Dennis W. Ashley

Adult-derived stem cells and their potential for use in tissue repair and molecular medicine.

This report reviews three categories of precursor cells present within adults. The first category of precursor cell, the epiblast‐like stem cell, has the potential of forming cells from all three embryonic germ layer lineages, e.g., ectoderm, mesoderm, and endoderm. The second category of precursor cell, the germ layer lineage stem cell, consists of three separate cells. Each of the three cells is committed to form cells limited to a specific embryonic germ layer lineage. Thus the second category consists of germ layer lineage ectodermal stem cells, germ layer lineage mesodermal stem cells, and germ layer lineage endodermal stem cells. The third category of precursor cells, progenitor cells, contains a multitude of cells. These cells are committed to form specific cell and tissue types and are the immediate precursors to the differentiated cells and tissues of the adult. The three categories of precursor cells can be readily isolated from adult tissues. They can be distinguished from each other based on their size, growth in cell culture, expressed genes, cell surface markers, and potential for differentiation. This report also discusses new findings. These findings include the karyotypic analysis of germ layer lineage stem cells; the appearance of dopaminergic neurons after implantation of naive adult pluripotent stem cells into a 6‐hydroxydopamine‐lesioned Parkinsons model; and the use of adult stem cells as transport mechanisms for exogenous genetic material. We conclude by discussing the potential roles of adult‐derived precursor cells as building blocks for tissue repair and as delivery vehicles for molecular medicine.

Regional, ontogenetic, and sex-related variations in elastic properties of cortical bone in baboon mandibles

Understanding the mechanical features of cortical bone and their changes with growth and adaptation to function plays an important role in our ability to interpret the morphology and evolution of craniofacial skeletons. We assessed the elastic properties of cortical bone of juvenile and adult baboon mandibles using ultrasonic techniques. Results showed that, overall, cortical bone from baboon mandibles could be modeled as an orthotropic elastic solid. There were significant differences in the directions of maximum stiffness, thickness, density, and elastic stiffness among different functional areas, indicating regional adaptations. After maturity, the cortical bone becomes thicker, denser, and stiffer, but less anisotropic. There were differences in elastic properties of the corpus and ramus between male and female mandibles which are not observed in human mandibles. There were correlations between cortical thicknesses and densities, between bone elastic properties and microstructural configuration, and between the directions of maximum stiffness and bone anatomical axes in some areas. The relationships between bone extrinsic and intrinsic properties bring us insights into the integration of form and function in craniofacial skeletons and suggest that we need to consider both macroscopic form, microstructural variation, and the material properties of bone matrix when studying the functional properties and adaptive nature of the craniofacial skeleton in primates. The differences between baboon and human mandibles is at variance to the pattern of differences in crania, suggesting differences in bone adaption to varying skeletal geometries and loading regimes at both phylogenetic and ontogenetic levels.

Rib fracture fixation in the 65 years and older population: A paradigm shift in management strategy at a Level I trauma center.

BACKGROUND Rib fractures after chest wall trauma are a common injury; however, they carry a significant morbidity and mortality risk. The impact of rib fractures in the 65-year and older patient population has been well documented as have the mortality and pneumonia rates. We hypothesize that patients 65 years and older receiving rib plating (RP) have decreased mortality, complication rates, and an accelerated return to normal functional states when compared with controls. METHODS With institutional review board approval, a retrospective review analyzed patients 65 years and older with rib fractures admitted from 2009 to 2015 receiving RP (RP group) (n = 23) compared to nonoperative, injury-matched controls admitted from 2003 to 2008 (NO group) (n = 50). Patients were followed prospectively with regard to lifestyle and functional satisfaction. Independent variables analyzed included Injury Severity Score (ISS), number of rib fractures, mortalities, hospital days, intensive care unit days, pneumonia development, respiratory complications, readmission rates, need for and length of rehabilitation stay time. Comparisons were by &khgr;2 tests/Fishers exact tests, Students t tests and Wilcoxon rank sum tests. RESULTS From 2003 to 2008, 50 NO patients were admitted with ages ranging 65 to 97 years, average ISS of 18.47 (14.28–22.66) versus ages ranging from 63 to 89 years, average ISS of 20.71 (15.7–25.73) for the RP group (n = 23). Average hospital days were 16.76 (10.35–23.18) and 18.36 (13.61–23.11) in the NO and RP groups, respectively. Average intensive care unit days were 11.65 (6.45–16.85) and 8.29 (5.31–11.26) days in the NO and RP groups, respectively. Four respiratory readmissions, two deaths, seven pneumonias, seven pleural-effusions, and 19 recurrent pneumothoraces were encountered in the NO group versus 0 in the RP group (p < 0.001). An equal percentage of patients in both groups entered rehabilitation facilities with average stay time of 18.5 and 28.53 days for the RP and NO groups, respectively. CONCLUSION RP in the 65-year and older trauma population demonstrates a measurable decrease in mortality and respiratory complications, improves respiratory mechanics, and permits an accelerated return to functioning state. LEVEL OF EVIDENCE Therapeutic/care management study, level IV.

