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2.
Front Immunol ; 15: 1373876, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38715602

RESUMO

Objective: The objective of this study was to investigate the impact of electro-acupuncture (EA) on sepsis-related intestinal injury and its relationship with macrophage polarization. Methods: A sepsis model was established using cecal ligation and puncture (CLP) to assess the effectiveness of EA. The extent of pathological injury was evaluated using Chiu's score, the expression of ZO-1 and Ocludin, and the impact on macrophage polarization was examined through flow cytometry and immunofluorescence staining. The expression of spermidine, one type of polyamine, and ornithine decarboxylase (ODC) was measured using ELISA and PCR. Once the efficacy was determined, a polyamine depletion model was created, and the role of polyamines was reassessed by evaluating efficacy and observing macrophage polarization. Results: EA treatment reduced the Chiu's score and increased the expression of ZO-1 and Ocludin in the intestinal tissue of septic mice. It inhibited the secretion of IL-1ß and TNF-α, promoted the polarization of M2-type macrophages, increased the secretion of IL-10, and upregulated the expression of Arg-1, spermidine, and ODC. However, after depleting polyamines, the beneficial effects of EA on alleviating intestinal tissue damage and modulating macrophage polarization disappeared. Conclusion: The mechanism underlying the alleviation of intestinal injury associated with CLP-induced sepsis by EA involves with the promotion of M2-type macrophage polarization mediated by spermidine expression.


Assuntos
Modelos Animais de Doenças , Eletroacupuntura , Macrófagos , Poliaminas , Sepse , Animais , Sepse/terapia , Sepse/metabolismo , Sepse/imunologia , Camundongos , Macrófagos/imunologia , Macrófagos/metabolismo , Eletroacupuntura/métodos , Poliaminas/metabolismo , Masculino , Ativação de Macrófagos , Intestinos/patologia , Intestinos/imunologia , Camundongos Endogâmicos C57BL , Citocinas/metabolismo
3.
Crit Care Explor ; 6(5): e1082, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38694845

RESUMO

OBJECTIVES: To evaluate the relationship between early IV fluid volume and hospital outcomes, including death in-hospital or discharge to hospice, in septic patients with and without heart failure (HF). DESIGN: A retrospective cohort study using logistic regression with restricted cubic splines to assess for nonlinear relationships between fluid volume and outcomes, stratified by HF status and adjusted for propensity to receive a given fluid volume in the first 6 hours. An ICU subgroup analysis was performed. Secondary outcomes of vasopressor use, mechanical ventilation, and length of stay in survivors were assessed. SETTING: An urban university-based hospital. PATIENTS: A total of 9613 adult patients were admitted from the emergency department from 2012 to 2021 that met electronic health record-based Sepsis-3 criteria. Preexisting HF diagnosis was identified by the International Classification of Diseases codes. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 1449 admissions from patients with HF. The relationship between fluid volume and death or discharge to hospice was nonlinear in patients without HF, and approximately linear in patients with HF. Receiving 0-15 mL/kg in the first 6 hours was associated with lower likelihood of death or discharge to hospice compared with 30-45 mL/kg (odds ratio = 0.61; 95% CI, 0.41-0.90; p = 0.01) in HF patients, but no significant difference for non-HF patients. A similar pattern was identified in ICU admissions and some secondary outcomes. Volumes larger than 15-30 mL/kg for non-HF patients and 30-45 mL/kg for ICU-admitted non-HF patients were not associated with improved outcomes. CONCLUSIONS: Early fluid resuscitation showed distinct patterns of potential harm and benefit between patients with and without HF who met Sepsis-3 criteria. Restricted cubic splines analysis highlighted the importance of considering nonlinear fluid outcomes relationships and identified potential points of diminishing returns (15-30 mL/kg across all patients without HF and 30-45 mL/kg when admitted to the ICU). Receiving less than 15 mL/kg was associated with better outcomes in HF patients, suggesting small volumes may be appropriate in select patients. Future studies may benefit from investigating nonlinear fluid-outcome associations and a focus on other conditions like HF.


