A University of Malta researcher, Dr Brendon Scicluna of the Department of Applied Biomedical Science, Faculty of Health Sciences, designed and spearheaded one of the studies and made significant contributions to the second, placing the University at the forefront of the global effort to bring precision medicine to the sickest patients in our hospitals.
For decades, developing new treatments for critical illnesses like sepsis, acute respiratory distress syndrome (ARDS), and trauma has been hampered by a major challenge, that is, although treated as single conditions, every patient's body responds differently. This biological diversity, known as heterogeneity, has been a primary barrier to progress. The two new studies tackle this problem head-on, providing a robust, unified way to classify patients into distinct cellular biological subtypes.
The first study, "A consensus blood transcriptomic framework for sepsis," led by Dr Scicluna, aggregated data from over 1,800 sepsis patients. Using a technique called blood transcriptomics, which measures the activity of thousands of genes to create a real-time snapshot of a patient's immune response, the team created a single, harmonized classification system. It identifies three " C onsensus T ranscriptomic S ubtypes" (CTSs) of sepsis, each with a unique molecular signature:
Crucially, the study delivered a stark warning. A reanalysis of a major randomized controlled trial revealed that patients assigned to the CTS2 subtype were actually harmed by corticosteroids , a common anti-inflammatory treatment for sepsis and other immune-related disorders. This finding underscores the urgent need to move beyond a one-size-fits-all approach.
The second study, "A consensus immune dysregulation framework for sepsis and critical illnesses," from the international SUBSPACE consortium to which Dr Scicluna contributed, complements this work perfectly. Analysing over 7,000 patient samples from 37 cohorts, this study identified two core patterns of immune dysregulation, one in myeloid cells (the immune system's first responders) and one in lymphoid cells (responsible for targeted immunity). Remarkably, the study found this same fundamental dysregulation was present not only in sepsis but also in patients with ARDS, trauma, and burns, suggesting shared biological mechanisms across multiple forms of critical illness.
The complementary findings from these two extensive studies offer a powerful new framework for understanding critical illness and, for the first time, provide a clear path forward for designing clinical trials that can finally deliver on the promise of precision medicine for the most vulnerable patients in the Intensive Therapy Unit (ITU).
“These studies are a powerful example of what happens when you combine clinical expertise with immunobiology and molecular profiling" concludes Dr Scicluna.
Dr Brendon Scicluna is a Principal Investigator leading the Translational Immunology and Infection lab at the University of Malta.
The research described in these publications was supported by funding from the European Society for Intensive Care Medicine, a University of Malta Research Excellence Award, and multiple grants from the Xjenza Malta Research Excellence Program. The work also received foundational support from the Center for Translational Molecular Medicine in the Netherlands.
Papers cited in this article:
A consensus blood transcriptomic framework for sepsis | Nature Medicine
A consensus immune dysregulation framework for sepsis and critical illnesses | Nature Medicine
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A consensus blood transcriptomic framework for sepsis
30-Sep-2025