Long-term functional outcomes in polytrauma: a fundamentally new approach is needed in prediction.

PURPOSE: Modern trauma care has reduced mortality but poor long-term outcomes with low follow-up rates are common with limited recommendations for improvements. The aim of this study was to describe the impact of severe injury on the health-related quality of life, specifically characterise the non-responder population and to identify modifiable predictors of poorer outcomes. METHODS: Five-year (2012-2016) prospective cohort study was performed at a level 1 trauma centre. Baseline Short-Form Health Survey (SF36) was collected at admission, and at 6 and 12 months postinjury together with demographics, injury mechanism and severity, psychosocial wellbeing, and return to work capacity. RESULTS: Of the 306 consecutive patients [age 52 ± 17 years, male 72%, ISS 21 (17, 29), mortality 5%], 195 (64%) completed questionnaires at baseline, and at 12 months. Preinjury physical health scores were above the general population (53.1 vs. 50.3, p < 0.001) and mental health component was consistent with the population norms (51.7 vs. 52.9, p = 0.065). One year following injury, both physical health (13.2, 95% CI 14.8, 11.6) and mental health scores (6.0, 95% CI 8.1, 3.8) were significantly below age- and sex-adjusted preinjury baselines. Non-responders had similar ISS but with a lower admission GCS, and were more likely to be younger, and without comorbidities, employment, or university education. CONCLUSION: Contrary to their better than population norm preinjury health status, polytrauma patients remain functionally impaired at least 1 year after injury. The identified high risk for non-responding group needs more focused efforts for follow-up. A fundamentally different approach is required in polytrauma research which identify modifiable predictors of poor long-term outcomes.

The outcomes of the most severe polytrauma patients: a systematic review of the use of high ISS cutoffs for performance measurement.

BACKGROUND: This systematic review aimed to describe the outcomes of the most severely injured polytrauma patients and identify the consistent Injury Severity Score based definition of utilised for their definition. This could provide a global standard for trauma system benchmarking. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was applied to this review. We searched Medline, Embase, Cochrane Reviews, CINAHL, CENTRAL from inception until July 2022. Case reports were excluded. Studies in all languages that reported the outcomes of adult and paediatric patients with an ISS 40 and above were included. Abstracts were screened by two authors and ties adjudicated by the senior author. RESULTS: 7500 abstracts were screened after excluding 13 duplicates. 56 Full texts were reviewed and 37 were excluded. Reported ISS groups varied widely between the years 1986 and 2022. ISS groups reported ranged from 40-75 up to 51-75. Mortality varied between 27 and 100%. The numbers of patients in the highest ISS group ranged between 15 and 1451. CONCLUSIONS: There are very few critically injured patients reported during the last 48 years. The most critically injured polytrauma patients still have at least a 50% risk of death. There is no consistent inclusion and exclusion criteria for this high-risk cohort. The current approach to reporting is not suitable for monitoring the epidemiology and outcomes of the critically injured polytrauma patients. LEVEL OF EVIDENCE: Level 4-systematic review of level 4 studies.

Experimental demonstration of diffusion limitations on resolution and SNR in MR microscopy.

PURPOSE: MR microscopy is in principle capable of producing images at cellular resolution (<10 µm), but various factors limit the quality achieved in practice. A recognized limit on the signal to noise ratio and spatial resolution is the dephasing of transverse magnetization caused by diffusion of spins in strong gradients. Such effects may be reduced by using phase encoding instead of frequency encoding read-out gradients. However, experimental demonstration of the quantitative benefits of phase encoding are lacking, and the exact conditions in which it is preferred are not clearly established. We quantify the conditions where phase encoding outperforms a readout gradient with emphasis on the detrimental effects of diffusion on SNR and resolution. METHODS: A 15.2 T Bruker MRI scanner, with 1 T/m gradients, and micro solenoid RF coils < 1 mm in diameter, were used to quantify diffusion effects on resolution and the signal to noise ratio of frequency and phase encoded acquisitions. Frequency and phase encoding's spatial resolution and SNR per square root time were calculated and measured for images at the diffusion limited resolution. The point spread function was calculated and measured for phase and frequency encoding using additional constant time phase gradients with voxels 3-15 µm in dimension. RESULTS: The effect of diffusion during the readout gradient on SNR was experimentally demonstrated. The achieved resolutions of frequency and phase encoded acquisitions were measured via the point-spread-function and shown to be lower than the nominal resolution. SNR per square root time and actual resolution were calculated for a wide range of maximum gradient amplitudes, diffusion coefficients, and relaxation properties. The results provide a practical guide on how to choose between phase encoding and a conventional readout. Images of excised rat spinal cord at 10 µm × 10 µm in-plane resolution demonstrate phase encoding's benefits in the form of higher measured resolution and higher SNR than the same image acquired with a conventional readout. CONCLUSION: We provide guidelines to determine the extent to which phase encoding outperforms frequency encoding in SNR and resolution given a wide range of voxel sizes, sample, and hardware properties.