Assuntos
Hidratação , Insuficiência Cardíaca , Sepse , Humanos , Estudos Retrospectivos , Masculino , Feminino , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/mortalidade , Idoso , Pessoa de Meia-Idade , Hidratação/métodos , Sepse/mortalidade , Sepse/terapia , Estudos de Coortes , Mortalidade Hospitalar , Unidades de Terapia Intensiva , Tempo de Internação
4.
Crit Care Explor ; 6(5): e1087, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38709088

RESUMO

Large randomized trials in sepsis have generally failed to find effective novel treatments. This is increasingly attributed to patient heterogeneity, including heterogeneous cardiovascular changes in septic shock. We discuss the potential for machine learning systems to personalize cardiovascular resuscitation in sepsis. While the literature is replete with proofs of concept, the technological readiness of current systems is low, with a paucity of clinical trials and proven patient benefit. Systems may be vulnerable to confounding and poor generalization to new patient populations or contemporary patterns of care. Typical electronic health records do not capture rich enough data, at sufficient temporal resolution, to produce systems that make actionable treatment suggestions. To resolve these issues, we recommend a simultaneous focus on technical challenges and removing barriers to translation. This will involve improving data quality, adopting causally grounded models, prioritizing safety assessment and integration into healthcare workflows, conducting randomized clinical trials and aligning with regulatory requirements.


Assuntos
Aprendizado de Máquina , Medicina de Precisão , Sepse , Humanos , Sepse/terapia , Medicina de Precisão/métodos , Ressuscitação/métodos
5.
Crit Care Explor ; 6(5): e1085, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38709081

RESUMO

OBJECTIVES: We assessed the association of preexisting diabetes mellitus with all-cause mortality and organ support receipt in adult patients with sepsis. DESIGN: Population-based cohort study. SETTING: Ontario, Canada (2008-2019). POPULATION: Adult patients (18 yr old or older) with a first sepsis-related hospitalization episode. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main exposure of interest was preexisting diabetes (either type 1 or 2). The primary outcome was all-cause mortality by 90 days; secondary outcomes included receipt of invasive mechanical ventilation and new renal replacement therapy. We report adjusted (for baseline characteristics using standardization) risk ratios (RRs) alongside 95% CIs. A main secondary analysis evaluated the potential mediation by prior metformin use of the association between preexisting diabetes and all-cause mortality following sepsis. Overall, 503,455 adults with a first sepsis-related hospitalization episode were included; 36% had preexisting diabetes. Mean age was 73 years, and 54% of the cohort were females. Preexisting diabetes was associated with a lower adjusted risk of all-cause mortality at 90 days (RR, 0.81; 95% CI, 0.80-0.82). Preexisting diabetes was associated with an increased risk of new renal replacement therapy (RR, 1.53; 95% CI, 1.46-1.60) but not invasive mechanical ventilation (RR, 1.03; 95% CI, 1.00-1.05). Overall, 21% (95% CI, 19-28) of the association between preexisting diabetes and reduced risk of all-cause mortality was mediated by prior metformin use. CONCLUSIONS: Preexisting diabetes is associated with a lower risk of all-cause mortality and higher risk of new renal replacement therapy among adult patients with sepsis. Future studies should evaluate the underlying mechanisms of these associations.


Assuntos
Sepse , Humanos , Masculino , Feminino , Sepse/mortalidade , Sepse/terapia , Idoso , Estudos de Coortes , Ontário/epidemiologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Diabetes Mellitus/mortalidade , Diabetes Mellitus/epidemiologia , Respiração Artificial , Terapia de Substituição Renal , Adulto , Hospitalização/estatística & dados numéricos , Fatores de Risco
6.
Nanotheranostics ; 8(3): 270-284, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38577320

