APP reduction is an important survival predictor affecting the survival prognosis of patients with IAH. The authors constructed a robust model to predict the 7-day mortality probability of patients with IAH, which is superior to the commonly used clinical scoring systems.
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Affiliation(s)
- Liang Xu
- Department of General Surgery, The Second Affiliated Hospital of the Army Medical University
- Bio-Med Informatics Research Centre and Clinical Research Centre, The Second Affiliated Hospital of the Army Medical University
| | - Weijie Zhao
- Bioengineering College, Chongqing University
| | - Jiao He
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University
| | - Siyu Hou
- Bio-Med Informatics Research Centre and Clinical Research Centre, The Second Affiliated Hospital of the Army Medical University
| | - Jialin He
- Department of Gastroenterology, The Second Affiliated Hospital of the Army Medical University
| | - Yan Zhuang
- Medical Big Data Research Center, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Ying Wang
- Department of General Surgery, The Second Affiliated Hospital of the Army Medical University
| | - Hua Yang
- Department of General Surgery, Chongqing General Hospital, Chongqing
| | - Jingjing Xiao
- Bio-Med Informatics Research Centre and Clinical Research Centre, The Second Affiliated Hospital of the Army Medical University
| | - Yuan Qiu
- Department of General Surgery, The Second Affiliated Hospital of the Army Medical University
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Murata M, Shimizu S, Yamamoto R, Kamitani T, Yamazaki H, Ogawa Y, Fukuhara S, Yasuda H, Yamamoto Y. Steroid Therapy for Patients with Septic Shock: A Multicenter Observational Study Conducted in Japan. Intern Med 2024; 63:3307-3315. [PMID: 38719604 PMCID: PMC11729175 DOI: 10.2169/internalmedicine.1511-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Accepted: 02/25/2024] [Indexed: 12/17/2024] Open
Abstract
Objective The Clinical Practice Guidelines for the Management of Sepsis and Septic Shock weakly recommend steroids for septic shock resistant to fluid resuscitation and vasopressors. This study aimed to describe the clinical practices for septic shock in the real world and to compare the association between the intermittent or continuous infusion of steroids and the prognosis. Methods This was a retrospective cohort study based on the AMOR-VENUS, in which Japanese intensive care unit (ICU) inpatients were enrolled between January and March 2018. Adult patients with sepsis who received vasopressors within 72 h of ICU admission were included. The patients were divided into non-steroid and steroid groups, which were further divided into intermittent and continuous infusion groups. The patient characteristics and details of the steroids are described. To investigate the association between intermittent or continuous infusion, shock reversal, and mortality, logistic regression analyses were performed after adjusting for possible confounding factors. Results A total of 180 patients with septic shock from 18 ICUs were enrolled. The mean age was 69.6 (standard deviation, 14.3) years. Sixty-three patients (35.0%) received steroids (26 intermittently, 37 continuously). In the steroid group, hydrocortisone was used in 85.7%, the median daily dose was 192 mg, and the steroids were administered within 6 h of initiating vasopressor in 71.4%. The adjusted odds ratios of shock reversal on the 7th day and the ICU mortality for continuous versus intermittent infusion were 1.90 (95% confidence interval, 0.43-8.40) and 0.61 (0.10-3.85), respectively. Conclusion There was considerable variation in the criteria for the selection of patients and in the decision to use continuous or intermittent steroid infusion.