Bench to bore ramifications of inter-subject head differences on RF shimming and specific absorption rates at 7T.

PURPOSE: This study shows how inter-subject variation over a dataset of 72 head models results in specific absorption rate (SAR) and B1+ field homogeneity differences using common shim scenarios. METHODS: MR-CT datasets were used to segment 71 head models into 10 tissue compartments. These head models were affixed to the shoulders and neck of the virtual family Duke model and placed within an 8 channel transmit surface-loop array to simulate the electromagnetic fields of a 7T imaging experiment. Radio frequency (RF) shimming using the Gerchberg-Saxton algorithm and Circularly Polarized shim weights over the entire brain and select slices of each model was simulated. Various SAR metrics and B1+ maps were calculated to demonstrate the contribution of head variation to transmit inhomogeneity and SAR variability. RESULTS: With varying head geometries the loading for each transmit loop changes as evidenced by changes in S-parameters. The varying shim conditions and head geometries are shown to affect excitation uniformity, spatial distributions of local SAR, and SAR averaging over different pulse sequences. The Gerchberg-Saxton RF shimming algorithm outperforms circularly polarized shimming for all head models. Peak local SAR within the coil most often occurs nearest the coil on the periphery of the body. Shim conditions vary the spatial distribution of SAR. CONCLUSION: The work gives further support to the need for fast and more subject specific SAR calculations to maintain safety. Local SAR10g is shown to vary spatially given shim conditions, subject geometry and composition, and position within the coil.

Magnetic resonance imaging of mean cell size in human breast tumors.

PURPOSE: Cell size is a fundamental characteristic of all tissues, and changes in cell size in cancer reflect tumor status and response to treatments, such as apoptosis and cell-cycle arrest. Unfortunately, cell size can currently be obtained only by pathological evaluation of tumor tissue samples obtained invasively. Previous imaging approaches are limited to preclinical MRI scanners or require relatively long acquisition times that are impractical for clinical imaging. There is a need to develop cell-size imaging for clinical applications. METHODS: We propose a clinically feasible IMPULSED (imaging microstructural parameters using limited spectrally edited diffusion) approach that can characterize mean cell sizes in solid tumors. We report the use of a combination of pulse sequences, using different gradient waveforms implemented on clinical MRI scanners and analytical equations based on these waveforms to analyze diffusion-weighted MRI signals and derive specific microstructural parameters such as cell size. We also describe comprehensive validations of this approach using computer simulations, cell experiments in vitro, and animal experiments in vivo and demonstrate applications in preoperative breast cancer patients. RESULTS: With fast acquisitions (~7 minutes), IMPULSED can provide high-resolution (1.3 mm in-plane) mapping of mean cell size of human tumors in vivo on clinical 3T MRI scanners. All validations suggest that IMPULSED provides accurate and reliable measurements of mean cell size. CONCLUSION: The proposed IMPULSED method can assess cell-size variations in tumors of breast cancer patients, which may have the potential to assess early response to neoadjuvant therapy.

Influence of the timing of internal fixation of femur fractures during shock resuscitation on remote organ damage.

BACKGROUND: Reamed intramedullary nailing is the gold standard for management of femur fractures. Nailing within 24 h is proven to reduce complications from ongoing bleeding, soft-tissue damage and pain. However, when combined with haemorrhagic shock, femur fracture and intramedullary nailing are associated with immune-mediated damage to remote organs. We studied whether delaying fracture fixation until resuscitation was succeeding would lead to a significant reduction in remote organ damage. METHODS: Twenty male rabbits underwent closed femur fracture, haemorrhagic shock, resuscitation and either immediate nailing (group: ImmFix, n = 9), delayed nailing (group: DelFix, n = 8) or just splinting (group: NoFix, n = 3). Haemorrhagic shock was maintained for 60 min. Resuscitation was with shed blood and Hartmann's solution. Animals were euthanized 8 h after fixation; the lungs and small bowel were scored histologically by two pathologists. RESULTS: Groups did not differ in weight, haemorrhage volume or magnitude of shock. At 8 h, there was no difference in end-organ damage between ImmFix and DelFix groups (11.3 ± 1.6 and 13.2 ± 1.6 versus 8.1 ± 1.3 and 12.9 ± 1.1, P = 0.26 between groups). However, the NoFix group had significantly greater end-organ damage when compared with the fixation at any time groups (17.3 ± 2.7 and 17.0 ± 3.3 versus 9.8 ± 1.1 and 13.1 ± 1, P = 0.01 between groups). CONCLUSION: In this laboratory model, we have demonstrated that timely femur fracture fixation outweighs the potential harmful effects of surgery performed during haemorrhagic shock with simultaneous resuscitation. We have failed to demonstrate a difference between immediate and delayed fixation during resuscitation.