RESUMO

Though there have been developments in clinical care and management, early and accurate diagnosis and risk stratification are still bottlenecks in septic shock patients. Since septic shock is multifactorial with patient-specific underlying co-morbid conditions, early assessment of sepsis becomes challenging due to variable symptoms and clinical manifestations. Moreover, the treatment strategies are traditionally based on their progression and corresponding clinical symptoms, not personalized. The complex pathophysiology assures that a single biomarker cannot identify, stratify, and describe patients affected by septic shock. Traditional biomarkers like CRP, PCT, and cytokines are not sensitive and specific enough to be used entirely for a patient's diagnosis and prognosis. Thus, the need of the hour is a sensitive and specific biomarker after comprehensive analysis that may facilitate an early diagnosis, prognosis, and drug development. Integration of clinical data with metabolomics would provide means to understand the patient's condition, stratify patients better, and predict the clinical outcome.


Assuntos
Sepse , Choque Séptico , Humanos , Choque Séptico/diagnóstico , Sepse/diagnóstico , Sepse/terapia , Biomarcadores , Prognóstico , Citocinas
7.
BMC Pulm Med ; 24(1): 197, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649913

RESUMO

BACKGROUND: High-flow nasal cannula (HFNC) has emerged as a promising noninvasive method for delivering oxygen to critically ill patients, particularly those with sepsis and acute lung injury. However, uncertainties persist regarding its therapeutic benefits in this specific patient population. METHODS: This retrospective study utilized a propensity score-matched cohort from the Medical Information Mart in Intensive Care-IV (MIMIC-IV) database to explore the correlation between HFNC utilization and mortality in patients with sepsis-induced acute lung injury. The primary outcome was 28-day all-cause mortality. RESULTS: In the propensity score-matched cohort, the 28-day all-cause mortality rate was 18.63% (95 out of 510) in the HFNC use group, compared to 31.18% (159 out of 510) in the non-HFNC group. The use of HFNC was associated with a lower 28-day all-cause mortality rate (hazard ratio [HR] = 0.53; 95% confidence interval [CI] = 0.41-0.69; P < 0.001). HFNC use was also associated with lower ICU mortality (odds ratio [OR] = 0.52; 95% CI = 0.38-0.71; P < 0.001) and lower in-hospital mortality (OR = 0.51; 95% CI = 0.38-0.68; P < 0.001). Additionally, HFNC use was found to be associated with a statistically significant increase in both the ICU and overall hospitalization length. CONCLUSIONS: These findings indicate that HFNC may be beneficial for reducing mortality rates among sepsis-induced acute lung injury patients; however, it is also associated with longer hospital stays.


Assuntos
Lesão Pulmonar Aguda , Cânula , Mortalidade Hospitalar , Unidades de Terapia Intensiva , Oxigenoterapia , Pontuação de Propensão , Sepse , Humanos , Estudos Retrospectivos , Masculino , Sepse/mortalidade , Sepse/terapia , Sepse/complicações , Feminino , Pessoa de Meia-Idade , Idoso , Lesão Pulmonar Aguda/mortalidade , Lesão Pulmonar Aguda/terapia , Lesão Pulmonar Aguda/etiologia , Oxigenoterapia/métodos , Estado Terminal/mortalidade
8.
J Pak Med Assoc ; 74(3): 608-612, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38591316

RESUMO

OBJECTIVE: To assess associations between various clinic-demographic factors and clinical outcomes among patients treated for sepsis. METHODS: The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data of all patients aged >18 years diagnosed with sepsis from January to December 2019. Multivariable logistic regression was used to evaluate independent associations between predictors and outcomes. Data was analysed using R packages. RESULTS: Of the 1,136 patients, 621(54.6%) were male and 515(45.3%) were female. The overall mean age was 59.05±16.91 years. Female gender (odds ratio: 1.029; 95% confidence interval: 1.03-1.64) was found to be an independent predictor of septic shock, while hypertension (odds ratio0.75; 95% confidence interval: 0.59-0.95) emerged as a protective factor. Chronic kidney disease (odds ratio: 1.539; 95% confidence interval: 1.14-2.07) was an independent predictor of prolonged length of stay, while older age appeared to be protective (odds ratio: 0.98; 95% confidence interval: 0.98-0.99). Mortality was associated with a significantly lower odds of Escherichia coli on culture (odds ratio: 0.26; 95% confidence interval: 0.12-0.54). CONCLUSIONS: Independent associations were found between specific patient characteristics and adverse clinical outcomes.


