Marc de Moya

Long-term outcome of acellular dermal matrix when used for large traumatic open abdomen

BACKGROUND The purpose of this study is to prospectively examine the use of Human Acellular Dermal Matrix (HADM) in trauma patients with large open abdominal wounds and assess the long-term outcome. Previous studies have not examined the long-term outcomes in trauma patients with abdominal wall reconstructions. METHODS An institutional review board approved prospective case series of consecutive patients admitted to a level I university trauma center, who were unable to have their abdomen closed primarily after trauma laparotomy. These patients had HADM placed to attain closure of the abdomen with skin advancement flaps to cover the HADM when possible. Our primary outcome measure was hernia formation and our secondary outcomes were laxity, fistulae, and infections associated with HADM. RESULTS Ten patients were enrolled during a 1-year period. Mean time to HADM placement was 17.2 days +/- 3.6 days. Mean initial defect size was 425.1 cm2 +/- 75.9 cm2 with the largest 770 cm2. Thirty day follow-up showed no recurrence in 100% patients. Six patients remained for long-term follow-up. Follow-up at 60 days demonstrated significant laxity or recurrent hernia or both in 67% of patients, and this increased to 100% by the end of 1 year follow-up. There were no bowel fistulae in these patients closed with HADM but 20% with infection. CONCLUSIONS HADM is an alternative available to reconstruct the unclosable open abdomen with no fistulae formation, however, it is associated with a high rate of laxity in large abdominal wounds.

Blunt traumatic occult pneumothorax: is observation safe?--results of a prospective, AAST multicenter study.

BACKGROUND An occult pneumothorax (OPTX) is found incidentally in 2% to 10% of all blunt trauma patients. Indications for intervention remain controversial. We sought to determine which factors predicted failed observation in blunt trauma patients. METHODS A prospective, observational, multicenter study was undertaken to identify patients with OPTX. Successfully observed patients and patients who failed observation were compared. Multivariate logistic regression was used to identify predictors of failure of observation. OPTX size was calculated by measuring the largest air collection along a line perpendicular from the chest wall to the lung or mediastinum. RESULTS Sixteen trauma centers identified 588 OPTXs in 569 blunt trauma patients. One hundred twenty-one patients (21%) underwent immediate tube thoracostomy and 448 (79%) were observed. Twenty-seven patients (6%) failed observation and required tube thoracostomy for OPTX progression, respiratory distress, or subsequent hemothorax. Fourteen percent (10 of 73) failed observation during positive pressure ventilation. Hospital and intensive care unit lengths of stay, and ventilator days were longer in the failed observation group. OPTX progression and respiratory distress were significant predictors of failed observation. Most patient deaths were from traumatic brain injury. Fifteen percentage of patients in the failed observation group developed complications. No patient who failed observation developed a tension PTX, or experienced adverse events by delaying tube thoracostomy. CONCLUSION Most blunt trauma patients with OPTX can be carefully monitored without tube thoracostomy; however, OPTX progression and respiratory distress are independently associated with observation failure.

Aggressive Early Crystalloid Resuscitation adversely affects Outcomes in Adult Blunt Trauma Patients: An Analysis of the Glue Grant Database

BACKGROUND: Evidence suggests that aggressive crystalloid resuscitation is associated with significant morbidity in various clinical settings. We wanted to assess whether aggressive early crystalloid resuscitation adversely affects outcomes in adult blunt trauma patients. METHODS: Data were derived from the Glue Grant database. Our primary outcome measure was all‐cause in‐hospital mortality. Secondary outcomes included days on mechanical ventilation; intensive care unit (ICU) and hospital length of stay (LOS); inflammatory (acute lung injury and adult respiratory distress syndrome, or multiple‐organ failure) and resuscitation‐related morbidity (abdominal and extremity compartment syndromes or acute renal failure) and nosocomial infections (ventilator‐associated pneumonia, bloodstream, urinary tract, and surgical site infections). RESULTS: In our sample of 1,754 patients, in‐hospital mortality was not affected, but ventilator days (p < 0.001) as well as ICU (p = 0.009) and hospital (p = 0.002) LOS correlated strongly with the amount of crystalloids infused in the first 24 hours after injury. Amount of crystalloid resuscitation was also associated with the development of adult respiratory distress syndrome (p < 0.001), multiple‐organ failure (p < 0.001), bloodstream (p = 0.001) and surgical site infections (p < 0.001), as well as abdominal (p < 0.001) and extremity compartment syndromes (p = 0.028) in a dose‐dependent fashion, when age, Glasgow Coma Scale (GCS), severity of injury and acute physiologic derangement, comorbidities, as well as colloid and blood product transfusions were controlled for. CONCLUSION: Crystalloid resuscitation is associated with a substantial increase in morbidity, as well as ICU and hospital LOS in adult blunt trauma patients. LEVEL OF EVIDENCE: Therapeutic study, level III.

