Findings on Repeat Posttraumatic Brain Computed Tomography Scans in Older Patients With Minimal Head Trauma and the Impact of Existing Antithrombotic Use.

STUDY OBJECTIVE: Evaluate the utility of routine rescanning of older, mild head trauma patients with an initial negative brain computed tomography (CT), who is on a preinjury antithrombotic (AT) agent by assessing the rate of delayed intracranial hemorrhage (dICH), need for surgery, and attributable mortality. METHODS: Participating centers were trained and provided data collection instruments per institutional review board-approved protocols. Data were obtained from manual chart review and electronic medical record download. Adults ≥55 years seen at Level I/II Trauma Centers, between 2017 and 2019 with suspected head trauma, Glasgow Coma Scale 14 to 15, negative initial brain CT, and no other Abbreviated Injury Scale injuries >2 were identified, grouped by preinjury AT therapy (AT- or AT+) and compared on dICH rate, need for operative neurosurgical intervention, and attributable mortality using univariate analysis (α=.05). RESULTS: A total of 2,950 patients from 24 centers were enrolled; 280 (9.5%) had a repeat brain CT. In those rescanned, the dICH rate was 15/126 (11.9%) for AT- and 6/154 (3.9%) in AT+. Assuming nonrescanned patients did not suffer clinically meaningful dICH, the dICH rate would be 15/2001 (0.7%) for AT- and 6/949 (0.6%) for AT+. No surgical operations were done for dICH. All-cause mortality was 9/2950 (0.3%) and attributable mortality was 1/2950 (0.03%). The attributable death was an AT+, dICH patient whose family declined intervention. CONCLUSION: In older patients with an initial Glasgow Coma Scale of 14 to 15 and a negative initial brain CT scan, the dICH rate is low (<1%) and of minimal clinical consequence, regardless of AT use. In addition, no patient had operative neurosurgical intervention. Therefore, routine rescanning is not supported based on the results of this study.

Risk factors for recurrence in blunt traumatic abdominal wall hernias: A secondary analysis of a Western Trauma association multicenter study.

BACKGROUND: Few studies have investigated risk factors for recurrence of blunt traumatic abdominal wall hernias (TAWH). METHODS: Twenty trauma centers identified repaired TAWH from January 2012 to December 2018. Logistic regression was used to investigate risk factors for recurrence. RESULTS: TAWH were repaired in 175 patients with 21 (12.0%) known recurrences. No difference was found in location, defect size, or median time to repair between the recurrence and non-recurrence groups. Mesh use was not protective of recurrence. Female sex, injury severity score (ISS), emergency laparotomy (EL), and bowel resection were associated with hernia recurrence. Bowel resection remained significant in a multivariable model. CONCLUSION: Female sex, ISS, EL, and bowel resection were identified as risk factors for hernia recurrence. Mesh use and time to repair were not associated with recurrence. Surgeons should be mindful of these risk factors but could attempt acute repair in the setting of appropriate physiologic parameters.

Impact of time to surgery on mortality in hypotensive patients with noncompressible torso hemorrhage: An AAST multicenter, prospective study.