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Affiliation(s)
- Maki Murata
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Japan
| | - Sayaka Shimizu
- Institute for Health Outcomes & Process Evaluation Research (iHope International), Japan
- Section of Clinical Epidemiology, Department of Community Medicine, Graduate School of Medicine, Kyoto University, Japan
| | - Ryohei Yamamoto
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Japan
| | - Tsukasa Kamitani
- Section of Education for Clinical Research, Kyoto University Hospital, Japan
| | - Hajime Yamazaki
- Section of Clinical Epidemiology, Department of Community Medicine, Graduate School of Medicine, Kyoto University, Japan
| | - Yusuke Ogawa
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Japan
| | - Shunichi Fukuhara
- Institute for Health Outcomes & Process Evaluation Research (iHope International), Japan
- Center for Innovative Research for Communities and Clinical Excellence, Fukushima Medical University, Japan
- Department of General Medicine, Shirakawa Satellite for Teaching And Research (STAR), Fukushima Medical University, Japan
- Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health (JHSPH), USA
| | - Hideto Yasuda
- Department of Emergency and Critical Care Medicine, Jichi Medical University Saitama Medical Center, Japan
- Department of Clinical Research Education and Training Unit, Keio University Hospital Clinical and Translational Research Center 17 (CTR), Japan
| | - Yosuke Yamamoto
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Japan
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Guo Q, Li HY, Song WD, Li M, Chen XK, Liu H, Peng HL, Yu HQ, Liu N, Li YH, Lü ZD, Liang LH, Zhao QZ, Jiang M. Contributions of individual qSOFA elements to assessment of severity and for prediction of mortality. Ann Med 2024; 56:2397090. [PMID: 39221748 PMCID: PMC11370683 DOI: 10.1080/07853890.2024.2397090] [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: 07/12/2023] [Revised: 04/12/2024] [Accepted: 04/12/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND The quick sequential [sepsis-related] organ failure assessment (qSOFA) acts as a prompt to consider possible sepsis. The contributions of individual qSOFA elements to assessment of severity and for prediction of mortality remain unknown. METHODS A total of 3974 patients with community-acquired pneumonia were recruited to an observational prospective cohort study. The area under the receiver operating characteristic curve (AUROC), odds ratio, relative risk and Youden's index were employed to assess discrimination. RESULTS Respiratory rate ≥22/min demonstrated the most superior diagnostic value, indicated by largest odds ratio, relative risk and AUROC, and maximum Youden's index for mortality. However, the indices for altered mentation and systolic blood pressure (SBP) ≤100 mm Hg decreased notably in turn. The predictive validities of respiratory rate ≥22/min, altered mentation and SBP ≤100 mm Hg were good, adequate and poor for mortality, indicated by AUROC (0.837, 0.734 and 0.671, respectively). Respiratory rate ≥22/min showed the strongest associations with SOFA scores, pneumonia severity index, hospital length of stay and costs. However, SBP ≤100 mm Hg was most weakly correlated with the indices. CONCLUSIONS Respiratory rate ≥22/min made the greatest contribution to parsimonious qSOFA to assess severity and predict mortality. However, the contributions of altered mentation and SBP ≤100 mm Hg decreased strikingly in turn. It is the first known prospective evidence of the contributions of individual qSOFA elements to assessment of severity and for prediction of mortality, which might have implications for more accurate clinical triage decisions.
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Affiliation(s)
- Qi Guo
- Department of Pulmonary and Critical Care Medicine, Shenzhen Hospital, Peking University, Shenzhen, Guangdong, China
- Department of Pulmonary and Critical Care Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China
| | - Hai-yan Li
- Department of General Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China
| | - Wei-dong Song
- Department of Pulmonary and Critical Care Medicine, Shenzhen Hospital, Peking University, Shenzhen, Guangdong, China
| | - Ming Li
- Department of Pulmonary and Critical Care Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China
| | - Xiao-ke Chen
- Department of Pulmonary and Critical Care Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China
| | - Hui Liu
- Department of Pulmonary and Critical Care Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China
| | - Hong-lin Peng
- Department of Pulmonary and Critical Care Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China
| | - Hai-qiong Yu
- Department of Pulmonary and Critical Care Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China
| | - Nian Liu
- Department of Pulmonary and Critical Care Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China
| | - Yan-hong Li
- Department of Pulmonary and Critical Care Medicine, Shenzhen Hospital, Peking University, Shenzhen, Guangdong, China
| | - Zhong-dong Lü
- Department of Pulmonary and Critical Care Medicine, Shenzhen Hospital, Peking University, Shenzhen, Guangdong, China
| | - Li-hua Liang
- Department of Radiology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China
| | - Qing-zhou Zhao