Diagnosis of necrotizing soft tissue infections by computed tomography.

HYPOTHESIS In contrast to previous beliefs, we hypothesize that computed tomography (CT) scanning is sensitive and specific for the diagnosis of necrotizing soft tissue infections (NSTIs). DESIGN Retrospective and prospective case series. SETTING Academic medical center. PATIENTS Patients who were clinically suspected of having NSTIs from January 1, 2003, through April 30, 2009, and who underwent imaging with a 16- or 64-section helical CT scanner were studied. The CT result was considered positive if inflamed and necrotic tissue with or without gas or fluid collections across tissue planes was found. The disease (NSTI) was considered present if surgical exploration revealed elements of infection and necrosis of the soft tissues and pathological analysis confirmed the findings. The disease was considered absent if surgical exploration and pathological analysis failed to identify any of these findings or the patient was successfully treated without surgical exploration. MAIN OUTCOME MEASURES Sensitivity and specificity of CT for diagnosing NSTI. RESULTS Of 67 patients with study inclusion criteria, 58 underwent surgical exploration, and NSTI was confirmed in 25 (43%). The remaining 42 patients had either nonnecrotizing infections during surgical exploration (n = 33) or were treated nonoperatively with successful resolution of the symptoms (n = 9). The sensitivity of CT to identify NSTI was 100%, specificity was 81%, positive predictive value was 76%, and negative predictive value was 100%. No differences were found in demographics, white blood cell count on admission, symptoms, or site of infection between those with a false- or true-positive CT result. CONCLUSIONS A negative CT result reliably excludes the diagnosis of NSTI. A positive CT result correctly identifies the disease with a high likelihood.

Dynamic mechanical response of brain tissue in indentation in vivo, in situ and in vitro

Characterizing the dynamic mechanical properties of brain tissue is deemed important for developing a comprehensive knowledge of the mechanisms underlying brain injury. The results gathered to date on the tissue properties have been mostly obtained in vitro. Learning how these results might differ quantitatively from those encountered in vivo is a critical step towards the development of biofidelic brain models. The present study provides novel and unique experimental results on, and insights into, brain biorheology in vivo, in situ and in vitro, at large deformations, in the quasi-static and dynamic regimes. The nonlinear dynamic response of the cerebral cortex was measured in indentation on the exposed frontal and parietal lobes of anesthetized porcine subjects. Load-unload cycles were applied to the tissue surface at sinusoidal frequencies of 10, 1, 0.1 and 0.01 Hz. Ramp-relaxation tests were also conducted to assess the tissue viscoelastic behavior at longer times. After euthanasia, the indentation test sequences were repeated in situ on the exposed cortex maintained in its native configuration within the cranium. Mixed gray and white matter samples were subsequently excised from the superior cortex to be subjected to identical indentation test segments in vitro within 6-7 h post mortem. The main response features (e.g. nonlinearities, rate dependencies, hysteresis and conditioning) were measured and contrasted in vivo, in situ and in vitro. The indentation response was found to be significantly stiffer in situ than in vivo. The consistent, quantitative set of mechanical measurements thereby collected provides a preliminary experimental database, which may be used to support the development of constitutive models for the study of mechanically mediated pathways leading to traumatic brain injury.

Independent Predictors of Enteric Fistula and Abdominal Sepsis After Damage Control Laparotomy: Results From the Prospective AAST Open Abdomen Registry