BACKGROUND: Death from noncompressible torso hemorrhage (NCTH) may be preventable with improved prehospital care and shorter in-hospital times to hemorrhage control. We hypothesized that shorter times to surgical intervention for hemorrhage control would decrease mortality in hypotensive patients with NCTH. METHODS: This was an AAST-sponsored multicenter, prospective analysis of hypotensive patients aged 15+ years who presented with NCTH from May 2018 to December 2020. Hypotension was defined as an initial systolic blood pressure (SBP) ≤ 90 mm Hg. Primary outcomes of interest were time to surgical intervention and in-hospital mortality. RESULTS: There were 242 hypotensive patients, of which 48 died (19.8%). Nonsurvivors had higher mean age (47.3 vs. 38.8; p = 0.02), higher mean New Injury Severity Score (38 vs. 29; p < 0.001), lower admit systolic blood pressure (68 vs. 79 mm Hg; p < 0.01), higher incidence of vascular injury (41.7% vs. 21.1%; p = 0.02), and shorter median (interquartile range, 25-75) time from injury to operating room start (74 minutes [48-98 minutes] vs. 88 minutes [61-128 minutes]; p = 0.03) than did survivors. Multivariable Cox regression showed shorter time from emergency department arrival to operating room start was not associated with improved survival (p = 0.04). CONCLUSION: Patients who died arrived to a trauma center in a similar time frame as did survivors but presented in greater physiological distress and had significantly shorter times to surgical hemorrhage intervention than did survivors. This suggests that even expediting a critically ill patient through the current trauma system is not sufficient time to save lives from NCTH. Civilian prehospital advance resuscitative care starting from the patient first contact needs special consideration. LEVEL OF EVIDENCE: Prognostic/Epidemiologic, Level III.

The public health burden of geriatric trauma: Analysis of 2,688,008 hospitalizations from Centers for Medicare and Medicaid Services inpatient claims.

BACKGROUND: Geriatric trauma care (GTC) represents an increasing proportion of injury care, but associated public health research on outcomes and expenditures is limited. The purpose of this study was to describe GTC characteristics, location, diagnoses, and expenditures. METHODS: Patients at short-term nonfederal hospitals, 65 years or older, with ≥1 injury International Classification of Diseases, Tenth Revision, were selected from 2016 to 2019 Centers for Medicare and Medicaid Services Inpatient Standard Analytical Files. Trauma center levels were linked to Inpatient Standard Analytical Files data via American Hospital Association Hospital ID and fuzzy string matching. Demographics, care location, diagnoses, and expenditures were compared across groups. RESULTS: A total of 2,688,008 hospitalizations (62% female; 90% White; 71% falls; mean Injury Severity Score, 6.5) from 3,286 hospitals were included, comprising 8.5% of all Medicare inpatient hospitalizations. Level I centers encompassed 7.2% of the institutions (n = 236) but 21.2% of hospitalizations, while nontrauma centers represented 58.5% of institutions (n = 1,923) and 37.7% of hospitalizations. Compared with nontrauma centers, patients at Level I centers had higher Elixhauser scores (9.0 vs. 8.8) and Injury Severity Score (7.4 vs. 6.0; p < 0.0001). The most frequent primary diagnosis at all centers was hip/femur fracture (28.3%), followed by traumatic brain injury (10.1%). Expenditures totaled $32.9 billion for trauma-related hospitalizations, or 9.1% of total Medicare hospitalization expenditures and approximately 1.1% of the annual Medicare budget. The overall mortality rate was 3.5%. CONCLUSION: Geriatric trauma care accounts for 8.5% of all inpatient GTC and a similar percentage of expenditures, the most common injury being hip/femur fractures. The largest proportion of GTC occurs at nontrauma centers, emphasizing their vital role in trauma care. Public health prevention programs and GTC guidelines should be implemented by all hospitals, not just trauma centers. Further research is required to determine the optimal role of trauma systems in GTC, establish data-driven triage guidelines, and define the impact of trauma centers and nontrauma centers on GTC mortality. LEVEL OF EVIDENCE: Therapeutic/care management, Level III.

An analysis of police transport in an Eastern Association for the Surgery of Trauma multicenter trial examining prehospital procedures in penetrating trauma patients.