Assuntos
Sepse , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Paquistão/epidemiologia , Centros de Atenção Terciária , Mortalidade Hospitalar , Sepse/epidemiologia , Sepse/terapia , Sepse/complicações
9.
Front Immunol ; 15: 1356869, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38558800

RESUMO

Sepsis is a multi-organ dysfunction characterized by an unregulated host response to infection. It is associated with high morbidity, rapid disease progression, and high mortality. Current therapies mainly focus on symptomatic treatment, such as blood volume supplementation and antibiotic use, but their effectiveness is limited. Th17/Treg balance, based on its inflammatory property, plays a crucial role in determining the direction of the inflammatory response and the regression of organ damage in sepsis patients. This review provides a summary of the changes in T-helper (Th) 17 cell and regulatory T (Treg) cell differentiation and function during sepsis, the heterogeneity of Th17/Treg balance in the inflammatory response, and the relationship between Th17/Treg balance and organ damage. Th17/Treg balance exerts significant control over the bloom and wanes in host inflammatory response throughout sepsis.


Assuntos
Sepse , Linfócitos T Reguladores , Humanos , Células Th17 , Progressão da Doença , Sepse/terapia
10.
Front Immunol ; 15: 1328667, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38576606

RESUMO

Sepsis remains a significant cause of mortality and morbidity worldwide, with limited effective treatment options. The T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) has emerged as a potential therapeutic target in various immune-related disorders. This narrative review aims to explore the role of TIM-3 in sepsis and evaluate its potential as a promising target for immunotherapy. We discuss the dynamic expression patterns of TIM-3 during sepsis and its involvement in regulating immune responses. Furthermore, we examine the preclinical studies investigating the regulation of TIM-3 signaling pathways in septic models, highlighting the potential therapeutic benefits and challenges associated with targeting TIM-3. Overall, this review emphasizes the importance of TIM-3 in sepsis pathogenesis and underscores the promising prospects of TIM-3-based immunotherapy as a potential strategy to combat this life-threatening condition.


Assuntos
Receptor Celular 2 do Vírus da Hepatite A , Sepse , Humanos , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Imunoterapia , Sepse/terapia , Transdução de Sinais
11.
Medicine (Baltimore) ; 103(17): e37940, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669408

RESUMO

Sepsis is caused by the body's dysregulated response to infection, which can lead to multiorgan injury and death. Patients with sepsis may develop acute cardiac dysfunction, termed septic cardiomyopathy, which is a global but reversible dysfunction of both sides of the heart. This narrative review discusses the mechanistic changes in the heart during septic cardiomyopathy, its diagnosis, existing treatment options regarding severity and course, and emerging treatment approaches. Although no standardized definition for septic cardiomyopathy exists, it is described as a reversible myocardial dysfunction that typically resolves within 7 to 10 days. Septic cardiomyopathy is often diagnosed based on electrocardiography, cardiac magnetic resonance imaging, biomarkers, and direct invasive and noninvasive measures of cardiac output. Presently, the treatment of septic cardiomyopathy is similar to that of sepsis, primarily focusing on acute interventions. Treatments for cardiomyopathy often include angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and diuretics. However, because of profound hypotension in sepsis, many cardiomyopathy treatments are contraindicated in patients with septic cardiomyopathy. Substantial efforts have been made to study the pathophysiological mechanisms and diagnostic options; however, the lack of a uniform definition for septic cardiomyopathy is challenging for physicians when considering treatments. Another challenge for physicians is that the treatment for septic cardiomyopathy has only focused on acute intervention, whereas the treatment for other cardiomyopathies has been provided on a long-term basis. A better understanding of the underlying mechanisms of septic cardiomyopathy may contribute to the development of a unified definition of the condition and novel treatment options.


