Center for Translational Molecular Medicine, Netherlands.

Myocardial injury occurs in the majority of patients with sepsis and is independently associated with early-but not late-mortality, as well as postdischarge cardiovascular morbidity.

Purpose There is limited knowledge on how the source of infection impacts the host response to sepsis. We aimed to compare the host response in sepsis patients with a single, known source at admission (< 24 h) to the intensive care unit. Methods From the molecular diagnosis and risk stratification of sepsis (MARS) prospective cohort, we measured 16 plasma host response biomarkers reflective of key host response pathways in 621 sepsis patients. In a subgroup ( n = 335), blood leukocyte transcriptomes were compared between the sources. Differences in clinical patient profiles and survival were compared in the whole sepsis cohort ( n = 2019). Results The plasma biomarker cohort was categorized into sepsis originating from the respiratory tract ( n = 334, 53.8%), abdomen ( n = 159, 25.6%), urinary tract ( n = 44, 7.1%), cardiovascular ( n = 41, 6.6%), central nervous system (CNS) ( n = 18, 2.9%), or skin ( n = 25, 4%). This analysis revealed stronger inflammatory and cytokine responses, loss of vascular integrity and coagulation activation in abdominal sepsis relative to respiratory. Endothelial cell activation was prominent in urinary, cardiovascular and skin infections, while CNS infection was associated with the least host response aberrations. The leukocyte transcriptional response showed the largest overlap between abdominal and pulmonary infections (76% in common); notable differences between the sources were detected regarding hemostasis, cytokine signaling, innate and adaptive immune, and metabolic transcriptional pathways. After adjustment for confounders, the source of infection remained an independent contributor to 30-day mortality (unadjusted p = 0.001, adjusted p = 0.028). Conclusion Sepsis heterogeneity is partly explained by source-specific host response dysregulations and should be considered when selecting patients for trials testing immune modulatory drugs. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-021-06574-0.

Background Myocardial injury, as reflected by elevated cardiac troponin levels in plasma, is common in patients with community-acquired pneumonia (CAP), but its temporal dynamics and etiology remain unknown. Our aim was to determine the incidence of troponin release in patients with CAP and identify risk factors which may point to underlying etiologic mechanisms. MethodsWe included consecutive patients admitted with severe CAP to two intensive care units in the Netherlands between 2011 and 2015. High-sensitivity cardiac troponin I was measured daily during the first week. We used multivariable linear regression to identify variables associated with troponin release on admission, and mixed-effects regression to model the daily rise and fall of troponin levels over time.Results Among 200 eligible patients, 179 were included, yielding 792 observation days. A total of 152 (85%) patients developed raised troponin levels >26 ng/L. Baseline factors independently associated with troponin release included coronary artery disease (160% increase, 95% CI 7-529), smoking (304% increase, 95% CI 59-924), and higher APACHE IV score (2% increase, 95% CI 0.7-3.3), whereas Staphylococcus aureus as a causative pathogen was protective (67% reduction, 95% CI 9-88). Timedependent risk factors independently associated with daily increase in troponin concentrations included reduced platelet count (1.7% increase, 95% CI 0.1-3.4), tachycardia (1.6% increase, 95% CI 0.3-3), hypotension (5.1% increase, 95% CI 1-9.4) and dobutamine use (38.4% increase 95% CI 8.8-76).Conclusions Cardiac injury develops in a majority of patients with severe CAP. Myocardial oxygen supply-demand mismatch and activated coagulation are potential causes of this injury.

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