BACKGROUND: Police transport (PT) of penetrating trauma patients in urban locations has become routine in certain metropolitan areas; however, whether it results in improved outcomes over prehospital Advanced life support (ALS) transport has not been determined in a multicenter study. We hypothesized that PT would not result in improved outcomes. METHODS: This was a multicenter, prospective, observational study of adults (18+ years) with penetrating trauma to the torso and/or proximal extremity presenting at 25 urban trauma centers. Police transport and ALS patients were allocated via nearest neighbor, propensity matching. Transport mode also examined by Cox regression. RESULTS: Of 1,618 total patients, 294 (18.2%) had PT and 1,324 (81.8%) were by ALS. After matching, 588 (294/cohort) remained. The patients were primarily Black (n = 497, 84.5%), males (n = 525, 89.3%, injured by gunshot wound (n = 494, 84.0%) with 34.5% (n = 203) having Injury Severity Score of 16 or higher. Overall mortality by propensity matching was not different between cohorts (15.6% ALS vs. 15.0% PT, p = 0.82). In severely injured patients (Injury Severity Score ≥16), mortality did not differ between PT and ALS transport (38.8% vs. 36.0%, respectively; p = 0.68). Cox regression analysis controlled for relevant factors revealed no association with a mortality benefit in patients transported by ALS. CONCLUSION: Police transport of penetrating trauma patients in urban locations results in similar outcomes compared with ALS. Immediate transport to definitive trauma care should be emphasized in this patient population. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level III.

Dexmedetomidine and paralytic exposure after damage control laparotomy: risk factors for delirium? Results from the EAST SLEEP-TIME multicenter trial.

PURPOSE: To evaluate factors associated with ICU delirium in patients who underwent damage control laparotomy (DCL), with the hypothesis that benzodiazepines and paralytic infusions would be associated with increased delirium risk. We also sought to evaluate the differences in sedation practices between trauma (T) and non-trauma (NT) patients. METHODS: We reviewed retrospective data from 15 centers in the EAST SLEEP-TIME registry admitted from January 1, 2017 to December 31, 2018. We included all adults undergoing DCL, regardless of diagnosis, who had completed daily Richmond Agitation Sedation Score (RASS) and Confusion Assessment Method-ICU (CAM-ICU). We excluded patients younger than 18 years, pregnant women, prisoners and patients who died before the first re-laparotomy. Data collected included age, number of re-laparotomies after DCL, duration of paralytic infusion, duration and type of sedative and opioid infusions as well as daily CAM-ICU and RASS scores to analyze risk factors associated with the proportion of delirium-free/coma-free ICU days during the first 30 days (DF/CF-ICU-30) using multivariate linear regression. RESULTS: A 353 patient subset (73.2% trauma) from the overall 567-patient cohort had complete daily RASS and CAM-ICU data. NT patients were older (58.9 ± 16.0 years vs 40.5 ± 17.0 years [p < 0.001]). Mean DF/CF-ICU-30 days was 73.7 ± 96.4% for the NT and 51.3 ± 38.7% in the T patients (p = 0.030). More T patients were exposed to Midazolam, 41.3% vs 20.3% (p = 0.002). More T patients were exposed to Propofol, 91.0% vs 71.9% (p < 0.001) with longer infusion times in T compared to NT (71.2 ± 85.9 vs 48.9 ± 69.8 h [p = 0.017]). Paralytic infusions were also used more in T compared to NT, 34.8% vs 18.2% (p < 0.001). Using linear regression, dexmedetomidine infusion and paralytic infusions were associated with decreases in DF/CF-ICU-30, (- 2.78 (95%CI [- 5.54, - 0.024], p = 0.040) and (- 7.08 ([- 13.0, - 1.10], p = 0.020) respectively. CONCLUSIONS: Although the relationship between paralytic use and delirium is well-established, the observation that dexmedetomidine exposure is independently associated with increased delirium and coma is novel and bears further study.

Factors associated with stroke formation in blunt cerebrovascular injury: An EAST multicenter study.

