Biology subjects

Scicluna, B.

Publications and source records attributed to Scicluna, B..

3 recordsLinked to original sources

bioRxiv2024

International multi-cohort analysis identifies novel framework for quantifying immune dysregulation in critical illness: results of the SUBSPACE consortium

Progress in the management of critical care syndromes such as sepsis, Acute Respiratory Distress Syndrome (ARDS), and trauma has slowed over the last two decades, limited by the inherent heterogeneity within syndromic illnesses. Numerous immune endotypes have been proposed in sepsis and critical care, however the overlap of the endotypes is unclear, limiting clinical translation. The SUBSPACE consortium is an international consortium that aims to advance precision medicine through the sharing of transcriptomic data. By evaluating the overlap of existing immune endotypes in sepsis across over 6,000 samples, we developed cell-type specific signatures to quantify dysregulation in these immune compartments. Myeloid and lymphoid dysregulation were associated with disease severity and mortality across all cohorts. This dysregulation was not only observed in sepsis but also in ARDS, trauma, and burn patients, indicating a conserved mechanism across various critical illness syndromes. Moreover, analysis of randomized controlled trial data revealed that myeloid and lymphoid dysregulation is linked to differential mortality in patients treated with anakinra or corticosteroids, underscoring its prognostic and therapeutic significance. In conclusion, this novel immunology-based framework for quantifying cellular compartment dysregulation offers a valuable tool for prognosis and therapeutic decision-making in critical illness.

immunology↗

bioRxiv2018

A pilot study of a novel molecular host response assay to diagnose infection in patients after high-risk gastro-intestinal surgery

AimSeptiCyte LAB measures the expression of four host-response RNAs in blood to distinguish sepsis from sterile inflammation. Sequential monitoring of this assay may have diagnostic utility in patients at high risk for postoperative infectious complications.\n\nMethodsIn this pilot study we studied esophagectomy patients who had developed a complication within 30 days following surgery as well as a random sample of 100 uncomplicated postoperative patients. PAXgene blood samples were collected postoperatively and whenever a complication occurred. SeptiCyte scores (ranging 0-10 with increasing likelihood of infection) were compared to post-hoc physician adjudication of infection likelihood using strict definitions.\n\nResultsAmong 370 esophagectomy patients, 120 (32%) subjects developed a complication requiring ICU (re)admission, 63 (53%) of whom could be analyzed. Immediate postoperative SeptiCyte LAB scores were highly variable, yet similar for patients having a complicated and uncomplicated postoperative course (median score of 2.4 (IQR 1.6-3.3) versus 2.2 (IQR 1.3-3), respectively). Scores increased as complications developed, but this rise was higher for 34 subjects having confirmed infection (median difference 4.7 (IQR 4.1-5.8)) then for 12 subjects with a non-infectious complication (2.1 (IQR 0.4-3.6); p<0.0001). When 17 cases with undetermined infectious status were excluded, addition of SeptiCyte LAB to CRP resulted in improved diagnostic discrimination (AUC 0.88 (95%CI 0.77-0.99)) compared to CRP alone (AUC 0.76 (95%CI 0.61-0.91); p=0.04).\n\nConclusionsSequential measurement of SeptiCyte LAB may have clinical utility in surgical patients at high risk of postoperative infection, but its diagnostic performance in this setting needs to be further evaluated.

epidemiology↗

bioRxiv2017

Validation Of A Novel Molecular Host Response Assay To Diagnose Infection In Hospitalized Patients Admitted To The ICU With Acute Respiratory Failure

PurposeThe discrimination between infectious and non-infectious causes of acute respiratory failure (ARF) in hospitalized patients admitted to the intensive care unit (ICU) is difficult. Using a novel diagnostic test measuring the expression of four RNA biomarkers in blood (SeptiCyte LAB) we aimed to distinguish between infection and inflammation in this setting.\n\nMethodsWe enrolled hospitalized patients with ARF requiring prompt intubation in the ICU from 2011 to 2013. We excluded patients having an established infection diagnosis or an evidently non-infectious reason for intubation. Blood samples were collected upon ICU admission. Test results were categorized into four probability bands (with higher bands indicating a higher probability of infection) and compared with the plausibility of infection as rated by post-hoc assessment using predefined definitions.\n\nResultsOf 467 included patients, 373 (80%) were treated for a suspected infection at admission. Plausibility of infection was classified as ruled-out, undetermined, or confirmed in 41 (11%), 135 (36%), and 197 (53%) of these, respectively. Overall, the pre-test probability of infection was 42%. Test results correlated with the plausibility of infection (Spearmans rho 0.332; p<0.001). After exclusion of undetermined cases, positive predictive values were 29%, 54%, and 76% for probability bands 2, 3, and 4, respectively, whereas the negative predictive value for band 1 was 76%. However, SeptiCyte LAB did not outperform CRP when comparing diagnostic discrimination (AUC 0.731; 95%CI 0.677-0.786 vs. 0.727; 95%CI 0.666-0.788).\n\nConclusionIn a setting of hospitalized patients admitted to the ICU with ARF, the diagnostic value of SeptiCyte LAB seems limited.

epidemiology↗