- Department of Radiology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China
| | - Mei Jiang
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
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Sharma S, Paneru HR, Shrestha GS, Shrestha PS, Acharya SP. Evaluation of the Effects of a Combination of Vitamin C, Thiamine and Hydrocortisone vs Hydrocortisone Alone on ICU Outcome in Patients with Septic Shock: A Randomized Controlled Trial. Indian J Crit Care Med 2024; 28:1147-1152. [PMID: 39759781 PMCID: PMC11695884 DOI: 10.5005/jp-journals-10071-24852] [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: 09/09/2024] [Accepted: 10/25/2024] [Indexed: 01/07/2025] Open
Abstract
Aims and background Glucocorticoids, vitamin C and thiamine have important biological effects in patients with sepsis and septic shock. Multiple studies have demonstrated the beneficial role of a combination therapy of vitamin C, hydrocortisone and thiamine in patients with sepsis and septic shock in terms of mortality reduction, and increase in the number of days free of ventilators and vasopressors. Materials and methods Patients who had septic shock were assessed for eligibility after intensive care unit (ICU) admission. After randomization, the treatment group received a combination of vitamin C, thiamine and hydrocortisone for a duration of 96 hours (16 doses) and the control group received hydrocortisone for a duration till the patient was on vasopressors. The primary outcome assessed was ICU mortality, and the key secondary outcome was the duration free of vasopressor administration at the end of 7 days. Results A total of 86 patients were included in the study. Seventy percent of patients in the control group and 58 percent in the intervention group died during ICU stay. None of the primary and secondary outcomes were statistically significant. Conclusion The use of a combination of vitamin C, hydrocortisone and thiamine has no added benefits over the use of hydrocortisone alone in patients with septic shock. Clinical significance The results of this clinical trial shows that the use of a combination of vitamin C, hydrocortisone and thiamine in patients with septic shock is not useful and should not be a routine practice in critically ill septic patients. How to cite this article Sharma S, Paneru HR, Shrestha GS, Shrestha PS, Acharya SP. Evaluation of the Effects of a Combination of Vitamin C, Thiamine and Hydrocortisone vs Hydrocortisone Alone on ICU Outcome in Patients with Septic Shock: A Randomized Controlled Trial. Indian J Crit Care Med 2024;28(12):1147-1152.
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Affiliation(s)
- Sachit Sharma
- Department of Critical Care Medicine, Tribhuvan University Teaching Hospital, Institute of Medicine, Kathmandu, Bagmati, Nepal
| | - Hem R Paneru
- Department of Critical Care Medicine, Tribhuvan University Teaching Hospital, Institute of Medicine, Kathmandu, Bagmati, Nepal
| | - Gentle S Shrestha
- Department of Critical Care Medicine, Tribhuvan University Teaching Hospital, Institute of Medicine, Kathmandu, Bagmati, Nepal
| | - Pramesh S Shrestha
- Department of Critical Care Medicine, Tribhuvan University Teaching Hospital, Institute of Medicine, Kathmandu, Bagmati, Nepal
| | - Subhash P Acharya
- Department of Critical Care Medicine, Tribhuvan University Teaching Hospital, Institute of Medicine, Kathmandu, Bagmati, Nepal
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Counts JP, Arnold J, Atyia S, Ogake S, Smith RM, Doepker B. The Effect of Albumin Replacement on Vasopressor Duration in Septic Shock in Patients With Hypoalbuminemia. Ann Pharmacother 2024; 58:1179-1186. [PMID: 38486351 DOI: 10.1177/10600280241236507] [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: 10/27/2024] Open
Abstract
BACKGROUND The use of albumin resuscitation in septic shock is only recommended in patients who have received large volumes of crystalloid resuscitation regardless of serum albumin concentration. The role of albumin is still largely debated and evidence to support its use still lacking. OBJECTIVE The objective of this study was to evaluate whether albumin replacement increases the number of vasopressor-free days in patients with septic shock and hypoalbuminemia. METHODS A retrospective analysis was conducted to assess the effect of albumin replacement in septic shock. Hypoalbuminemic patients with septic shock who received albumin were retrospectively compared with a cohort who did not. The primary outcome was number of vasopressor-free days at day 14 from shock presentation, which was analyzed using an adjusted linear regression model to adjust for confounders. RESULTS There was no difference in vasopressor-free days at day 14 in patients who received albumin versus those who did not, after adjusting for confounders of exposure (0.50, 95% CI = -0.97 to 1.97; P = 0.502). There also was no difference in secondary outcomes except for need for invasive mechanical ventilation (MV), which was significantly lower in patients who received albumin (61 [54.4%] vs 88 [67.7%]; P = 0.035). CONCLUSIONS AND RELEVANCE We observed no difference in vasopressor-free days at day 14 in patients with hypoalbuminemia who received albumin compared with those who did not. However, patients who received albumin required significantly less MV although further studies are warranted to assess this effect.