BACKGROUND: Stroke risk factors after blunt cerebrovascular injury (BCVI) are ill-defined. We hypothesized that factors associated with stroke for BCVI would include medical therapy (i.e., Aspirin), radiographic features, and protocolization of care. METHODS: An Eastern Association for the Surgery of Trauma-sponsored, 16-center, prospective, observational trial was undertaken. Stroke risk factors were analyzed individually for vertebral artery (VA) and internal carotid artery (ICA) BCVI. Blunt cerebrovascular injuries were graded on the standard 1 to 5 scale. Data were from the initial hospitalization only. RESULTS: Seven hundred seventy-seven BCVIs were included. Stroke rate was 8.9% for all BCVIs, with an 11.7% rate of stroke for ICA BCVI and a 6.7% rate for VA BCVI. Use of a management protocol (p = 0.01), management by the trauma service (p = 0.04), antiplatelet therapy over the hospital stay (p < 0.001), and Aspirin therapy specifically over the hospital stay (p < 0.001) were more common in ICA BCVI without stroke compared with those with stroke. Antiplatelet therapy over the hospital stay (p < 0.001) and Aspirin therapy over the hospital stay (p < 0.001) were more common in VA BCVI without stroke than with stroke. Percentage luminal stenosis was higher in both ICA BCVI (p = 0.002) and VA BCVI (p < 0.001) with stroke. Decrease in percentage luminal stenosis (p < 0.001), resolution of intraluminal thrombus (p = 0.003), and new intraluminal thrombus (p = 0.001) were more common in ICA BCVI with stroke than without, while resolution of intraluminal thrombus (p = 0.03) and new intraluminal thrombus (p = 0.01) were more common in VA BCVI with stroke than without. CONCLUSION: Protocol-driven management by the trauma service, antiplatelet therapy (specifically Aspirin), and lower percentage luminal stenosis were associated with lower stroke rates, while resolution and development of intraluminal thrombus were associated with higher stroke rates. Further research will be needed to incorporate these risk factors into lesion specific BCVI management. LEVEL OF EVIDENCE: Prognostic and Epidemiologic, Level IV.

Management of blunt traumatic abdominal wall hernias: A Western Trauma Association multicenter study.

BACKGROUND: Blunt traumatic abdominal wall hernias (TAWH) occur in approximately 15,000 patients per year. Limited data are available to guide the timing of surgical intervention or the feasibility of nonoperative management. METHODS: A retrospective study of patients presenting with blunt TAWH from January 2012 through December 2018 was conducted. Patient demographic, surgical, and outcomes data were collected from 20 institutions through the Western Trauma Association Multicenter Trials Committee. RESULTS: Two hundred and eighty-one patients with TAWH were identified. One hundred and seventy-six (62.6%) patients underwent operative hernia repair, and 105 (37.4%) patients underwent nonoperative management. Of those undergoing surgical intervention, 157 (89.3%) were repaired during the index hospitalization, and 19 (10.7%) underwent delayed repair. Bowel injury was identified in 95 (33.8%) patients with the majority occurring with rectus and flank hernias (82.1%) as compared with lumbar hernias (15.8%). Overall hernia recurrence rate was 12.0% (n = 21). Nonoperative patients had a higher Injury Severity Score (24.4 vs. 19.4, p = 0.010), head Abbreviated Injury Scale score (1.1 vs. 0.6, p = 0.006), and mortality rate (11.4% vs. 4.0%, p = 0.031). Patients who underwent late repair had lower rates of primary fascial repair (46.4% vs. 77.1%, p = 0.012) and higher rates of mesh use (78.9% vs. 32.5%, p < 0.001). Recurrence rate was not statistically different between the late and early repair groups (15.8% vs. 11.5%, p = 0.869). CONCLUSION: This report is the largest series and first multicenter study to investigate TAWHs. Bowel injury was identified in over 30% of TAWH cases indicating a significant need for immediate laparotomy. In other cases, operative management may be deferred in specific patients with other life-threatening injuries, or in stable patients with concern for bowel injury. Hernia recurrence was not different between the late and early repair groups. LEVEL OF EVIDENCE: Therapeutic/care management, Level IV.

