The risk of thromboembolic events with early intravenous 2- and 4-g bolus dosing of tranexamic acid compared to placebo in patients with severe traumatic bleeding: A secondary analysis of a randomized, double-blind, placebo-controlled, single-center trial.

BACKGROUND: Screening for the risk of thromboembolism (TE) due to tranexamic acid (TXA) in patients with severe traumatic injury has not been performed in randomized clinical trials. Our objective was to determine if TXA dose was independently-associated with thromboembolism. STUDY DESIGN AND METHODS: This is a secondary analysis of a single-center, double-blinded, randomized controlled trial comparing placebo to a 2-g or 4-g intravenous TXA bolus dose in trauma patients with severe injury. We used multivariable discrete-time Cox regression models to identify associations with risk for thromboembolic events within 30 days post-enrollment. Event curves were created using discrete-time Cox regression. RESULTS: There were 50 patients in the placebo group, 49 in the 2-g, and 50 in the 4-g TXA group. In adjusted analyses for thromboembolism, a 2-g dose of TXA had an hazard ratio (HR, 95% confidence interval [CI]) of 3.20 (1.12-9.11) (p = .029), and a 4-g dose of TXA had an HR (95% CI) of 5.33 (1.94-14.63) (p = .001). Event curves demonstrated a higher probability of thromboembolism for both doses of TXA compared to placebo. Other parameters independently associated with thromboembolism include time from injury to TXA administration, body mass index, and total blood products transfused. DISCUSSION: In patients with severe traumatic injury, there was a dose-dependent increase in the risk of at least one thromboembolic event with TXA. TXA should not be withheld, but thromboembolism screening should be considered for patients receiving a dose of at least 2-g TXA intravenously for traumatic hemorrhage.

Does Negative Pressure Wound Therapy Impact the Outcome for Patients With Necrotizing Soft Tissue Infection Infected With Anaerobic Bacteria?

Background: A notable improvement in the treatment of necrotizing soft tissue infections (NSTIs) is the development of negative pressure wound therapy (NPWT). Clinicians are still debating whether NPWT is as successful as conventional wet-to-dry dressings at removing bacteria. Recent research has revealed potential oxygen deprivation effects of NPWT in underlying wound tissues, although clinical trials regarding the effects of reduced oxygen on anaerobic bacterial soft tissue infections remain noticeably lacking. Hypothesis: We hypothesized that NPWT-treated patients with NSTIs who were solely infected by anaerobic bacteria would have worse outcomes than those who were infected with other bacterial species. Patients and Methods: Our study included a retrospective examination of the 2008-2022 period of our Acute and Critical Care Surgery database. Patients who had been identified as having necrotizing fasciitis, Fournier gangrene, or gas gangrene and who had their conditions verified by positive wound cultures acquired during the initial debridement and subsequently received NPWT made up the study cohort. Comorbidities, surgical techniques, and clinical results were all covered by the data. Based on their wound infections, patients were divided into two groups: those with exclusively anaerobic NSTIs and those with different bacterial groups (such as polymicrobial and aerobic). Multiple regression, χ2 analysis, and analysis of variance (ANOVA) were among the analytical methods used. Results: One hundred twelve patients with NSTI who had received NPWT comprised the study cohort. Sixteen of these patients (14.3%) had NSTIs that were exclusively anaerobic, whereas the remaining 96 (85.7%) had NSTIs that were mixed aerobic, facultative, or polymicrobial. Between the two groups, there was no difference in the initial wound size. Patients with anaerobic NSTI who underwent NPWT showed a statistically significant increase in the number of debridements (3 [interquartile range {IQR},1-9] vs. 2 [IQR, 1-4]; p = 0.012) and an increased 100-day re-admission rate (37.5% vs. 12.5%; p = 0.012) when compared with patients with non-anaerobic NSTI. The 100-day re-admission rate increased three-fold in NPWT-treated anaerobic NSTIs, according to a logistic regression analysis (odds ratio [OR], 3.63; 95% confidence interval [CI], 1.06-12.44; p = 0.04). Conclusions: In contrast to patients with other bacterial strains, our data show that patients with NSTI treated with NPWT who only have anaerobic bacterial infections have a larger number of debridements and are much more likely to require re-admission within 100 days. We call for additional prospective studies to be conducted to identify additional risk factors and consider alternate treatment options for individuals with exclusively anaerobic NSTIs in light of these findings.

Negative Pressure Wound Therapy With and Without Instillation in Necrotizing Soft Tissue Infections.