Assuntos
Cardiomiopatias , Sepse , Humanos , Cardiomiopatias/diagnóstico , Cardiomiopatias/terapia , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , Sepse/diagnóstico , Sepse/complicações , Sepse/fisiopatologia , Sepse/terapia , Eletrocardiografia
12.
JCO Glob Oncol ; 10: e2300412, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38484192

RESUMO

PURPOSE: Sepsis is the main cause of nonrelapse mortality, and there are no published data on applicability of supportive care protocols from high-income countries such as Sri Lanka. The aim of the study was to investigate management and mortality of neutropenic episodes among Hemato-Oncology patients. MATERIALS AND METHODS: Retrospective analysis of clinical characteristics, management, morbidity, and mortality of neutropenic Hemato-Oncology patients presented to the Lanka Hospital Blood Cancer Centre from January 1, 2019 to December 31, 2019 was performed. RESULTS: A total of 169 neutropenic episodes were identified; 115 (68%) of such episodes were related to chemotherapy. Acute leukemia, lymphoproliferative disorders, and plasma cell disorders accounted for 23%, 69%, and 8% of patients, respectively. The median age of patients who had sepsis was 56 years, whereas that of those who had no sepsis was 53 years (P = .49). The median time to neutropenia was 9 days for those in the sepsis group compared with 8 days in the group that had no sepsis (0.64). The median neutrophil count in the group that had sepsis was 0.06, whereas it was 0.69 in the group that had no sepsis (P ≤ .05). The median time to commencement of antibiotics was 20 minutes. CONCLUSION: To our knowledge, this is the only documented study related to outcome and successful applicability of western supportive care protocols to Sri Lankan patients with neutropenia. In this study, we have shown that neutropenic sepsis can be successfully managed in the setting of limited resources with service development, following guidelines and staff training.


Assuntos
Neoplasias Hematológicas , Neoplasias , Neutropenia , Sepse , Humanos , Pessoa de Meia-Idade , Sri Lanka/epidemiologia , Estudos Retrospectivos , Região de Recursos Limitados , Neoplasias/complicações , Sepse/terapia , Sepse/tratamento farmacológico , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Neutropenia/induzido quimicamente , Neutropenia/diagnóstico , Neutropenia/complicações
13.
Sci Rep ; 14(1): 6667, 2024 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509149

RESUMO

Sepsis-associated acute respiratory distress syndrome (ARDS) is a life-threatening condition in critical care medicine for which there is a substantial need for early prognostic biomarkers of outcome. The present study seeks to link plasma renin levels and 30-day mortality in sepsis-associated ARDS patients treated at our institution. The Registry of Critical Illness (RoCI) prospectively enrolled patients from the intensive care units (ICU) within a single academic medical center, and a convenience sample of patients with sepsis-associated ARDS was analyzed from this cohort. This study was approved by the Mass General Brigham Institutional Review Boards (IRB) as part of the RoCI, and all procedures performed were in accordance with the ethical standards of the institutional board. From April 2012 to February 2019, a cohort of 32 adult sepsis-associated ARDS patients with 500 µL of plasma samples available on Day 0 and Day 3 of their ICU stay were enrolled. Renin levels were measured twice, on Day 0 and Day 3 via the direct renin enzyme-linked immunosorbent assay (ELISA EIA-525) by DRG diagnostics. Day 0 and Day 3 renin were statistically evaluated via logistic regression to predict 30-day mortality. Direct renin levels of 64 samples were assayed from 32 sepsis-associated ARDS patients (50% male; mean ± SD, 55 ± 13.8 years old). The 30-day hospital mortality rate was 59.4%. Patients who died within 30 days of admission were more likely to have an elevated Day 3 Renin (Odds ratio [OR] = 6, 95% CI 1.25-28.84) and have received vasopressors (OR = 13.33, 95% CI 1.43-123.95). Adjusting for vasopressor use as a proxy for septic shock status, patients with an Elevated Day 3 Renin had a 6.85 (95% CI 1.07-43.75) greater odds of death than those with Low-Normal Day 3 Renin. Patients with sustained Elevated Renin levels from Day 0 to Day 3 had the highest risk of death in a 30-day window. In this study, we found that renin may be a novel biomarker that has prognostic value for patients with sepsis-associated ARDS. Future studies evaluating renin levels in patients with sepsis-associated ARDS are needed to validate these findings.


