Novel Diagnostics and Therapeutics in Sepsis

Leong, Kieran; Gaglani, Bhavita; Khanna, Ashish K.; McCurdy, Michael T.

doi:10.3390/biomedicines9030311

Cited by 11 publications

(8 citation statements)

References 157 publications

(229 reference statements)

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“…Some biomarkers, such as CRP and PCT, are widely used as acute‐phase reactants in critically ill patients but have limited prognostic value for sepsis (Leong et al, 2021; Trzeciak et al, 2020). The nurses in the study classified the increase in CRP level (92.8%) and PCT level (62.7%) as early warning findings of sepsis.…”

Section: Discussionmentioning

confidence: 99%

Intensive care nurses’ awareness of identification of early sepsis findings

Birge

Aydın

Çamdeviren

2021

Journal of Clinical Nursing

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Aim To determine intensive care nurses’ awareness of identification of early sepsis findings. Background The incidence of sepsis is increasing in intensive care units, and if not identified early, it increases morbidity, mortality and cost of care. Intervention within one hour after the diagnosis of sepsis increases survival. Nurses’ ability to identify early findings of sepsis affects the time of diagnosis of sepsis. Design The study used a cross‐sectional design. Methods The sample of the study consisted of 544 nurses working in adult intensive care units of hospitals in Turkey. The study data were collected online between 11 January–8 April 2021 using the snowball method. Data were statically analysed. All procedures of the study adhered to the STROBE guidelines. Results The nurses who had been working for 11 years or more, had worked with a patient diagnosed with sepsis in the last month and used a measurement tool in the diagnosis thought that it was significantly easier to determine the early warning findings of sepsis. In the study, the majority of nurses correctly identified the early findings of sepsis, but the rates of the correct responses to the variables of lactate >2 mM, leucopenia and hypothermia were low. Female gender, having a graduate degree, unit type, total work experience, having received training on sepsis and working with a patient diagnosed with sepsis in the last month made a significant difference in determining the early warning findings of sepsis accurately. Conclusions Nurses had a good rate of identifying early sepsis findings. Yet, they could not distinguish between early sepsis and late sepsis findings. Relevance to clinical practice The results of the study can support nursing practices in the diagnostic process by considering the factors affecting nurses’ ability to distinguish early sepsis findings from late sepsis findings and to identify them correctly.

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Section: Discussionmentioning

confidence: 99%

Intensive care nurses’ awareness of identification of early sepsis findings

Birge

Aydın

Çamdeviren

2021

Journal of Clinical Nursing

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“…In a minipig model, designed to reflect human physiology more accurately than rodent models [ 65 ], researchers induced peritonitis and then either treated or did not treat the animals with LR12. After peritonitis, the mean arterial blood pressure decreased rapidly despite volume resuscitation, and the researchers treated the pigs with a norepinephrine infusion, similarly to septic shock therapy [ 66 ].…”

Section: Trem-1 and Its Ligands In The Inflammatory Statementioning

confidence: 99%

“…The overall baseline median plasma sTREM-1 level was 433 pg/mL (range: 154–1960 pg/mL). In a subgroup analysis, patients with high levels of sTREM-1 treated with nangibotide had decreased SOFA scores after treatment [ 12 , 14 , 65 ].…”

Section: Trem-1 and Its Ligands In The Inflammatory Statementioning

confidence: 99%

Triggering receptor expressed on myeloid cells-1 in sepsis, and current insights into clinical studies

Theobald,

Schmitt,

Middel

et al. 2024

Crit Care

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Triggering receptor expressed on myeloid cells-1 (TREM-1) is a pattern recognition receptor and plays a critical role in the immune response. TREM-1 activation leads to the production and release of proinflammatory cytokines, chemokines, as well as its own expression and circulating levels of the cleaved soluble extracellular portion of TREM-1 (sTREM-1). Because patients with sepsis and septic shock show elevated sTREM-1 levels, TREM-1 has attracted attention as an important contributor to the inadequate immune response in this often-deadly condition. Since 2001, when the first blockade of TREM-1 in sepsis was performed, many potential TREM-1 inhibitors have been established in animal models. However, only one of them, nangibotide, has entered clinical trials, which have yielded promising data for future treatment of sepsis, septic shock, and other inflammatory disease such as COVID-19. This review discusses the TREM-1 pathway and important ligands, and highlights the development of novel inhibitors as well as their clinical potential for targeted treatment of various inflammatory conditions.

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“…LR12 is the first TREM-1 inhibitor to have reached the clinical stage. It is currently being studied in Phase 2 clinical trials of sepsis, COVID-19, and acute myocardial infarction under the name Inotrem (nangibotide) ( 16 , 82 , 83 , 96 – 98 ). Nangibotide is an immune modulator targeting the inflammatory response amplification maintained by TREM-1 ( 82 ).…”

Section: Trem-1 Blockade As a Therapeutic Approachmentioning

confidence: 99%

“…Treatment with nangibotide, however, was associated with a decrease in the serum levels of IL-6 ( 82 ). In a subgroup analysis, patients with high sTREM-1 treated with nangibotide had decreased SOFA scores after treatment ( 82 , 98 ), suggesting that sTREM-1 could be a potential biomarker to predict which septic patients respond to nangibotide. A pivotal Phase 2b trial, looking at the efficacy, safety, and tolerability of nangibotide in patients with septic shock is currently underway ( 16 , 97 ).…”

Section: Trem-1 Blockade As a Therapeutic Approachmentioning

confidence: 99%

TREM-1 Modulation Strategies for Sepsis

Siskind

Wang²

2022

Front. Immunol.

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The triggering receptor expressed on myeloid cells-1 (TREM-1) is a pattern recognition receptor, which can be upregulated in inflammatory diseases as an amplifier of immune responses. Once activated, TREM-1 induces the production and release of pro-inflammatory cytokines and chemokines, in addition to increasing its own expression and circulating levels of the cleaved soluble extracellular portion of TREM-1 (sTREM-1). This amplification of the inflammatory response by TREM-1 has now been considered as a critical contributor to the dysregulated immune responses in sepsis. Studies have shown that in septic patients there is an elevated expression of TREM-1 on immune cells and increased circulating levels of sTREM-1, associated with increased mortality. As a result, a considerable effort has been made towards identifying endogenous ligands of TREM-1 and developing TREM-1 inhibitory peptides to attenuate the exacerbated inflammatory response in sepsis. TREM-1 modulation has proven a promising strategy for the development of therapeutic agents to treat sepsis. Therefore, this review encompasses the ligands investigated as activators of TREM-1 thus far and highlights the development and efficacy of novel inhibitors for the treatment of sepsis and septic shock.

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Novel Diagnostics and Therapeutics in Sepsis

Cited by 11 publications

References 157 publications

Intensive care nurses’ awareness of identification of early sepsis findings

Intensive care nurses’ awareness of identification of early sepsis findings

Triggering receptor expressed on myeloid cells-1 in sepsis, and current insights into clinical studies

TREM-1 Modulation Strategies for Sepsis

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