Sepsis-Associated Outcomes in Critically Ill Patients with Malignancies

Torres, Viviane Bogado Leite; Azevedo, Luciano C. P.; Silva, Ulysses V. A.; Caruso, Pedro; Torelly, André P.; Silva, Eliezer; Carvalho, Frederico Bruzzi de; Vianna, Arthur; Souza, Patterson P. de; Godoy, Michele Maria Gonçalves de; Azevedo, José Raimundo A. de; Spector, Nelson; Bozza, Fernando A.; Salluh, Jorge I.; Soares, Márcio

doi:10.1513/annalsats.201501-046oc

Cited by 63 publications

(69 citation statements)

References 31 publications

(40 reference statements)

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“…Different infections will impact the host differentially, and even within a single organism, different virulence factors will induce distinct responses. The host response is equally variable, and different genetic, epigenetic, and cellular/subcellular factors lead patients to respond very differently to the identical therapy [124][125][126][127][128][129][130].…”

Section: Which Is the Epidemiology Of Sepsis Susceptibility And Respomentioning

confidence: 99%

Surviving sepsis campaign: research priorities for sepsis and septic shock

et al. 2018

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Objective: To identify research priorities in the management, epidemiology, outcome and underlying causes of sepsis and septic shock.Design: A consensus committee of 16 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine was convened at the annual meetings of both societies. Subgroups had teleconference and electronic-based discussion. The entire committee iteratively developed the entire document and recommendations.Methods: Each committee member independently gave their top five priorities for sepsis research. A total of 88 suggestions (ESM 1 -supplemental table 1) were grouped into categories by the committee co-chairs, leading to the formation of seven subgroups: infection, fluids and vasoactive agents, adjunctive therapy, administration/epidemiology, scoring/identification, post-intensive care unit, and basic/translational science. Each subgroup had teleconferences to go over each priority followed by formal voting within each subgroup. The entire committee also voted on top priorities across all subgroups except for basic/translational science. Results:The Surviving Sepsis Research Committee provides 26 priorities for sepsis and septic shock. Of these, the top six clinical priorities were identified and include the following questions: (1) can targeted/personalized/precision medicine approaches determine which therapies will work for which patients at which times?; (2) what are ideal endpoints for volume resuscitation and how should volume resuscitation be titrated?; (3) should rapid diagnostic tests be implemented in clinical practice?; (4) should empiric antibiotic combination therapy be used in sepsis or septic shock?; (5) what are the predictors of sepsis long-term morbidity and mortality?; and (6) what information identifies organ dysfunction?Conclusions: While the Surviving Sepsis Campaign guidelines give multiple recommendations on the treatment of sepsis, significant knowledge gaps remain, both in bedside issues directly applicable to clinicians, as well as understanding the fundamental mechanisms underlying the development and progression of sepsis. The priorities identified represent a roadmap for research in sepsis and septic shock.

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Section: Which Is the Epidemiology Of Sepsis Susceptibility And Respomentioning

confidence: 99%

Surviving sepsis campaign: research priorities for sepsis and septic shock

et al. 2018

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“…While frailty can be readily defined [41, 42], it is difficult to measure in the emergency setting, although attempted by several recent approximated measures [43–46]. In particular, patients with IAIs and pre-existing malignant disease have a particular high risk for a poor outcome [47, 48]. …”

Section: Which Patients Are At High Risk Of Failure?mentioning

confidence: 99%

Management of intra-abdominal infections: recommendations by the WSES 2016 consensus conference

et al. 2017

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This paper reports on the consensus conference on the management of intra-abdominal infections (IAIs) which was held on July 23, 2016, in Dublin, Ireland, as a part of the annual World Society of Emergency Surgery (WSES) meeting. This document covers all aspects of the management of IAIs. The Grading of Recommendations Assessment, Development and Evaluation recommendation is used, and this document represents the executive summary of the consensus conference findings.

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“…Patients with malignancy are at higher risk of developing sepsis than the general population . Particularly, it has been reported that the ICU and in‐hospital mortality rates for cancer patients with sepsis were 42% and 56%, respectively, frequencies that are much higher than immunocompetent patients . While the etiology behind the increased mortality observed in septic cancer patients compared to previously healthy patients is multifactorial (and likely includes exposure to various anticancer drugs), we previously demonstrated that the presence of cancer (in the absence of any other treatment) negatively impacts the mortality following sepsis, and is associated with phenotypic and functional changes in CD4 + T cell responses following sepsis .…”

Section: Introductionmentioning

confidence: 90%

“…that the ICU and in-hospital mortality rates for cancer patients with sepsis were 42% and 56%, respectively, frequencies that are much higher than immunocompetent patients. 6 While the etiology behind the increased mortality observed in septic cancer patients compared to previously healthy patients is multifactorial 7 (and likely includes exposure to various anticancer drugs), we previously demonstrated that the presence of cancer (in the absence of any other treatment) negatively impacts the mortality following sepsis, 8 and is associated with phenotypic and functional changes in CD4 + T cell responses following sepsis. 9 Specifically, cancer mice contained more resting memory and activated CD4 + effector cells, exhibited increased frequencies of PD-1 hi cells that failed to make any cytokines, and a distinct 2B4 hi BTLA hi LAG-3 hi population that secreted more TNF compared to previously healthy (PH) septic controls.…”

Section: Introductionmentioning

confidence: 99%

Preexisting malignancy abrogates the beneficial effects of CXCR4 blockade during sepsis

Zhang

Chihade

Xie

et al. 2020

Journal of Leukocyte Biology

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Patients with cancer are at an increased risk of developing and dying from sepsis. We previously reported that blockade of the chemokine receptor CXCR4 resulted in decreased CD4+ T cell exhaustion and improved survival in a model of polymicrobial sepsis in previously healthy mice. Here, we sought to determine whether CXCR4 blockade could improve mortality and immune dysregulation during sepsis complicated with malignancy. Results in animals inoculated with a lung cancer cell line and subjected to CLP 3 weeks later indicated that CXCR4 was up‐regulated on naïve and central memory T cells following sepsis. Of note, and in contrast to results in previously healthy mice, CXCR4 blockade failed to improve survival in cancer septic animals; instead, it actually significantly worsened survival. In the setting of cancer, CXCR4 blockade failed to result in T cell egress from the bone marrow, reverse lymphopenia in the spleen, or reverse T cell exhaustion. Mechanistically, elevated expression of CD69 on naïve T cells in the bone marrow of cancer septic animals was associated with their inability to egress from the bone marrow in the setting of CXCR4 blockade. In conclusion, these results illuminate the differential impact of CXCR4 blockade on sepsis pathophysiology in the setting of cancer and highlight the need for personalized therapy during sepsis.

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Sepsis-Associated Outcomes in Critically Ill Patients with Malignancies

Abstract: Sepsis is a common cause of critical illness in patients with cancer and remains associated with high mortality. Variables related to underlying malignancy, sepsis severity, and characteristics of infection are associated with a grim prognosis.

Cited by 63 publications

References 31 publications

Surviving sepsis campaign: research priorities for sepsis and septic shock

Surviving sepsis campaign: research priorities for sepsis and septic shock

Management of intra-abdominal infections: recommendations by the WSES 2016 consensus conference

Preexisting malignancy abrogates the beneficial effects of CXCR4 blockade during sepsis

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