Effect of Geriatric-Specific Trauma Triage Criteria on Outcomes in Injured Older Adults: A Statewide Retrospective Cohort Study.

OBJECTIVES: To evaluate the effect on outcomes of the Ohio Department of Public Safety statewide geriatric triage criteria, established in 2009 for emergency medical services (EMS) to use for injured individuals aged 70 and older. DESIGN: Retrospective cohort study of the Ohio Trauma Registry. SETTING: All hospitals in Ohio. PARTICIPANTS: Individuals aged 70 and older in the Ohio Trauma Registry from January 2006 through December 2011, 3 years before and 3 years after criteria adoption (N = 34,499). MEASUREMENTS: Primary outcomes were in-hospital mortality and discharge to home. Criteria effects were assessed using chi-square tests, multivariable logistic regression, interrupted time series plots, and multivariable segmented regression models. RESULTS: After geriatric criteria were adopted, the proportion of older adults qualifying for trauma center transport increased from 44% to 58%, but EMS transport rates did not change (44% vs 45%). There was no difference in unadjusted mortality (7.1% vs 6.6%) (P = .10). In adjusted analyses, subjects with an injury severity score (ISS) less than 10 had lower mortality after adoption (3.0% vs 2.5%) (odds ratio (OR) = 0.81, 95% confidence interval (CI) = 0.70-0.95, P = .01). Discharge to home increased after adoption in the adjusted analysis (OR = 1.06, 95% CI = 1.01-1.11, P = .02). There were no time-dependent changes for either outcome. CONCLUSION: Although the proportion of older adults meeting criteria for trauma center transport substantially increased with geriatric triage criteria, there were no increases in trauma center transports. Adoption of statewide geriatric triage guidelines did not decrease mortality in more severely injured older adults but was associated with slightly lower mortality in individuals with mild injuries (ISS <10) and with more individuals discharged to home. Improving outcomes in injured older adults will require further attention to implementation and use of geriatric-specific criteria.

Geriatric-specific triage criteria are more sensitive than standard adult criteria in identifying need for trauma center care in injured older adults.

STUDY OBJECTIVE: We evaluate the sensitivity of Ohio's 2009 emergency medical services (EMS) geriatric trauma triage criteria compared with the previous adult triage criteria in identifying need for trauma center care among older adults. METHODS: We studied a retrospective cohort of injured patients aged 16 years or older in the 2006 to 2011 Ohio Trauma Registry. Patients aged 70 years or older were considered geriatric. We identified whether each patient met the geriatric and the adult triage criteria. The outcome measure was need for trauma center care, defined by surrogate markers: Injury Severity Score greater than 15, operating room in fewer than 48 hours, any ICU stay, and inhospital mortality. We calculated sensitivity and specificity of both triage criteria for both age groups. RESULTS: We included 101,577 patients; 33,379 (33%) were geriatric. Overall, 57% of patients met adult criteria and 68% met geriatric criteria. Using Injury Severity Score, for older adults geriatric criteria were more sensitive for need for trauma center care (93%; 95% confidence interval [CI] 92% to 93%) than adult criteria (61%; 95% CI 60% to 62%). Geriatric criteria decreased specificity in older adults from 61% (95% CI 61% to 62%) to 49% (95% CI 48% to 49%). Geriatric criteria in older adults (93% sensitivity, 49% specificity) performed similarly to the adult criteria in younger adults (sensitivity 87% and specificity 44%). Similar patterns were observed for other outcomes. CONCLUSION: Standard adult EMS triage guidelines provide poor sensitivity in older adults. Ohio's geriatric trauma triage guidelines significantly improve sensitivity in identifying Injury Severity Score and other surrogate markers of the need for trauma center care, with modest decreases in specificity for older adults.

Development of an inducible caspase-9 safety switch for pluripotent stem cell-based therapies.