Cell necrosis-independent sustained mitochondrial and nuclear DNA release following trauma surgery.

BACKGROUND: Mitochondrial DNA (mtDNA), a potent proinflammatory damage-associated molecular pattern, is released in large titers following trauma. The effect of trauma surgery on mtDNA concentration is unknown. We hypothesized that mtDNA and nuclear DNA (nDNA) levels would increase proportionately with the magnitude of surgery and both would then decrease rapidly. METHODS: In this prospective pilot, plasma was sampled from 35 trauma patients requiring orthopedic surgical intervention at six perioperative time points. Healthy control subjects (n = 20) were sampled. DNA was extracted, and the mtDNA and nDNA were assessed using quantitative polymerase chain reaction. Markers of cell necrosis were also assayed (creatine kinase, lactate dehydrogenase, and aspartate aminotransferase). RESULTS: The free plasma mtDNA and nDNA levels (ng/mL) were increased in trauma patients compared with healthy controls at all time points (mtDNA: preoperative period, 108 [46-284]; postoperative period, 96 [29-200]; 7 hours postoperatively, 88 [43-178]; 24 hours, 79 [36-172]; 3 days, 136 [65-263]; 5 days, 166 [101-434] [healthy controls, 11 (5-19)]) (nDNA: preoperative period, 52 [25-130]; postoperative period, 100 [35-208]; 7 hours postoperatively, 75 [36-139]; 24 hours postoperatively, 85 [47-133]; 3 days, 79 [48-117]; 5 days, 99 [41-154] [healthy controls, 29 (16-54)]). Elevated DNA levels did not correlate with markers of cellular necrosis. mtDNA was significantly elevated compared with nDNA at preoperative period (p = 0.003), 3 days (p = 0.003), and 5 days (p = 0.0014). Preoperative mtDNA levels were greater with shorter time from injury to surgery (p = 0.0085). Postoperative mtDNA level negatively correlated with intraoperative crystalloid infusion (p = 0.0017). Major pelvic surgery (vs. minor) was associated with greater mtDNA release 5 days postoperatively (p < 0.05). CONCLUSION: This pilot of heterogeneous orthopedic trauma patients showed that the release of mtDNA and nDNA is sustained for 5 days following orthopedic trauma surgery. Postoperative, circulating DNA is not associated with markers of tissue necrosis but is associated with surgical invasiveness and is inversely related to intraoperative fluid administration. Sustained elevation of mtDNA levels could be of inflammatory origin and may contribute to postinjury dysfunctional inflammation. LEVEL OF EVIDENCE: Prospective study, level III.

The impact of specialist trauma service on major trauma mortality.

INTRODUCTION: Trauma services throughout the world have had positive effects on trauma-related mortality. Australian trauma services are generally more consultative in nature rather than the North American model of full trauma admission service. We hypothesized that the introduction of a consultative specialist trauma service in a Level I Australian trauma center would reduce mortality of the severely injured. METHODS: A 10-year retrospective study (January 1, 2002-December 31, 2011) was performed on all trauma patients admitted with an Injury Severity Score (ISS) > 15. Patients were identified from the trauma registry, and data for age, sex, mechanism of injury, ISS, survival to discharge, and length of stay were collected. Mortality was examined for patients with severe injury (ISS > 15) and patients with critical injury (ISS > 24) and compared for the three periods: 2002-2004 (without trauma specialist), 2005-2007 (with trauma specialist), and 2008-2011 (with specialist trauma service). RESULTS: A total of 3,869 severely injured (ISS > 15) trauma patients were identified during the 10-year period. Of these, 2,826 (73%) were male, 1,513 (39%) were critically injured (ISS > 24), and more than 97% (3,754) were the victim of blunt trauma. Overall mortality decreased from 12.4% to 9.3% (relative risk, 0.75) from period one to period three and from 25.4% to 20.3% (relative risk, 0.80) for patients with critical injury. A 0.46% per year decrease (p = 0.018) in mortality was detected (odds ratio, 0.63; p < 0.001). For critically injured (ISS > 24), the trend was (0.61% per year; odds ratio, 0.68; p = 0.039). CONCLUSION: The introduction of a specialist trauma service decreased the mortality of patients with severe injury, the model of care should be considered to implement state- and nationwide in Australia. LEVEL OF EVIDENCE: Epidemiologic study, level III.

