Clara Vigneron

Sepsis and cancer share a number of pathophysiological features, and both result from the inability of the host's immune system to cope with the initial insult (tissue invasion by pathogens and malignant cell transformation, respectively). The common coexistence of both disorders and the profound related alterations in immune homeostasis raise the question of their mutual impact on each other's course. This translational review aims to discuss the interactions between cancer and sepsis supported by clinical data and the translation to experimental models. The dramatic improvement in cancer has come at a cost of increased risks of life-threatening infectious complications. Investigating the long-term outcomes of sepsis survivors has revealed an unexpected susceptibility to cancer long after discharge from the ICU. Nonetheless, it is noteworthy that an acute septic episode may harbor antitumoral properties under particular circumstances. Relevant double-hit animal models have provided clues to whether and how bacterial sepsis may impact malignant tumor growth. In sequential sepsis-then-cancer models, postseptic mice exhibited accelerated tumor growth. When using reverse cancer-then-sepsis models, bacterial sepsis applied to mice with cancer conversely resulted in inhibition or even regression of tumor growth. Experimental models thus highlight dual effects of sepsis on tumor growth, mostly depending on the sequence of insults, and allow deciphering the immune mechanisms and their relation with microorganisms.

PURPOSE: /L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. METHODS: We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. RESULTS: We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4-46.1) had thrombocytopenia; 23.4% (20-26) had thrombocytopenia at ICU admission, and 19.8% (17.6-22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19-2.42). CONCLUSION: Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.

BACKGROUND: Major therapeutic advances including immunotherapy and targeted therapies have been changing the face of oncology and resulted in improved prognosis as well as in new toxic complications. The aim of this study is to appraise the trends in intensive care unit (ICU) admissions and outcomes of critically ill patients with solid malignancies. We performed a retrospective single-centre study over a 12-year period (2007-2018) including adult patients with solid malignancies requiring unplanned ICU admission. Admission patterns were classified as: (i) specific if directly related to the underlying cancer; (ii) non-specific; (iii) drug-related or procedural adverse events. RESULTS: 1525 patients were analysed. Lung and gastro-intestinal tract accounted for the two main tumour sites. The proportion of patients with metastatic diseases increased from 48.6% in 2007-2008 to 60.2% in 2017-2018 (p = 0.004). Critical conditions were increasingly related to drug- or procedure-related adverse events, from 8.8% of ICU admissions in 2007-2008 to 16% in 2017-2018 (p = 0.01). The crude severity of critical illness at ICU admission did not change over time. The ICU survival rate was 77.4%, without any significant changes over the study period. Among the 1279 patients with complete follow-up, the 1-year survival rate was 33.2%. Independent determinants of ICU mortality were metastatic disease, cancer in progression under treatment, admission for specific complications and the extent of organ failures (invasive and non-invasive ventilation, inotropes/vasopressors, renal replacement therapy and SOFA score). One-year mortality in ICU-survivors was independently associated with lung cancer, metastatic disease, cancer in progression under treatment, admission for specific complications and decision to forgo life-sustaining therapies. CONCLUSION: Advances in the management and the prognosis of solid malignancies substantially modified the ICU admission patterns of cancer patients. Despite underlying advanced and often metastatic malignancies, encouraging short-term and long-term outcomes should help changing the dismal perception of critically ill cancer patients.

OBJECTIVES: Ventilator-associated pneumonia is frequent in ICUs. Extended-spectrum β-lactamase-producing Enterobacteriaceae are difficult-to-treat pathogens likely to cause ventilator-associated pneumonia. We sought to assess the interest of screening for extended-spectrum β-lactamase-producing Enterobacteriaceae rectal carriage as a way to predict their involvement in ventilator-associated pneumonia. DESIGN: A retrospective cohort study of patients with suspected ventilator-associated pneumonia in a medical ICU was conducted. PATIENTS: Every patient admitted between January 2006 and August 2013 was eligible if subjected to mechanical ventilation for more than 48 hours. Each patient with suspected ventilator-associated pneumonia was included in the cohort. Active surveillance culture for extended-spectrum β-lactamase-producing Enterobacteriaceae detection was routinely performed in all patients at admission and then weekly throughout the study period. Extended-spectrum β-lactamase colonization was defined by the isolation of at least one extended-spectrum β-lactamase-producing Enterobacteriaceae from rectal swab culture. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 587 patients with suspected ventilator-associated pneumonia, 40 (6.8%) were colonized with extended-spectrum β-lactamase-producing Enterobacteriaceae prior to the development of pneumonia. Over the study period, 20 patients (3.4%) had ventilator-associated pneumonia caused by extended-spectrum β-lactamase-producing Enterobacteriaceae; of whom, 17 were previously detected as being colonized with extended-spectrum β-lactamase-producing Enterobacteriaceae. Sensitivity and specificity of prior extended-spectrum β-lactamase-producing Enterobacteriaceae colonization as a predictor of extended-spectrum β-lactamase-producing Enterobacteriaceae involvement in ventilator-associated pneumonia were 85.0% and 95.7%, respectively. The positive and negative predictive values were 41.5% and 99.4%, respectively. The positive likelihood ratio was 19.8. CONCLUSIONS: Screening for extended-spectrum β-lactamase-producing Enterobacteriaceae digestive colonization by weekly active surveillance cultures could reliably exclude the risk of the involvement of such pathogens in patients with ventilator-associated pneumonia in low-prevalence area.