IMPORTANCE Enterocutaneous fistula (ECF), enteroatmospheric fistula (EAF), and intra-abdominal sepsis/abscess (IAS) are major challenges for surgeons caring for patients undergoing damage control laparotomy after trauma. OBJECTIVE To determine independent predictors of ECF, EAF, or IAS in patients undergoing damage control laparotomy after trauma, using the AAST Open Abdomen Registry. DESIGN The AAST Open Abdomen registry of patients with an open abdomen following damage control laparotomy was used to identify patients who developed ECF, EAF, or IAS and to compare these patients with those without these complications. Univariate analyses were performed to compare these groups of patients. Variables from univariate analyses differing at P < .20 were entered into a stepwise logistic regression model to identify independent risk factors for ECF, EAF, or IAS. SETTING Fourteen level I trauma centers. PARTICIPANTS A total of 517 patients with an open abdomen following damage control laparotomy. MAIN OUTCOMES AND MEASURES Complication of ECF, EAF, or IAS. RESULTS More patients in the ECF/EAF/IAS group than in the group without these complications underwent bowel resection (63 of 111 patients [57%] vs 133 of 406 patients [33%]; P < .001). Within the first 48 hours after surgery, the ECF/EAF/IAS group received more colloids (P < .03) and total fluids (P < .03) than did the group without these complications. The ECF/EAF/IAS group underwent almost twice as many abdominal reexplorations as did the group without these complications (mean [SD] number, 4.1 [4.1] vs 2.2 [3.4]; P < .001). After multivariate analysis, the independent predictors of ECF/EAF/IAS were a large bowel resection (adjusted odds ratio [AOR], 3.56 [95% CI, 1.88-6.76]; P < .001), a total fluid intake at 48 hours of between 5 and 10 L (AOR, 2.11 [95% CI, 1.15-3.88]; P = .02) or more than 10 L (AOR, 1.93 [95% CI, 1.04-3.57]; P = .04), and an increasing number of reexplorations (AOR, 1.14 [95% CI, 1.06-1.21]; P < .001). CONCLUSIONS AND RELEVANCE Large bowel resection, large-volume fluid resuscitation, and an increasing number of abdominal reexplorations were statistically significant predictors of ECF, EAF, or IAS in patients with an open abdomen after damage control laparotomy.

Pulmonary Embolism and Deep Venous Thrombosis in Trauma: Are They Related?

HYPOTHESIS Pulmonary embolism (PE) and deep venous thrombosis (DVT) in trauma are related. DESIGN Retrospective review of medical records. SETTING Academic level I trauma center. PATIENTS Trauma patients who underwent computed tomographic pulmonary angiography (CTPA) with computed tomographic venography (CTV) of the pelvic and proximal lower extremity veins over a 3-year period (January 1, 2004, to December 31, 2006) were reviewed. Data on demographics, injury type and severity, imaging findings, hospital length of stay, and mortality were collected. MAIN OUTCOME MEASURES Pulmonary embolism and DVT. RESULTS Among 247 trauma patients undergoing CTPA/CTV, PE was diagnosed in 46 (19%) and DVT in 18 (7%). Eighteen PEs were central (main or lobar pulmonary arteries), and 28 PEs were peripheral (segmental or subsegmental branches). Pulmonary embolism occurred within the first week of injury in two-thirds of patients. Seven patients with PE (4 femoral, 2 popliteal, and 1 iliac) had DVT. Pulmonary embolism was central in 5 patients and peripheral in 2 patients. No significant differences were noted in any of the examined variables between patients with PE having DVT and those not having DVT. CONCLUSIONS Few patients with PE have DVT of the pelvic or proximal lower extremity veins. Pulmonary embolism may not originate from these veins, as commonly believed, but instead may occur de novo in the lungs. These findings have implications for thromboprophylaxis and, particularly, the value of vena cava filters.

Successful Nonoperative Management of the Most Severe Blunt Renal Injuries: A Multicenter Study of the Research Consortium of New England Centers for Trauma

IMPORTANCE Severe renal injuries after blunt trauma cause diagnostic and therapeutic challenges for the treating clinicians. The need for an operative vs a nonoperative approach is debated. OBJECTIVE To determine the rate, causes, predictors, and consequences of failure of nonoperative management (NOM) in grade IV and grade V blunt renal injuries (BRIs). DESIGN Retrospective case series. SETTING Twelve level I and II trauma centers in New England. PARTICIPANTS A total of 206 adult patients with a grade IV or V BRI who were admitted between January 1, 2000, and December 31, 2011. MAIN OUTCOMES AND MEASURES Failure of NOM, defined as the need for a delayed operation or death due to renal-related complications during NOM. RESULTS Of 206 patients, 52 (25.2%) were operated on immediately, and 154 (74.8%) were managed nonoperatively (with the assistance of angiographic embolization for 25 patients). Nonoperative management failed for 12 of the 154 patients (7.8%) and was related to kidney injury in 10 (6.5%). None of these 10 patients had complications because of the delay in BRI management. The mean (SD) time from admission to failure was 17.6 (27.4) hours (median time, 7.5 hours; range, 4.5-102 hours), and the cause was hemodynamic instability in 10 of the 12 patients (83.3%). Multivariate analysis identified 2 independent predictors of NOM failure: older than 55 years of age and a road traffic crash as the mechanism of injury. When both risk factors were present, NOM failure occurred for 27.3% of the patients; when both were absent, there were no NOM failures. Of the 142 patients successfully managed nonoperatively, 46 (32.4%) developed renal-related complications, including hematuria (24 patients), urinoma (15 patients), urinary tract infection (8 patients), renal failure (7 patients), and abscess (2 patients). These patients were managed successfully with no loss of renal units (ie, kidneys). The renal salvage rate was 76.2% for the entire population and 90.3% among patients selected for NOM. CONCLUSIONS AND RELEVANCE Hemodynamically stable patients with a grade IV or V BRI were safely managed nonoperatively. Nonoperative management failed for only 6.5% of patients owing to renal-related injuries, and three-fourths of the entire population retained their kidneys.