Assuntos
Síndrome do Desconforto Respiratório , Sepse , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Renina , Prognóstico , Sepse/complicações , Sepse/terapia , Unidades de Terapia Intensiva , Biomarcadores
14.
Acta Biomater ; 179: 83-94, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38447809

RESUMO

The terminal protein in the complement cascade C5a is a potent inflammatory molecule and chemoattractant that is involved in the pathology of multiple inflammatory diseases including sepsis and arthritis, making it a promising protein to target with immunotherapies. Active immunotherapies, in which patients are immunized against problematic self-molecules and generate therapeutic antibodies as a result, have received increasing interest as an alternative to traditional monoclonal antibody treatments. In previous work, we have designed supramolecular self-assembling peptide nanofibers as active immunotherapies with defined combinations of B- and T-cell epitopes. Herein, the self-assembling peptide Q11 platform was employed to generate a C5a-targeting active immunotherapy. Two of three predicted B-cell epitope peptides from C5a were found to be immunogenic when displayed within Q11 nanofibers, and the nanofibers were capable of reducing C5a serum concentrations following immunization. Contrastingly, C5a's precursor protein C5 maintained its original concentration, promising to minimize side effects heretofore associated with C5-targeted therapies. Immunization protected mice against an LPS-challenge model of sepsis, and it reduced clinical severity in a model of collagen-antibody induced arthritis. Together, this work indicates the potential for targeting terminal complement proteins with active immunotherapies by leveraging the immunogenicity of self-assembled peptide nanomaterials. STATEMENT OF SIGNIFICANCE: Chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease are currently treated primarily with monoclonal antibodies against key inflammatory mediators. While helpful for many patients, they have high non-response rates, are costly, and commonly fail as anti-drug antibodies are raised by the patient. The approach we describe here explores a fundamentally different treatment paradigm: raising therapeutic antibody responses with an active immunotherapy. We employ innovative supramolecular peptide nanomaterials to elicit neutralizing antibody responses against complement component C5a and demonstrate therapeutic efficacy in preclinical mouse models of sepsis and rheumatoid arthritis. The strategy reported may represent a potential alternative to monoclonal antibody therapies.


Assuntos
Complemento C5a , Imunoterapia , Inflamação , Nanofibras , Peptídeos , Animais , Nanofibras/química , Complemento C5a/imunologia , Peptídeos/química , Peptídeos/imunologia , Peptídeos/farmacologia , Imunoterapia/métodos , Inflamação/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Sepse/imunologia , Sepse/terapia , Artrite Experimental/imunologia , Artrite Experimental/terapia , Artrite Experimental/patologia
15.
Medicine (Baltimore) ; 103(12): e37380, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38518030

RESUMO

The literature study was conducted by using the Web of Science (WoS) database, employing bibliometric analysis to examine all papers released from 1980 to 2020. The search was performed using the terms "sepsis, septicemia, septic shock" specifically within the titles of the publications. The findings of the literature research revealed a total of 51,725 articles. Out of the total number of publications, 26,896 articles were identified, accounting for 51.9% of the total. The bibliometric study revealed that the United States had the largest number of papers (8693), followed by China (2807), Germany (2299), France (1606), and the United Kingdom (1932). The writers that exhibited the most prolific output in terms of article production on the topic of sepsis were Vincent, with a total of 217 articles, followed by Wang P with 154 articles, and Chaudry IH with 126 articles. The University of Pittsburgh, Brown University, and the University of Michigan were identified as the most productive universities, in that order. The findings from the prediction model revealed that the projected number of articles to be published in 2021 is estimated to be 2086, while the projected number for 2030 is estimated to be 2637. The literature has predominantly focused on disease markers and diagnostic methods, severity and effects of the disease, immunity and inflammation, effects of the disease in neonates and the neonatal period, and treatment and care. According to trend analysis results, recent focus in sepsis research includes a broad spectrum of investigations such as mortality rates, prognostic determinants, diagnostic methods, biomarkers, epidemiological insights, critical care strategies, infections, treatment outcomes, emergency department scenarios, pediatric assessments, and antibiotic interventions.