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Affiliation(s)
- Jacob P Counts
- Department of Pharmacy, Wexner Medical Center, The Ohio State University, Columbus, OH, USA
| | - Joshua Arnold
- Department of Pharmacy, Wexner Medical Center, The Ohio State University, Columbus, OH, USA
| | - Sara Atyia
- Department of Pharmacy, MetroHealth Medical Center, Cleveland, OH, USA
| | - Stella Ogake
- Division of Pulmonary, Critical Care and Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Rachel M Smith
- The Ohio State University Center for Biostatistics, Columbus, OH, USA
| | - Bruce Doepker
- Department of Pharmacy, Wexner Medical Center, The Ohio State University, Columbus, OH, USA
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Zhou Y, He LP, Qi YH, Huang Y, Hu BQ, Liu JL, Zeng QB, Song JC. Diagnostic value of tissue plasminogen activator-inhibitor complex in sepsis-induced liver injury: A single-center retrospective case-control study. World J Hepatol 2024; 16:1255-1264. [PMID: 39606162 PMCID: PMC11586747 DOI: 10.4254/wjh.v16.i11.1255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Revised: 09/05/2024] [Accepted: 10/15/2024] [Indexed: 11/06/2024] Open
Abstract
BACKGROUND Sepsis often causes severe liver injury and leads to poor patient outcomes. Early detection of sepsis-induced liver injury (SILI) and early treatment are key to improving outcomes. AIM To investigate the clinical characteristics of SILI patients and analyze the associated risk factors, to identify potential sensitive biomarkers. METHODS Retrospective analysis of clinical data from 546 patients with sepsis treated in the intensive care unit of the 908th Hospital of Chinese People's Liberation Army Joint Logistic Support Force between May 2018 and December 2022. The patients were divided into the sepsis group (n = 373) and SILI group (n = 173) based on the presence of acute liver injury within 2 hours of admission. We used the random forest algorithm to analyze risk factors and assessed potential diagnostic markers of SILI using the area under the receiver operating characteristic curve, Kaplan-Meier survival curves, subgroup analysis and correlation analysis. RESULTS Compared with the sepsis group, tissue plasminogen activator-inhibitor complex (t-PAIC) levels in serum were significantly higher in the SILI group (P < 0.05). Random forest results showed that t-PAIC was an independent risk factor for SILI, with an area under the receiver operating characteristic curve of 0.862 (95% confidence interval: 0.832-0.892). Based on the optimal cut-off value of 11.9 ng/mL, patients at or above this threshold had significantly higher levels of lactate and Acute Physiology and Chronic Health Evaluation II score. The survival rate of these patients was also significantly worse (hazard ratio = 2.2, 95% confidence interval: 1.584-3.119, P < 0.001). Spearman's correlation coefficients were 0.42 between t-PAIC and lactate, and 0.41 between t-PAIC and aspartate transaminase. Subgroup analysis showed significant differences in t-PAIC levels between patients with different severity of liver dysfunction. CONCLUSION T-PAIC can serve as a diagnostic indicator for SILI, with its elevation correlated with the severity of SILI.
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Affiliation(s)
- Ye Zhou
- Department of Critical Care Medicine, Changcheng Hospital Affiliated to Nanchang University, Nanchang 330002, Jiangxi Province, China
- Department of Critical Care Medicine, The 908 Hospital of Chinese People's Liberation Army Joint Logistic Support Force, Nanchang 330002, Jiangxi Province, China
| | - Long-Ping He
- Department of Critical Care Medicine, Changcheng Hospital Affiliated to Nanchang University, Nanchang 330002, Jiangxi Province, China
| | - Ying-Han Qi
- Department of Critical Care Medicine, Changcheng Hospital Affiliated to Nanchang University, Nanchang 330002, Jiangxi Province, China
| | - Yu Huang
- Department of Critical Care Medicine, Changcheng Hospital Affiliated to Nanchang University, Nanchang 330002, Jiangxi Province, China
| | - Bing-Qin Hu
- Department of Critical Care Medicine, Changcheng Hospital Affiliated to Nanchang University, Nanchang 330002, Jiangxi Province, China
| | - Jia-Ling Liu
- Department of Critical Care Medicine, Changcheng Hospital Affiliated to Nanchang University, Nanchang 330002, Jiangxi Province, China
| | - Qing-Bo Zeng
- Intensive Care Unit, Nanchang Hongdu Hospital of Traditional Chinese Medicine, Nanchang 330002, Jiangxi Province, China
| | - Jing-Chun Song
- Department of Critical Care Medicine, Changcheng Hospital Affiliated to Nanchang University, Nanchang 330002, Jiangxi Province, China
- Department of Critical Care Medicine, The 908 Hospital of Chinese People's Liberation Army Joint Logistic Support Force, Nanchang 330002, Jiangxi Province, China.
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