Intraparenchymal vs Extracranial Ventricular Drain Intracranial Pressure Monitors in Traumatic Brain Injury: Less Is More?

BACKGROUND Management of severe traumatic brain injury has centered on continuous intracranial pressure (ICP) monitoring with intraparenchymal ICP monitors (IPM) or extracranial ventricular drains (EVD). Our hypothesis was that neurologic outcomes are unaffected by the type of ICP monitoring device. STUDY DESIGN We reviewed 377 adult patients with traumatic brain injury requiring ICP monitoring. Primary outcome was Glasgow Outcome Score (GOS) 1 month after injury. Secondary outcomes included mortality, monitoring-related complications, and length of ICU and hospital stay. RESULTS There were 253 patients managed with an IPM and 124 with an EVD. There was no difference in Glasgow Outcome Score (2.7 ± 1.3 vs 2.5 ± 1.3, p = 0.45), mortality (30.9% vs 32.2%, p = 0.82), and hospital length of stay (LOS) (15.6 ± 12.4 days vs 16.4 ± 10.7 days, p = 0.57). Device-related complications (11.9% vs 31.1%, p < 0.001), duration of ICP monitoring (3.8 ± 2.6 days vs 7.3 ± 5.6 days, p < 0.001), and ICU LOS (7.6 ± 5.6 days vs 9.5 ± 6.2 days, p = 0.004) were longer in the EVD group. Age, opening ICP, and size of midline shift were independent predictors for neurologic outcomes and mortality, when type and severity of brain injury, as well as overall injury severity were controlled for. Duration of ICP monitoring and opening ICP were independent predictors for hospital LOS and the former predicted prolonged ICU stay. Device-related complications were affected by type of device. CONCLUSIONS Use of EVDs in adult traumatic brain injury patients is associated with prolonged ICP monitoring, ICU LOS, and more frequent device-related complications.

Histone deacetylase inhibitors prevent apoptosis following lethal hemorrhagic shock in rodent kidney cells

BACKGROUND We have previously demonstrated that treatment with histone deacetylase inhibitors (HDACI), such as valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA), can improve survival after hemorrhagic shock in animal models. Hemorrhage results in hypoacetylation of proteins which is reversed by HDACI. These agents are known to acetylate insulin receptor substrate-I (IRS-I), which in turn activates the Akt survival pathway. This study investigated whether HDACI exert their beneficial effects through the Akt survival pathway. METHODS Wistar-Kyoto rats (N=21) underwent hemorrhage (60% blood loss) and were randomized into 3 groups; no resuscitation (NR), and treatment with VPA or SAHA. Kidneys were harvested at 1, 6, and 24h after HDACI treatment and analyzed for acetylated histone 3 at lysine 9 residue (Ac-H3K9), phosphorylated Akt (phospho-Akt), BAD and Bcl-2 proteins. RESULTS Hemorrhaged animals were in severe shock, with mean arterial pressures of 25-30mmHg and lactic acid 7-9mg/ml. Only animals treated with VPA and SAHA survived to the 6- and 24-h timepoints. Treatment with HDACI produced a biologic effect on rat kidney cells inducing acetylation of histone H3K9, which peaked after 1h of treatment, and was statistically significant in the VPA group (p=0.01) compared to NR. Phospho-Akt protein increased in the VPA group with a reciprocal decrease in the pro-apoptotic BAD protein in both groups which was statistically significant in the VPA group after 1h (p=0.007) and 24h (p=0.006) of treatment and in the SAHA group after 24h of treatment (p=0.028). Anti-apoptotic Bcl-2 protein markedly increased after 6 (p=0.04) and 24h (p=0.014) of VPA treatment. Bcl-2 also increased in the SAHA group, but failed to reach statistical significance. CONCLUSION Treatment with HDACI increases phosphorylation of Akt with a subsequent decrease in the pro-apoptotic BAD protein. The above mechanism facilitates the action of anti-apoptotic protein Bcl-2. HDACI protect kidney cells subjected to hemorrhagic shock in rodents through the Akt survival pathway.