Porous silica is an attractive biomaterial in many applications, including drug-delivery systems, bone-graft fillers and medical devices. The issue with porous silica biomaterials is the rate at which they resorb and the significant role played by interfacial chemistry on the host response in vivo. This paper explores the potential of diatom-biosilica as a model tool to assist in the task of mapping and quantifying the role of surface topography and chemical cues on cell fate. Diatoms are unicellular microalgae whose cell walls are composed of, amorphous nanopatterned biosilica that cannot be replicated synthetically. Their unique nanotopography has the potential to improve understanding of interface reactions between materials and cells. This study used Cyclotella meneghiniana as a test subject to assess cytotoxicity and pro-inflammatory reactions to diatom-biosilica. The results suggest that diatom-biosilica is non-cytotoxic to J774.2 macrophage cells, and supports cell proliferation and growth. The addition of amine and thiol linkers have shown a significant effect on cytotoxicity, growth and cytokine response, thus warranting further investigation into the interfacial effects of small chemical modifications to substrate surfaces. The overall findings suggest diatom-biosilica offers a unique platform for in-depth investigation of the role played by nanotopography and chemistry in biomedical applications.

Study objective

The transfusion of older packed RBCs may be harmful in critically ill patients. We seek to determine the association between packed RBC age and mortality among trauma patients requiring massive packed RBC transfusion.

Methods

We analyzed data from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios trial. Subjects in the parent trial included critically injured adult patients admitted to 1 of 12 North American Level I trauma centers who received at least 1 unit of packed RBCs and were predicted to require massive blood transfusion. The primary exposure was volume of packed RBC units transfused during the first 24 hours of hospitalization, stratified by packed RBC age category: 0 to 7 days, 8 to 14 days, 15 to 21 days, and greater than or equal to 22 days. The primary outcome was 24-hour mortality. We evaluated the association between transfused volume of each packed RBC age category and 24-hour survival, using random-effects logistic regression, adjusting for total packed RBC volume, patient age, sex, race, mechanism of injury, Injury Severity Score, Revised Trauma Score, clinical site, and trial treatment group.

Results

The 678 patients included in the analysis received a total of 8,830 packed RBC units. One hundred patients (14.8%) died within the first 24 hours. On multivariable analysis, the number of packed RBCs greater than or equal to 22 days old was independently associated with increased 24-hour mortality (adjusted odds ratio [OR] 1.05 per packed RBC unit; 95% confidence interval [CI] 1.01 to 1.08): OR 0.97 for 0 to 7 days old (95% CI 0.88 to 1.08), OR 1.04 for 8 to 14 days old (95% CI 0.99 to 1.09), and OR 1.02 for 15 to 21 days old (95% CI 0.98 to 1.06). Results of sensitivity analyses were similar only among patients who received greater than or equal to 10 packed RBC units.

Conclusion

Increasing quantities of older packed RBCs are associated with increased likelihood of 24-hour mortality in trauma patients receiving massive packed RBC transfusion (≥10 units), but not in those who receive fewer than 10 units.

Background

Altered coagulation function after trauma can contribute to development of venous thromboembolism (VTE). Severe trauma impairs coagulation function, but the trajectory for recovery is not known. We hypothesized that enhanced, early recovery of coagulation function increases VTE risk in severely injured trauma patients.

Study design

Secondary analysis was performed on data from the Pragmatic Randomized Optimal Platelet and Plasma Ratio (PROPPR) trial, excluding patients who died within 24 hours or were on pre-injury anticoagulants. Patient characteristics, adverse outcomes, and parameters of platelet function and coagulation (thromboelastography) were compared from admission to 72 hours between VTE (n = 83) and non-VTE (n = 475) patients. A p value < 0.05 indicates significance.

Results

Despite similar patient demographics, VTE patients exhibited hypercoagulable thromboelastography parameters and enhanced platelet function at admission (p < 0.05). Both groups exhibited hypocoagulable thromboelastography parameters, platelet dysfunction, and suppressed clot lysis (low clot lysis at 30 minutes) 2 hours after admission (p < 0.05). The VTE patients exhibited delayed coagulation recovery (a significant change compared with 2 hours) of K-value (48 vs 24 hours), α-angle (no recovery), maximum amplitude (24 vs 12 hours), and clot lysis at 30 minutes (48 vs 12 hours). Platelet function recovery mediated by arachidonic acid (72 vs 4 hours), ADP (72 vs 12 hours), and collagen (48 vs 12 hours) was delayed in VTE patients. The VTE patients had lower mortality (4% vs 13%; p < 0.05), but fewer hospital-free days (0 days [interquartile range 0 to 8 days] vs 10 days [interquartile range 0 to 20 days]; p < 0.05) and higher complication rates (p < 0.05).

Conclusions

Recovery from platelet dysfunction and coagulopathy after severe trauma were delayed in VTE patients. Suppressed clot lysis and compensatory mechanisms associated with altered coagulation that can potentiate VTE formation require additional investigation.