An analysis of the effectiveness of a state trauma system: Treatment at designated trauma centers is associated with an increased probability of survival

BACKGROUND States struggle to continue support for recruitment, funding and development of designated trauma centers (DTCs). The purpose of this study was to evaluate the probability of survival for injured patients treated at DTCs versus nontrauma centers. METHODS We reviewed 188,348 patients from the state’s hospital discharge database and identified 13,953 severely injured patients admitted to either a DTC or a nontrauma center between 2008 and 2012. DRG International Classification of Diseases—9th Rev. Injury Severity Scores (ICISS), an accepted indicator of injury severity, was assigned to each patient. Severe injury was defined as an ICISS less than 0.85 (indicating ≥15% probability of mortality). Three subgroups of the severely injured patients were defined as most critical, intermediate critical, and least critical. A full information maximum likelihood bivariate probit model was used to determine the differences in the probability of survival for matched cohorts. RESULTS After controlling for injury severity, injury type, patient demographics, the presence of comorbidities, as well as insurance type and status, severely injured patients treated at a DTC have a 10% increased probability of survival. The largest improvement was seen in the intermediate subgroup. CONCLUSION Treatment of severely injured patients at a DTC is associated with an improved probability of survival. This argues for continued resources in support of DTCs within a defined statewide network. LEVEL OF EVIDENCE Epidemiologic study, level III.

Heterogeneity in trauma registry data quality: Implications for regional and national performance improvement in trauma

BACKGROUND Led by the American College of Surgeons Trauma Quality Improvement Program, performance improvement efforts have expanded to regional and national levels. The American College of Surgeons Trauma Quality Improvement Program recommends 5 audit filters to identify records with erroneous data, and the Georgia Committee on Trauma instituted standardized audit filter analysis in all Level I and II trauma centers in the state. STUDY DESIGN Audit filter reports were performed from July 2013 to September 2014. Records were reviewed to determine whether there was erroneous data abstraction. Percent yield was defined as number of errors divided by number of charts captured. RESULTS Twelve centers submitted complete datasets. During 15 months, 21,115 patient records were subjected to analysis. Audit filter captured 2,901 (14%) records and review yielded 549 (2.5%) records with erroneous data. Audit filter 1 had the highest number of records identified and audit filter 3 had the highest percent yield. Individual center error rates ranged from 0.4% to 5.2%. When comparing quarters 1 and 2 with quarters 4 and 5, there were 7 of 12 centers with substantial decreases in error rates. The most common missed complications were pneumonia, urinary tract infection, and acute renal failure. The most common missed comorbidities were hypertension, diabetes, and substance abuse. CONCLUSIONS In Georgia, the prevalence of erroneous data in trauma registries varies among centers, leading to heterogeneity in data quality, and suggests that targeted educational opportunities exist at the institutional level. Standardized audit filter assessment improved data quality in the majority of participating centers.

Evaluation of the Georgia trauma system using the American College of Surgeons Needs Based Assessment of Trauma Systems tool

Background The American College of Surgeons Needs Based Assessment of Trauma Systems (NBATS) tool was developed to help determine the optimal regional distribution of designated trauma centers (DTC). The objectives of our current study were to compare the current distribution of DTCs in Georgia with the recommended allocation as calculated by the NBATS tool and to see if the NBATS tool identified similar areas of need as defined by our previous analysis using the International Classification of Diseases, Ninth Revision, Clinical Modification Injury Severity Score (ICISS). Methods Population counts were acquired from US Census publications. Transportation times were estimated using digitized roadmaps and patient zip codes. The number of severely injured patients was obtained from the Georgia Discharge Data System for 2010 to 2014. Severely injured patients were identified using two measures: ICISS<0.85 and Injury Severity Score >15. Results The Georgia trauma system includes 19 level I, II, or III adult DTCs. The NBATS guidelines recommend 21; however, the distribution differs from what exists in the state. The existing DTCs exactly matched the NBATS recommended number of level I, II, or III DTCs in 2 of 10 trauma service areas (TSAs), exceeded the number recommended in 3 of 10 TSAs, and was below the number recommended in 5 of 10 TSAs. Densely populated, or urban, areas tend to be associated with a higher number of existing centers compared with the NBATS recommendation. Other less densely populated TSAs are characterized by large rural expanses with a single urban core where a DTC is located. The identified areas of need were similar to the ones identified in the previous gap analysis of the state using the ICISS methodology. Discussion The tool appears to underestimate the number of centers needed in extensive and densely populated areas, but recommends additional centers in geographically expansive rural areas. The tool signifies a preliminary step in assessing the need for state-wide inpatient trauma center services. Level of evidence Economic, level IV.