Reply to “Hyperoxemia in postsurgical sepsis/septic shock patients is associated with reduced mortality”

Martín-Fernández, Marta; Heredia-Rodríguez, María; Tamayo, Eduardo

doi:10.1186/s13054-022-04045-6

Cited by 5 publications

(6 citation statements)

References 5 publications

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“…Advances in supportive care have significantly improved the clinical outcomes of patients with sepsis, and new clinical trials are seeking further advantages over infusion, hemodynamic, and sedation therapies. 31 However, due to differences in the clinical definition of sepsis and the multifaceted manifestations observed during the clinical course, the inclusion criteria for patients with sepsis and the observed clinical end points varied over the course of the trial. 431 Some of the metrics of basic experiments do not seem to match the significance of clinical monitoring and cannot cover its impact on clinical efficacy, which is an inherent limitation of basic research.…”

Section: Sepsis-related Biologics: Preclinical Studies and Clinical T...mentioning

confidence: 99%

“…and their products can trigger a host immune response that is critical for maintaining and restoring homeostasis but can lead to tissue damage if excessive. 31 In practice, the greater the inflammatory response is, the stronger the cellular damage and thus the higher the risk of organ dysfunction. 18 At its onset, sepsis manifests as an overwhelming release of inflammatory mediators (cytokine storms) in response to infection.…”

Section: Inflammation and Immunementioning

confidence: 99%

“…The improper presence of microorganisms (bacteria, etc.) and their products can trigger a host immune response that is critical for maintaining and restoring homeostasis but can lead to tissue damage if excessive 31 . In practice, the greater the inflammatory response is, the stronger the cellular damage and thus the higher the risk of organ dysfunction 18 .…”

Section: Regulatory Mechanisms Involved In Sepsismentioning

confidence: 99%

“…Several large phase II and III trials are currently underway (Table 2). Advances in supportive care have significantly improved the clinical outcomes of patients with sepsis, and new clinical trials are seeking further advantages over infusion, hemodynamic, and sedation therapies 31 . However, due to differences in the clinical definition of sepsis and the multifaceted manifestations observed during the clinical course, the inclusion criteria for patients with sepsis and the observed clinical end points varied over the course of the trial 431 .…”

Section: Sepsis‐related Biologics: Preclinical Studies and Clinical T...mentioning

confidence: 99%

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The pathogenesis and potential therapeutic targets in sepsis

Zhang,

Jiang,

et al. 2023

MedComm

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Sepsis is defined as “a life‐threatening organ dysfunction caused by dysregulated host systemic inflammatory and immune response to infection.” At present, sepsis continues to pose a grave healthcare concern worldwide. Despite the use of supportive measures in treating traditional sepsis, such as intravenous fluids, vasoactive substances, and oxygen plus antibiotics to eradicate harmful pathogens, there is an ongoing increase in both the morbidity and mortality associated with sepsis during clinical interventions. Therefore, it is urgent to design specific pharmacologic agents for the treatment of sepsis and convert them into a novel targeted treatment strategy. Herein, we provide an overview of the molecular mechanisms that may be involved in sepsis, such as the inflammatory response, immune dysfunction, complement deactivation, mitochondrial damage, and endoplasmic reticulum stress. Additionally, we highlight important targets involved in sepsis‐related regulatory mechanisms, including GSDMD, HMGB1, STING, and SQSTM1, among others. We summarize the latest advancements in potential therapeutic drugs that specifically target these signaling pathways and paramount targets, covering both preclinical studies and clinical trials. In addition, this review provides a detailed description of the crosstalk and function between signaling pathways and vital targets, which provides more opportunities for the clinical development of new treatments for sepsis.