The Impact of Nursing on Trauma Patient Satisfaction: An Analysis of HCAHPS From 112,283 Patients.

BACKGROUND: Assessment of patient satisfaction is central to understanding and improving system performance with the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) national standard survey. However, no large, multi-institutional study exists, which examines the role of nurses in trauma patient satisfaction. OBJECTIVE: To assess the impact of nurses on trauma patient satisfaction. METHODS: This retrospective, descriptive study of Level I-IV trauma centers in a multistate hospital system evaluated patients 18 years and older admitted with at least an overnight stay. Data were obtained electronically for patients discharged in 2018-2019 who returned an HCAHPS survey. Surveys were linked by an honest broker to demographic and injury data from the trauma registry, and then anonymized prior to analysis. Patients were categorized as "trauma" per the National Trauma Data Standard (NTDS) definition or as "medical" or "surgical" per the HCAHPS definition. RESULTS: Of 112,283 surveys from 89 trauma centers, "trauma" patients (n = 5,126) comprised 4.6%, "surgical" 39.0% (n = 43,763), and "medical" 56.5% (n = 63,394). Nurses had an overwhelming impact on "trauma" patient satisfaction, accounting for 63.9% (p < .001) of the variation (adjusted R2) in the overall score awarded the institution-larger than for "surgery" (59.6%; p < .001) or "medical" (58.4%; p < .001) patients. The most important individual domain contributor to the overall rating of a facility was "nursing communication." CONCLUSIONS: The magnitude of the effect of trauma nurses was noteworthy, with their communication ability being the single biggest driver of institutional ratings. These data provide insight for future performance benchmark development and emphasize the critical impact of trauma nurses on the trauma patient experience.

Trauma and nontrauma damage-control laparotomy: The difference is delirium (data from the Eastern Association for the Surgery of Trauma SLEEP-TIME multicenter trial).

BACKGROUND: Damage-control laparotomy (DCL) has been used for traumatic and nontraumatic indications. We studied factors associated with delirium and outcome in this population. METHODS: We reviewed DCL patients at 15 centers for 2 years, including demographics, Charlson Comorbidity Index (CCI), diagnosis, operations, and outcomes. We compared 30-day mortality; renal failure requiring dialysis; number of takebacks; hospital, ventilator, and intensive care unit (ICU) days; and delirium-free and coma-free proportion of the first 30 ICU days (DF/CF-ICU-30) between trauma (T) and nontrauma (NT) patients. We performed linear regression for DF/CF-ICU-30, including age, sex, CCI, achievement of primary fascial closure (PFC), small and large bowel resection, bowel discontinuity, abdominal vascular procedures, and trauma as covariates. We performed one-way analysis of variance for DF/CF-ICU-30 against traumatic brain injury severity as measured by Abbreviated Injury Scale for the head. RESULTS: Among 554 DCL patients (25.8% NT), NT patients were older (58.9 ± 15.8 vs. 39.7 ± 17.0 years, p < 0.001), more female (45.5% vs. 22.1%, p < 0.001), and had higher CCI (4.7 ± 3.3 vs. 1.1 ± 2.2, p < 0.001). The number of takebacks (1.7 ± 2.6 vs. 1.5 ± 1.2), time to first takeback (32.0 hours), duration of bowel discontinuity (47.0 hours), and time to PFC were similar (63.2 hours, achieved in 73.5%). Nontrauma and T patients had similar ventilator, ICU, and hospital days and mortality (31.0% NT, 29.8% T). Nontrauma patients had higher rates of renal failure requiring dialysis (36.6% vs. 14.1%, p < 0.001) and postoperative abdominal sepsis (40.1% vs. 17.1%, p < 0.001). Trauma and NT patients had similar number of hours of sedative (89.9 vs. 65.5 hours, p = 0.064) and opioid infusions (106.9 vs. 96.7 hours, p = 0.514), but T had lower DF/CF-ICU-30 (51.1% vs. 73.7%, p = 0.029), indicating more delirium. Linear regression analysis indicated that T was associated with a 32.1% decrease (95% CI, 14.6%-49.5%; p < 0.001) in DF/CF-ICU-30, while achieving PFC was associated with a 25.1% increase (95% CI, 10.2%-40.1%; p = 0.001) in DF/CFICU-30. Increasing Abbreviated Injury Scale for the head was associated with decreased DF/CF-ICU-30 by analysis of variance (p < 0.001). CONCLUSION: Nontrauma patients had higher incidence of postoperative abdominal sepsis and need for dialysis, while T was independently associated with increased delirium, perhaps because of traumatic brain injury. LEVEL OF EVIDENCE: Therapeutic study, level IV.

