Clinical Assays in Sepsis: Prognosis, Diagnosis, Outcomes, and the Genetic Basis of Sepsis

Sepsis is the most widespread medical disorder of the intensive care unit (ICU) and the most common cause of death in hospitalized patients. Several endothelium-related molecules have been investigated as potential biomarkers for early diagnosis and/or prognosis of sepsis, providing different results depending on study designs. Therefore, it seems that we are still far from the right combination of sepsis markers to be used in clinical practice. It is more probable that a panel of diverse biomarkers will be more efficient in clinical practice. More recently, the potential use of genetic biomarkers for prognostic purposes started emerging for sepsis, in the form of genome-wide association studies. The successful use of modern molecular diagnostics could enable rapid identification of particularly susceptible or less susceptible individuals, leading to tailored therapeutic treatments

Prognostic Value of Bone Formation and Resorption Proteins in Heterotopic Ossification in Critically-Ill Patients. A Single-Centre Study

Introduction: A potential complication in critically ill patients is the formation of bone in soft tissues, termed heterotopic ossification. The exact pathogenetic mechanisms are still undetermined. Bone morphogenetic proteins induce bone formation, while signalling through the receptor activator of nuclear factor kappa-B (RANK) and its ligand (RANKL), regulates osteoclast formation, activation, and survival in normal bone modelling and remodelling. Osteoprotegerin protects bone from excessive bone loss by blocking RANKL from binding to RANK. Aim: The study aimed to investigate these molecules as potential prognostic biomarkers of heterotopic ossification development in critically ill patients. Materials and Methods: In this prospective observational study, BMP-2, RANKL, and osteoprotegerin were measured by ELISA in twenty-eight critically-ill, initially non-septic patients, on admission to an ICU, seven days post-admission, and thirty days after ICU discharge. Results: In the critically-ill cohort, nine of the twenty-eight patients developed heterotopic ossification up to the 30-day follow-up time-point. The patients who developed heterotopic ossification exhibited significantly reduced BMP-2 and RANKL levels on ICU admission, compared to patients who did not; Osteoprotegerin readings were similar in both groups. Conclusions: Critically-ill patients who will subsequently develop heterotopic ossification, have significantly lower BMP-2 and RANKL levels at the time of ICU admission, suggesting that these proteins may be useful as prognostic markers for this debilitating condition