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Section: Sepsis-related Biologics: Preclinical Studies and Clinical T...mentioning

confidence: 99%

Section: Inflammation and Immunementioning

confidence: 99%

Section: Regulatory Mechanisms Involved In Sepsismentioning

confidence: 99%

Section: Sepsis‐related Biologics: Preclinical Studies and Clinical T...mentioning

confidence: 99%

See 2 more Smart Citations

The pathogenesis and potential therapeutic targets in sepsis

Zhang,

Jiang,

et al. 2023

MedComm

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“…Subgroup analyses of RCTs on conservative oxygen usage during mechanical ventilation reported conflicting results on the harmful effects of hyperoxia among patients with sepsis 15 16. Moreover, several post-hoc analyses targeting on the association between PaO 2 and mortality due to sepsis also showed various effects of hyperoxia from benefits to harms 17 18…”

Section: Introductionmentioning

confidence: 99%

Hyperoxia for sepsis and development of acute lung injury with increased mortality

Yamamoto,

Fujishima,

Yamakawa

et al. 2023

BMJ Open Resp Res

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BackgroundSupraphysiological oxygen administration causes unfavourable clinical outcomes in various diseases. This study aimed to determine whether hyperoxia would be associated with increased mortality in patients with severe infection.MethodsA post-hoc analysis of a nationwide multicentre prospective observational study on sepsis (SPICE Study) was conducted, including adult patients admitted to the intensive care unit with available arterial partial pressure of oxygen (PaO2) at the treatment initiation for severe infection. Hyperoxia was defined as a PaO2level of ≥300 mm Hg and in-hospital mortality was compared between patients with and without hyperoxia.ResultsOf the 563 patients eligible for the study, 49 had hyperoxia at treatment initiation for severe infection. The in-hospital all-cause mortality rates of patients with and without hyperoxia were 14 (29.2%) and 90 (17.6%), respectively. Inverse probability weighting analyses with propensity scores revealed the association between hyperoxia and increased in-hospital mortality rate (28.8% vs 18.8%; adjusted OR 1.75 (1.03 to 2.97); p=0.038), adjusting for patient demographics, comorbidities, site of infection, severity of infection, haemodynamic and respiratory status, laboratory data and location of patient at infection development. Acute lung injury developed more frequently in patients with hyperoxia on the following days after infection treatment, whereas sepsis-related mortality was comparable regardless of hyperoxia exposure.ConclusionHyperoxia with PaO2≥300 mm Hg at treatment initiation of severe infection was associated with an increased in-hospital mortality rate in patients requiring intensive care. The amount of oxygen to administer to patients with severe infection should be carefully determined.Trial registration numberUniversity Hospital Medical Information Network Clinical Trial Registry (UMIN000027452).

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Evaluation of Platelet Distribution Width as an Early Predictor of Acute Kidney Injury in Extensive Burn Patients

Jiang,

Zhang,

Zhang

et al. 2023

Emergency Medicine International

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Background. The extensive burns devastate trauma. The research was designed to analyse the predictive value of early platelet (PLT) indices on the development of acute kidney injury (AKI) after severe burns. Methods and Results. 186 patients with extensive burns (burn area ≥30%) were eventually involved. Multivariate analyses pointed out that platelet distribution width (PDW) in the first 24 h after admission was an independent risk factor for AKI, severe AKI, and RRT requirement in patients with severe burns, and AKI risk showed an increase of 30.9% per increase of 1% in PDW (OR = 1.309, CI, 1.075–1.594, and P = 0.007). It was found that the area under the ROC curve (AUC) of PDW predicting AKI was 0.735 and that the AUC value was 0.81 for AKI after combining PDW and blood urea nitrogen (BUN). Based on the cut-off value PDW = 17.7%, patients were divided into high- (PDW ≥17.7%) and low-risk (PDW <17.7%) groups. In the KM analysis, there was a higher cumulative incidence of AKI if patients were in a high-risk group (in 30 days); and the stages of AKI showed a linear upward trend (chi-square test for linear trend P < 0.001 ) as there was an increase in the risk level. Conclusion. The PDW level in the early stage serves as an important risk factor for AKI, severe AKI, and RRT requirement in extensive burns. When PDW >17.7%, burn patients are not only at a higher risk for AKI but may also have higher AKI severity. Due to low cost and wide availability, PDW has the potential to be the tool that can predict AKI in extensive burn patients.

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Reply to “Hyperoxemia in postsurgical sepsis/septic shock patients is associated with reduced mortality”

Cited by 5 publications

References 5 publications

The pathogenesis and potential therapeutic targets in sepsis

The pathogenesis and potential therapeutic targets in sepsis

Hyperoxia for sepsis and development of acute lung injury with increased mortality

Evaluation of Platelet Distribution Width as an Early Predictor of Acute Kidney Injury in Extensive Burn Patients

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