A stratification strategy to predict secondary infection in critical illness-induced immune dysfunction: the REALIST score

International audienceBackground Although multiple individual immune parameters have been demonstrated to predict the occurrence of secondary infection after critical illness, significant questions remain with regards to the selection, timing and clinical utility of such immune monitoring tests. Research question As a sub-study of the REALISM study, the REALIST score was developed as a pragmatic approach to help clinicians better identify and stratify patients at high risk for secondary infection, using a simple set of relatively available and technically robust biomarkers. Study design and methods This is a sub-study of a single-centre prospective cohort study of immune profiling in critically ill adults admitted after severe trauma, major surgery or sepsis/septic shock. For the REALIST score, five immune parameters were pre-emptively selected based on their clinical applicability and technical robustness. Predictive power of different parameters and combinations of parameters was assessed. The main outcome of interest was the occurrence of secondary infection within 30 days. Results After excluding statistically redundant and poorly predictive parameters, three parameters remained in the REALIST score: mHLA-DR, percentage of immature (CD10 − CD16 − ) neutrophils and serum IL-10 level. In the cohort of interest ( n = 189), incidence of secondary infection at day 30 increased from 8% for patients with REALIST score of 0 to 46% in patients with a score of 3 abnormal parameters, measured ad D5–7. When adjusted for a priori identified clinical risk factors for secondary infection (SOFA score and invasive mechanical ventilation at D5–7), a higher REALIST score was independently associated with increased risk of secondary infection (42 events (22.2%), adjusted HR 3.22 (1.09–9.50), p = 0.034) and mortality (10 events (5.3%), p = 0.001). Interpretation We derived and presented the REALIST score, a simple and pragmatic stratification strategy which provides clinicians with a clear assessment of the immune status of their patients. This new tool could help optimize care of these individuals and could contribute in designing future trials of immune stimulation strategies

Immune Profiling Panel Gene Set Identifies Critically Ill Patients With Low Monocyte Human Leukocyte Antigen-DR Expression: Preliminary Results From the REAnimation Low Immune Status Marker (REALISM) Study

OBJECTIVES: There is a crucial unmet need for biomarker-guided diagnostic andprognostic enrichment in clinical trials evaluating immune modulating therapies incritically ill patients. Low monocyte expression of human leukocyte antigen-DR(mHLA-DR), considered as a reference surrogate to identify immunosuppressedpatients, has been proposed for patient stratification in immunostimulationapproaches. However, its widespread use in clinic has been somewhat hamperedby technical constraints inherent to flow cytometry technology. The objective ofthe present study was to evaluate the ability of a prototype multiplex polymerasechain reaction tool (immune profiling panel [IPP]) to identify immunosuppressedICU patients characterized by a low mHLA-DR expression.DESIGN: Retrospective observational cohort study.SETTING: Adult ICU in a University Hospital, Lyon, France.PATIENTS: Critically ill patients with various etiologies enrolled in the REAnimationLow Immune Status Marker study (NCT02638779).INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: mHLA-DR and IPP data were obtained from 1,731 blood samples collected from critically ill patients with various etiologies and healthy volunteers. A partial least square regression model combining the expression levels of IPP markers was trained and used for the identification of samples from patients presenting with evidence of immunosuppression, defined here as mHLADR less than 8,000 antibodies bound per cell (AB/C). The IPP gene set had an area under the receiver operating characteristic curve (AUC) of 0.86 (95% CI 0.83–0.89) for the identification of immunosuppressed patients. In addition, when applied to the 123 patients still in the ICU at days 5–7 after admission, IPP similarly enriched the number of patients with ICU-acquired infections in the immunosuppressed group (26%), in comparison with low mHLA-DR (22%).CONCLUSIONS: This study reports on the potential of the IPP gene set to identify ICU patients presenting with mHLA-DR less than 8,000 AB/C. Upon further optimizationand validation, this molecular tool may help in the stratification of patients that could benefit from immunostimulation in the context of personalized medicine

Recent advances in biodegradable metals for medical sutures: A critical review

Sutures that biodegrade and dissolve over a period of several weeks are in great demand to stitch wounds and surgical incisions. These new materials are receiving increased acceptance across surgical procedures whenever permanent sutures and long‐term care are not needed. Unfortunately, both inflammatory responses and adverse local tissue reactions in the close‐to‐stitching environment are often reported for biodegradable polymeric sutures currently used by the medical community. While bioabsorbable metals are predominantly investigated and tested for vascular stent or osteosynthesis applications, they also appear to possess adequate bio­compatibility, mechanical properties, and corrosion stability to replace biodegradable polymeric sutures. In this Review, biodegradable alloys made of iron, magnesium, and zinc are critically evaluated as potential materials for the manufacturing of soft and hard tissue sutures. In the case of soft tissue closing and stitching, these metals have to compete against currently available degradable polymers. In the case of hard tissue closing and stitching, biodegradable sternal wires could replace the permanent sutures made of stainless steel or titanium alloys. This Review discusses the specific materials and degradation properties required by all suture materials, summarizes current suture testing protocols and provides a well‐grounded direction for the potential future development of biodegradable metal based sutures