Induced pluripotent stem cell (iPSC) therapies offer a promising path for patient-specific regenerative medicine. However, tumor formation from residual undifferentiated iPSC or transformation of iPSC or their derivatives is a risk. Inclusion of a suicide gene is one approach to risk mitigation. We introduced a dimerizable-"inducible caspase-9" (iCasp9) suicide gene into mouse iPSC (miPSC) and rhesus iPSC (RhiPSC) via a lentivirus, driving expression from either a cytomegalovirus (CMV), elongation factor-1 α (EF1α) or pluripotency-specific EOS-C(3+) promoter. Exposure of the iPSC to the synthetic chemical dimerizer, AP1903, in vitro induced effective apoptosis in EF1α-iCasp9-expressing (EF1α)-iPSC, with less effective killing of EOS-C(3+)-iPSC and CMV-iPSC, proportional to transgene expression in these cells. AP1903 treatment of EF1α-iCasp9 miPSC in vitro delayed or prevented teratomas. AP1903 administration following subcutaneous or intravenous delivery of EF1α-iPSC resulted in delayed teratoma progression but did not ablate tumors. EF1α-iCasp9 expression was downregulated during in vitro and in vivo differentiation due to DNA methylation at CpG islands within the promoter, and methylation, and thus decreased expression, could be reversed by 5-azacytidine treatment. The level and stability of suicide gene expression will be important for the development of suicide gene strategies in iPSC regenerative medicine.

Bone marrow homing and engraftment of human hematopoietic stem and progenitor cells is mediated by a polarized membrane domain.

Manipulation of hematopoietic stem/progenitor cells (HSPCs) ex vivo is of clinical importance for stem cell expansion and gene therapy applications. However, most cultured HSPCs are actively cycling, and show a homing and engraftment defect compared with the predominantly quiescent noncultured HSPCs. We previously showed that HSPCs make contact with osteoblasts in vitro via a polarized membrane domain enriched in adhesion molecules such as tetraspanins. Here we show that increased cell cycling during ex vivo culture of HSPCs resulted in disruption of this membrane domain, as evidenced by disruption of polarity of the tetraspanin CD82. Chemical disruption or antibody-mediated blocking of CD82 on noncultured HSPCs resulted in decreased stromal cell adhesion, homing, and engraftment in nonobese diabetic/severe combined immunodeficiency IL-2γ(null) (NSG) mice compared with HSPCs with an intact domain. Most leukemic blasts were actively cycling and correspondingly displayed a loss of domain polarity and decreased homing in NSG mice compared with normal HSPCs. We conclude that quiescent cells, unlike actively cycling cells, display a polarized membrane domain enriched in tetraspanins that mediates homing and engraftment, providing a mechanistic explanation for the homing/engraftment defect of cycling cells and a potential new therapeutic target to enhance engraftment.

Human and rhesus macaque hematopoietic stem cells cannot be purified based only on SLAM family markers.

Various combinations of antibodies directed to cell surface markers have been used to isolate human and rhesus macaque hematopoietic stem cells (HSCs). These protocols result in poor enrichment or require multiple complex steps. Recently, a simple phenotype for HSCs based on cell surface markers from the signaling lymphocyte activation molecule (SLAM) family of receptors has been reported in the mouse. We examined the possibility of using the SLAM markers to facilitate the isolation of highly enriched populations of HSCs in humans and rhesus macaques. We isolated SLAM (CD150(+)CD48(-)) and non-SLAM (not CD150(+)CD48(-)) cells from human umbilical cord blood CD34(+) cells as well as from human and rhesus macaque mobilized peripheral blood CD34(+) cells and compared their ability to form colonies in vitro and reconstitute immune-deficient (nonobese diabetic/severe combined immunodeficiency/interleukin-2 γc receptor(null), NSG) mice. We found that the CD34(+) SLAM population contributed equally or less to colony formation in vitro and to long-term reconstitution in NSG mice compared with the CD34(+) non-SLAM population. Thus, SLAM family markers do not permit the same degree of HSC enrichment in humans and rhesus macaques as in mice.