Epidemiology of acute transfusions in major orthopaedic trauma.

OBJECTIVES: The orthopaedic trauma-related blood product usage is largely unknown. Aim of this study was to describe the epidemiology of early (<24 hours of arrival) blood component use in major orthopaedic trauma. DESIGN: 12-month prospective observational study. SETTING: John Hunter Hospital, Level 1 Trauma Center, New South Wales, Australia. PATIENTS: 64 consecutive trauma admissions identified, who had an orthopaedic injury and required at least 1 unit of packed red blood cells (PRBC) <24 hours of arrival. INTERVENTION: Epidemiological study. MAIN OUTCOME MEASURES: Demographics, orthopaedic injury type, procedure type, injury severity score, timing, place of first unit of transfusion, and blood component volumes were collected. Activation of the massive transfusion protocol was recorded. Primary outcome measures were intensive care unit admission and mortality. RESULTS: From 965 major trauma admissions, 64 had one or more orthopaedic injuries and were transfused <24 hours. Forty-eight percent (31/64) required massive transfusion protocol activation. Average age was 41 ± 21 years, 73% (47/64) men. Eighty-four percent (54/64) required emergent orthopaedic intervention, 41% (22/54) having multiple procedures. Overall mortality was 13% (8/64). Twenty-five percent (16/64) required ≥10 units of PRBC. Average PRBC use was 7.2 ± 6.6 units and fresh frozen plasma use 4.3 ± 5.2 units. Thirty-nine percent (25/64) had a pelvic ring injury or acetabular fracture. Thirty-seven percent (24/64) had at least one femoral shaft fracture. Twenty patients had a total of 23 tibia fractures. CONCLUSIONS: Orthopaedic trauma patients consume the majority of the blood products <24 hours among blunt trauma patients. This resource-intensive group requires frequent urgent surgical interventions and intensive care unit admission. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Tissue oxygen saturation changes during intramedullary nailing of lower-limb fractures.

BACKGROUND: The systemic complications of acute intramedullary nailing (IMN) in trauma patients are well known. There are no reliable methods available to predict these adverse outcomes. Noninvasive near-infrared spectroscopy (NIRS) allows measurement of oxygen saturation within muscle tissue (StO2) and quantification of the potential metabolic and microcirculatory effects of IMN in real time. The aim of this study was to characterize tissue oxygenation changes occurring during reamed IMN. METHODS: Patients undergoing reamed IMN for fixation of a tibia or femur fracture and patients having an open reduction and internal fixation of the ankle (to control for potential effects of anesthesia) had a noninvasive NIRS probe attached to the thenar eminence of the hand. Tissue oxygenation was monitored continuously throughout the operation and digitally recorded for later analysis. Vascular occlusion tests, an established technique with the NIRS device, were performed before canal opening and after nail insertion (at equivalent times in the control group), to establish the presence and nature of changes in systemic microcirculation occurring during the duration of the operation. RESULTS: Tissue oxygenation data were collected on 23 patients undergoing 26 IMN. (mean [SD] age, 36 [19] years; median Injury Severity Score [ISS], 9; interquartile range, 9-12). The control group consisted of 19 patients (mean [SD] age, 41 [18] years; ISS, 4). Remote muscle tissue desaturated significantly faster after IMN compared with the control operation (mean [SD] difference in IMN desaturation rate, 1.8% per minute [2.6% per minute]; mean [SD] difference in control group desaturation rate, -0.6% per minute [1.5% per minute]; p = 0.014). Near infrared-derived muscle oxygen consumption (NIR VO(2)) was significantly increased during the course of IMN compared with the control (mean [SD] difference in IMN NIR VO(2), 19.9 [32.1]; mean [SD] difference in control NIR VO(2), -4.2 [17.9]; p = 0.041). CONCLUSION: IMN causes significant remote microcirculatory changes. The responsiveness of the microcirculation could be a predictor of secondary organ dysfunction. LEVEL OF EVIDENCE: Epidemiologic study, level III.