An Eastern Association for the Surgery of Trauma multicenter trial examining prehospital procedures in penetrating trauma patients.

BACKGROUND: Prehospital procedures (PHP) by emergency medical services (EMS) are performed regularly in penetrating trauma patients despite previous studies demonstrating no benefit. We sought to examine the influence of PHPs on outcomes in penetrating trauma patients in urban locations where transport to trauma center is not prolonged. We hypothesized that patients without PHPs would have better outcomes than those undergoing PHP. METHODS: This was an Eastern Association for the Surgery of Trauma-sponsored, multicenter, prospective, observational trial of adults (18+ years) with penetrating trauma to the torso and/or proximal extremity presenting at 25 urban trauma centers. The impact of PHPs and transport mechanism on in-hospital mortality were examined. RESULTS: Of 2,284 patients included, 1,386 (60.7%) underwent PHP. The patients were primarily Black (n = 1,527, 66.9%) males (n = 1,986, 87.5%) injured by gunshot wound (n = 1,510, 66.0%) with 34.1% (n = 726) having New Injury Severity Score of ≥16. A total of 1,427 patients (62.5%) were transported by Advanced Life Support EMS, 17.2% (n = 392) by private vehicle, 13.7% (n = 312) by police, and 6.7% (n = 153) by Basic Life Support EMS. Of the PHP patients, 69.1% received PHP on scene, 59.9% received PHP in route, and 29.0% received PHP both on scene and in route. Initial scene vitals differed between groups, but initial emergency department vitals did not. Receipt of ≥1 PHP increased mortality odds (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.01-1.83; p = 0.04). Logistic regression showed increased mortality with each PHP, whether on scene or during transport. Subset analysis of specific PHP revealed that intubation (OR, 10.76; 95% CI, 4.02-28.78; p < 0.001), C-spine immobilization (OR, 5.80; 95% CI, 1.85-18.26; p < 0.01), and pleural decompression (OR, 3.70; 95% CI, 1.33-10.28; p = 0.01) had the highest odds of mortality after adjusting for multiple variables. CONCLUSION: Prehospital procedures in penetrating trauma patients impart no survival advantage and may be harmful in urban settings, even when performed during transport. Therefore, PHP should be forgone in lieu of immediate transport to improve patient outcomes. LEVEL OF EVIDENCE: Prognostic, level III.

Critical Role of Trauma and Emergency Surgery Physicians in Patient Satisfaction: An Analysis of Consumer Assessment of Healthcare Providers and Systems, Hospital Version Data from 186,779 Patients and 168 Hospitals in a National Healthcare System.