Assuntos
Sepse , Choque Séptico , Recém-Nascido , Humanos , Criança , Bibliometria , França , Publicações , Sepse/terapia
16.
Int J Mol Sci ; 25(6)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38542094

RESUMO

This manuscript investigates the role of extracorporeal blood purification techniques in managing septic hyperinflammation, a critical aspect of sepsis characterized by an uncontrolled immune response leading to multiorgan dysfunction. We provide an overview of sepsis, focusing on the dynamics of immune response, the involvement of neutrophils, and the role of the endothelium in the disease's progression. It evaluates the effectiveness of various blood purification methods, including high-cut-off membranes, high-volume hemofiltration, adsorption techniques, and albumin dialysis, in removing cytokines and endotoxin and improving hemodynamic stability. Despite some very promising results, we conclude that the current evidence does not strongly support these techniques in significantly improving survival rates in septic patients, clearly underlining the need for further research.


Assuntos
Hemofiltração , Sepse , Choque Séptico , Humanos , Diálise Renal , Hemofiltração/métodos , Sepse/terapia , Citocinas , Adsorção
17.
Sci Rep ; 14(1): 6234, 2024 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-38485953

RESUMO

Sepsis is a heterogeneous syndrome and phenotypes have been proposed using clinical data. Less is known about the contribution of protein biomarkers to clinical sepsis phenotypes and their importance for treatment effects in randomized trials of resuscitation. The objective is to use both clinical and biomarker data in the Protocol-Based Care for Early Septic Shock (ProCESS) randomized trial to determine sepsis phenotypes and to test for heterogeneity of treatment effect by phenotype comparing usual care to protocolized early, goal-directed therapy(EGDT). In this secondary analysis of a subset of patients with biomarker sampling in the ProCESS trial (n = 543), we identified sepsis phenotypes prior to randomization using latent class analysis of 20 clinical and biomarker variables. Logistic regression was used to test for interaction between phenotype and treatment arm for 60-day inpatient mortality. Among 543 patients with severe sepsis or septic shock in the ProCESS trial, a 2-class model best fit the data (p = 0.01). Phenotype 1 (n = 66, 12%) had increased IL-6, ICAM, and total bilirubin and decreased platelets compared to phenotype 2 (n = 477, 88%, p < 0.01 for all). Phenotype 1 had greater 60-day inpatient mortality compared to Phenotype 2 (41% vs 16%; p < 0.01). Treatment with EGDT was associated with worse 60-day inpatient mortality compared to usual care (58% vs. 23%) in Phenotype 1 only (p-value for interaction = 0.05). The 60-day inpatient mortality was similar comparing EGDT to usual care in Phenotype 2 (16% vs. 17%). We identified 2 sepsis phenotypes using latent class analysis of clinical and protein biomarker data at randomization in the ProCESS trial. Phenotype 1 had increased inflammation, organ dysfunction and worse clinical outcomes compared to phenotype 2. Response to EGDT versus usual care differed by phenotype.


Assuntos
Sepse , Choque Séptico , Humanos , Choque Séptico/diagnóstico , Choque Séptico/terapia , Sepse/diagnóstico , Sepse/terapia , Biomarcadores , Fenótipo , Protocolos Clínicos
18.
ACS Nano ; 18(11): 7711-7738, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38427687