Acute transfusion practice during trauma resuscitation: who, when, where and why?

BACKGROUND: Early transfusion (ET=within 24h) has been shown to be required in approximately 5% of trauma patients. Critical care transfusion guidelines control transfusion triggers by evidence based cut-offs. Empirical guidelines influence decision making for ET in trauma. AIM: to describe the patterns, indications and timing of ET at level 1 trauma centre. METHODS: A 12-month prospective study was performed on all trauma admissions requiring ET. Demographics, mechanism, injury severity (ISS) were collected. Timing, location, volume, the clinician initiating first unit of transfusion, reason for transfusion was recorded, with corresponding blood gas results and physiological parameters. Mortality, ICU admission, length of stay, need for emergent surgery were outcomes. RESULTS: From 965 trauma admissions 91 (9%) required ET (76% male, median age: 38 (10-88, IQR: 22-59), blunt mechanism: 87%, ISS: 25 (4-66, IQR: 16-34). 43% (39/91) had massive transfusion protocol (MTP) activation. ET was initiated in ED (52%), OR (38%) or ICU (10%). MTP transfusions were started at a median of 0.5h (0.5-4, IQR: 0.5-1.5), whilst non-MTP transfusions were initiated at a median 3h (0.5-23, IQR: 2-9). The first unit of ET was initiated by trauma surgeon (35%), anaesthetist (30%), ED (19%), ICU (13%) and general surgeon (3%). Transfusions triggers at the first unit of transfusion were 'expected or ongoing bleeding' 29%, dropping haemoglobin 26%, haemorrhagic shock 24%, hypotension 10%, tachycardia 8%. Median systolic blood pressure was 90 (45-125, IQR: 80-100), heart rate was 100 (53-163, IQR: 80-120), haemoglobin was 96 (50-166, IQR: 85-114)g/l and base excess was -4.2(-22.1 to 2.7, IQR: -7.2 to 2.4)mmol/l at the time of transfusion. Emergency surgery was required in 86% (78/91). ICU admission rate was 69% (63/91). Mortality was 14%. Low volume transfusion (1-2 units) was more likely to lead to overtransfusion (Hb>110 g/l). CONCLUSION: The prospective evaluation of acutely transfused trauma patients showed a distinct pattern of transfusion triggers as the patient passes from ED to the OT and arrives to the ICU. The conventional transfusion trigger (haemoglobin level) is not appropriate in ET as early transfusion triggers are based on vital signs, blood gas results, injury patterns and anticipated major bleeding.

Patterns of CT use and surgical intervention in upper limb periarticular fractures at a level-1 trauma centre.

OBJECTIVES: The universal availability of CT scanners has led to lower thresholds for imaging despite significant financial costs and radiation exposure. We hypothesised that this recent trend has increased the use of CT for upper limb periarticular fractures and led to more frequent operative management. METHOD: A 5-year retrospective study (01/07/2005-30/06/2010) was performed on all adult patients with upper extremity periarticular fractures (OTA: 11, 13, 21 and 23) admitted to a level-1 trauma centre. Patients were identified from the institution's prospectively maintained OTA classification database. RESULTS: A total of 1734 upper extremity periarticular fractures were identified in 1651 patients. 65% (1132/1734) were operated on. 32% (557/1734) had CT imaging and 78% (431/557) of these had operative management. CT use for all fractures and ages showed no change (0.56%/year, p = 0.210, r(2) = 0.457). Operative intervention increased at a rate of 2.17%/year (p = 0.004, r(2) = 0.959). Within each fracture type, CT rates showed no change. Operative management of proximal humerus and distal radius fractures became more frequent (6.30%/year, p = 0.002, r(2) = 0.969 and 0.96%/year, p = 0.046, r(2) = 0.784 respectively). Fractures around the elbow showed no change. In patients younger than 55 years, only proximal humerus fractures had more frequent imaging (3.17%/year, p = 0.023, r(2) = 0.866). In patients over 55 the frequency of CT scanning did not increase, but they were more frequently operated on (4.09%/year, p = 0.012, r(2) = 0.907). In older patients the rate of surgical intervention increased in all but the distal humerus region, Proximal humerus (6.19%/year, p = 0.015, r(2) = 0.894), proximal forearm (4.57%/year, p = 0.007, r(2) = 0.931) and distal radius (2.70%/year, p = 0.002, r(2) = 0.871). CONCLUSION: During the examined 5-year period no increases of in CT imaging frequency were observed. The significantly increased number of operations among older patients is unlikely to be driven by imaging frequency.