BACKGROUND: Trauma and emergency surgery patients are unique with regard to the sudden and unexpected nature of their hospitalization and this can adversely affect patient satisfaction, but, to our knowledge, no large study exists examining this issue. The purpose of this study was to investigate the major factors that affect satisfaction scores in trauma and emergency surgery patients. STUDY DESIGN: Consumer Assessment of Healthcare Providers and Systems, Hospital Version survey data from patients discharged in 2018-2019 from facilities in a national hospital system were obtained. Patients were categorized as trauma, emergency surgery, or direct admit surgery (elective surgery). Individual Consumer Assessment of Healthcare Providers and Systems, Hospital Version question scores were regressed on the score for "overall rating" to determine the primary, secondary, and tertiary satisfaction drivers. RESULTS: There were 186,779 patients from 168 hospitals included. As expected, the primary determinant of patient satisfaction was nursing communication for all groups. However, trauma and emergency surgery patients differed from elective surgery patients in that physician communication was the second most important factor in patient satisfaction, accounting for 12.0% (trauma) and 8.6% (emergency surgery) of the total variability in the overall rating beyond the variability explained by the primary driver. If physician communication received low ratings, it was unlikely that high scores in other metrics could compensate to bring the overall score above the 50th percentile. CONCLUSIONS: Acute care surgeons appear to play a uniquely important role in support of Consumer Assessment of Healthcare Providers and Systems, Hospital Version scores. These data emphasize the importance of physician communication, particularly when a prehospital physician-patient relationship does not exist. Future research should explore specific mechanisms by which physicians effectively communicate with patients.

Clinically relevant redifferentiation of fibroblast-like chondrocytes into functional chondrocytes by the low molecular weight fraction of human serum albumin.

OBJECTIVES: Traumatic joint injury induces chondrocyte dysfunction and progressive breakdown of articular cartilage, leading to post-traumatic osteoarthritis (PTOA). In this condition, dysfunctional fibroblast-like chondrocytes (FLCs) no longer express proteins required for cartilage maintenance, such as SOX9 and collagen-type II (COL2). Interleukin-6 (IL-6) has been demonstrated to downregulate expression of these two critical proteins in chondrocytes, and increased IL-6 levels have been measured in patients with PTOA. The <5kDa fraction of human serum albumin (LMWF5A) has been suggested to modulate this pathway, as decreased levels of IL-6 are secreted by immunostimulated LMWF5A-treated macrophages. Our objective was to determine whether LMWF5A induces an in vitro model of FLCs to redifferentiate into functional chondrocytes. METHODS: SOX9 and COL2 were monitored via western blot, and COL2 was detected with immunofluorescence. Aggrecan and IL-6 were quantified by ELISA. Glycosaminoglycan (GAG) levels were quantified with alcian blue. RESULTS: We found that LMWF5A significantly increases the principal cartilage transcription factor SOX9 and the SOX9 target protein COL2 in monolayer-cultured FLCs. Multiple LMWF5A treatments of 3-D pellet FLC cultures over 2wks resulted in a significant decrease in IL-6 and significant increases in the major players of articular cartilage mechanics, aggrecan and highly-sulfated GAGs. CONCLUSIONS: These data support the hypothesis and clinical outcomes of two phase III clinical trials that LMWF5A-treatment induces chondrogenesis and supports functional cartilage. We propose that LMWF5A could maintain articular cartilage integrity in all joints following traumatic injury.

Overcoming the Warburg Effect: Is it the key to survival in sepsis?

Sepsis is a leading cause of mortality in the U.S. and Europe. Sepsis and septic shock are the results of severe metabolic abnormalities following infection. Aerobic glycolysis (the Warburg Effect) is as much a hallmark of sepsis as it is of cancer. Warburg observed that cancer cells generated energy through glycolysis (generation of ATP through degradation of glucose, usually associated with anaerobic conditions) rather than through oxidative phosphorylation (generation of ATP through the mitochondrial inner membrane via the tricarboxylic acid cycle, usually associated with aerobic conditions). Although the initial pathways of cancer and sepsis may be different, the mechanisms which allow aerobic glycolysis to occur, even in the presence of oxygen, are similar. This review provides some evidence that reversing these steps reverses the Warburg Effect in model systems and some pathological consequences of this effect. Therefore, this implies that these steps might be modifiable in sepsis to reverse the Warburg Effect and possibly lead to better outcomes.