RESUMO

Sepsis, a common life-threatening clinical condition, continues to have high morbidity and mortality rates, despite advancements in management. In response, significant research efforts have been directed toward developing effective strategies. Within this scope, nanotechnology has emerged as a particularly promising field, attracting significant interest for its potential to enhance disease diagnosis and treatment. While several reviews have highlighted the use of nanoparticles in sepsis, comprehensive studies that summarize and analyze the hotspots and research trends are lacking. To identify and further promote the development of nanotechnology in sepsis, a bibliometric analysis was conducted on the relevant literature, assessing research trends and hotspots in the application of nanomaterials for sepsis. Next, a comprehensive review of the subjectively recognized research hotspots in sepsis, including nanotechnology-enhanced biosensors and nanoscale imaging for sepsis diagnostics, and nanoplatforms designed for antimicrobial, immunomodulatory, and detoxification strategies in sepsis therapy, is elucidated, while the potential side effects and toxicity risks of these nanomaterials were discussed. Particular attention is given to biomimetic nanoparticles, which mimic the biological functions of source cells like erythrocytes, immune cells, and platelets to evade immune responses and effectively deliver therapeutic agents, demonstrating substantial translational potential. Finally, current challenges and future perspectives of nanotechnology applications in sepsis with a view to maximizing their great potential in the research of translational medicine are also discussed.


Assuntos
Nanopartículas , Nanoestruturas , Sepse , Humanos , Nanotecnologia/métodos , Nanoestruturas/uso terapêutico , Nanopartículas/uso terapêutico , Diagnóstico por Imagem , Sepse/diagnóstico , Sepse/terapia
19.
Crit Care ; 28(1): 92, 2024 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515121

RESUMO

Acute kidney injury (AKI) often complicates sepsis and is associated with high morbidity and mortality. In recent years, several important clinical trials have improved our understanding of sepsis-associated AKI (SA-AKI) and impacted clinical care. Advances in sub-phenotyping of sepsis and AKI and clinical trial design offer unprecedented opportunities to fill gaps in knowledge and generate better evidence for improving the outcome of critically ill patients with SA-AKI. In this manuscript, we review the recent literature of clinical trials in sepsis with focus on studies that explore SA-AKI as a primary or secondary outcome. We discuss lessons learned and potential opportunities to improve the design of clinical trials and generate actionable evidence in future research. We specifically discuss the role of enrichment strategies to target populations that are most likely to derive benefit and the importance of patient-centered clinical trial endpoints and appropriate trial designs with the aim to provide guidance in designing future trials.


Assuntos
Injúria Renal Aguda , Sepse , Humanos , Injúria Renal Aguda/terapia , Injúria Renal Aguda/complicações , Estado Terminal/terapia , Sepse/complicações , Sepse/terapia , Ensaios Clínicos como Assunto
20.
Hosp Pediatr ; 14(4): 272-280, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38449428

RESUMO

BACKGROUND: Sepsis is responsible for 75 000 pediatric hospitalizations annually, with an associated mortality rate estimated between 11% and 19%. Evidence supports the use of timely fluid resuscitation and antibiotics to decrease morbidity and mortality. Our emergency department did not meet the timeliness goals for fluid and antibiotic administration suggested by the 2012 Surviving Sepsis Campaign. METHODS: In November 2018, we implemented a sepsis response team utilizing a scripted communication tool and a dedicated sepsis supply cart to address timeliness barriers. Performance was evaluated using statistical process control charts. We conducted observations to evaluate adherence to the new process. Our aim was to meet the Surviving Sepsis Campaign's timeliness goals for first fluid and antibiotic administration (20 and 60 minutes, respectively) within 8 months of our intervention. RESULTS: We observed sustained decreases in mean time to fluids. We also observed a shift in the proportion of patients receiving fluids within 20 minutes. No shifts were observed for timely antibiotic administration. CONCLUSIONS: The implementation of a dedicated emergency department sepsis response team with designated roles and responsibilities, directed communication, and easily accessible supplies can lead to improvements in the timeliness of fluid administration in the pediatric population.


Assuntos
Sepse , Humanos , Criança , Estudos Retrospectivos , Sepse/terapia , Sepse/tratamento farmacológico , Antibacterianos/uso terapêutico , Serviço Hospitalar de Emergência , Tempo para o Tratamento
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