Background: Prompt recognition of sepsis is critical to improving patients’ outcomes. We compared the performance of NEWS and qSOFA scores as sepsis detection tools in patients admitted to the emergency department (ED) with suspicion of sepsis. Methodology: A single-center 12-month retrospective study comparing NEWS using the recommended cut-off of ≥5 and qSOFA as sepsis screening tools in a cohort of patients transported by emergency medical services (EMS) to the Lausanne University Hospital (LUH). We used the Sepsis-3 consensus definition. The primary study endpoint was the detection of sepsis. Secondary endpoints were ICU admission and 28-day all-cause mortality. Results: Among 886 patients admitted to ED by EMS for suspected infection, 556 (63%) had a complete set of vital parameters panel enabling the calculation of NEWS and qSOFA scores, of whom 300 (54%) had sepsis. For the detection of sepsis, the sensitivity of NEWS > 5 was 86% and that of qSOFA ≥ 2 was 34%. Likewise, the sensitivities of NEWS ≥ 5 for predicting ICU admission and 28-day mortality were higher than those of qSOFA ≥ 2 (82% versus 33% and 88% versus 37%). Conversely, the specificity of qSOFA ≥ 2 for sepsis detection was higher than that of NEWS ≥ 5 (90% versus 55%). The negative predictive value of NEWS > 5 was higher than that of qSOFA ≥ 2 (77% versus 54%), while the positive predictive value of qSOFA ≥ 2 was higher than that of NEWS ≥ 5 (80% versus 69%). Finally, the accuracy of NEWS ≥ 5 was higher than that of qSOFA ≥ 2 (72% versus 60%). Conclusions: The sensitivity of NEWS ≥ 5 was superior to that of qSOFA ≥ 2 to identify patients with sepsis in the ED and predict ICU admission and 28-day mortality. In contrast, qSOFA ≥ 2 had higher specificity and positive predictive values than NEWS ≥ 5 for these three endpoints.
21 November 2024 in Journal for ImmunoTherapy of Cancer
Background Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. CRC deaths can be reduced with prevention and early diagnosis. Circulating tumor DNA-based liquid biopsies, are emerging tools for cancer detection. However, the tumor-signal-dependent nature of this approach results in low sensitivity in precancerous and early CRC stages. Here we propose the host immune response to the onset of cancer as an alternative approach for early detection of CRC. Methods We perform whole transcriptome analysis of peripheral blood mononuclear cells (PBMCs) isolated from individuals with CRC, precancerous lesions or negative colonoscopy in two independent cohorts using next-generation sequencing. Results We discover and validate novel early CRC RNA biomarkers. Taking into account, and adjusting for, the sensitivity of PBMCs transcriptomes to processing times, we report distinct transcriptomic changes in the periphery related to specific CRC stages. Activation of innate immunity is already detectable in the peripheral blood of individuals with pre-malignant advanced adenomas. This immune response is followed by signs of transient B-cell activation and sustained inhibition of T-cell responses along CRC progression, whereby at late stages, protumoral myeloid cells, wound healing and coagulation processes prevail. Moreover, some biomarkers show similar dysregulation in tumors and are implicated in known pathways of CRC pathophysiology. Conclusions The strong systemic immune modulation triggered during CRC progression leads to previously unnoticed alterations detectable in PBMCs, paving the way for the development of an early CRC screening blood test, incorporating 226 validated biomarkers identified through immunotranscriptomics.