Background: Necrotizing soft tissue infections (NSTIs) are rare but deadly infections that require early and often extensive surgical debridement. After debridement, patients frequently have substantial morbidity because of large, open wounds. Hypothesis: Negative pressure wound therapy with instillation (NPWTi) results in higher wound closure rates compared with traditional negative pressure wound therapy (NPWT) or wet to dry dressings (moist wound care dressing). Patients and Methods: A prospectively maintained Acute and Critical Care Surgery database spanning 2008-2018 was queried for patients with a diagnosis of necrotizing fasciitis, Fournier gangrene, or gas gangrene. Data were collected on patient comorbidities, operative management, and clinical outcomes. Patients were stratified by use of moist wound care dressing, traditional NPWT, or NPWTi. Data were analyzed using analysis of variance (ANOVA), χ2, and logistic regression. Results: During the 10-year study period, patients were treated for NSTI; 173 were managed with moist wound care dressing, 150 with NPWT, and 48 with NPWTi. Patients were similar in terms of demographics, body mass index (BMI), diabetes mellitus, and smoking rates. Overall, complication rates were not substantially different, but mortality was higher in the moist wound care dressing group (16.2% vs. 10.7% NPWT vs. 2.1% NPWTi; p = 0.02). In the moist wound care dressing group, 81.5% of patients had an open wound at discharge compared with 52.7% of the NPWT group and only 14.6% of the NPWTi group (p < 0.001). On multivariable regression, NPWTi was associated with closure rates five times higher than the NPWT group (odds ratio [OR], 5.28; 95% confidence interval [CI], 2.40-11.61; p < 0.001) after controlling for smoking status, intravenous drug use, number of operations, and involvement of the most common region of the body. Conclusions: Negative pressure wound therapy with instillation is associated with higher rates of wound closure without increasing complication rates in patients with NSTI compared with traditional NPWT or moist wound care dressing. Although prospective studies are needed, this indicates the potential to improve patient quality of life through reduced pain and outpatient home health needs.

Trauma patients have reduced ex vivo flow-dependent platelet hemostatic capacity in a microfluidic model of vessel injury.

Trauma is the leading cause of death in individuals up to 45 years of age. Alterations in platelet function are a critical component of trauma-induced coagulopathy (TIC), yet these changes and the potential resulting dysfunction is incompletely understood. The lack of clinical assays available to explore platelet function in this patient population has hindered detailed understanding of the role of platelets in TIC. The objective of this study was to assess trauma patient ex vivo flow-dependent platelet hemostatic capacity in a microfluidic model. We hypothesized that trauma patients would have flow-regime dependent alterations in platelet function. Blood was collected from trauma patients with level I activations (N = 34) within 60 min of hospital arrival, as well as healthy volunteer controls (N = 10). Samples were perfused through a microfluidic model of injury at venous and arterial shear rates, and a subset of experiments were performed after incubation with fluorescent anti-CD41 to quantify platelets. Complete blood counts were performed as well as plasma-based assays to quantify coagulation times, fibrinogen, and von Willebrand factor (VWF). Exploratory correlation analyses were employed to identify relationships with microfluidic hemostatic parameters. Trauma patients had increased microfluidic bleeding times compared to healthy controls. While trauma patient samples were able to deposit a substantial amount of clot in the model injury site, the platelet contribution to microfluidic hemostasis was attenuated. Trauma patients had largely normal hematology and plasma-based coagulation times, yet had elevated D-Dimer and VWF. Venous microfluidic bleeding time negatively correlated with VWF, D-Dimer, and mean platelet volume (MPV), while arterial microfluidic bleeding time positively correlated with oxygenation. Arterial clot growth rate negatively correlated with red cell count, and positively with mean corpuscular volume (MCV). We observed changes in clot composition in trauma patient samples reflected by significantly diminished platelet contribution, which resulted in reduced hemostatic function in a microfluidic model of vessel injury. We observed a reduction in platelet clot contribution under both venous and arterial flow ex vivo in trauma patient samples. While our population was heterogenous and had relatively mild injury severity, microfluidic hemostatic parameters correlated with different patient-specific data depending on the flow setting, indicating potentially differential mechanistic pathways contributing to platelet hemostatic capacity in the context of TIC. These data were generated with the goal of identifying key features of platelet dysfunction in bleeding trauma patients under conditions of flow and to determine if these features correlate with clinically available metrics, thus providing preliminary surrogate markers of physiological platelet dysfunction to be further studied across larger cohorts. Future studies will continue to explore those relationships and further define mechanisms of TIC and their relationship with patient outcomes.

Ludwig's Angina: Higher Incidence and Worse Outcomes Associated With the Onset of the Coronavirus Disease 2019 Pandemic.

Background: Ludwig's angina (LA) is a diffuse cellulitis of the submandibular space and adjacent tissues. During the coronavirus disease 2019 (COVID-19) pandemic, odontogenic treatments were often delayed because of the implementation of safety measures to avoid the spread of the virus. We hypothesized that delayed odontogenic treatments associated with the onset of the COVID-19 pandemic would be associated with an increase in the incidence of LA and worse outcomes related to these infections. Patients and Methods: Patients from June 2018 to June 2022 with computed tomography images suggestive of LA and confirmed by ear, nose, throat (ENT) consult were included. We abstracted demographics, outcomes, clinical management, and microbiology. Patients were stratified into pre-COVID and COVID-onset. Our primary outcome, incidence of LA, was defined as: (new LA cases) ÷ (ED evaluations of oral or dental infections × 1.5 years). Results: In the pre-COVID group, we identified 32 of 1,301 patients with LA for an incidence of 0.02 per year. The COVID-onset group consisted of 41 of 641 patients, with an incidence of 0.04 per year. In the COVID-onset group, progression to necrotizing fasciitis was more likely (0% vs. 15%; p < 0.024), and they returned to the operating room for repeated debridement (3% vs. 22%; p < 0.020). Likewise, hospital length of stay, intensive care unit (ICU) length of stay, and ventilator days were higher (4.3 ± 3.5 vs. 9.5 ± 11.3; 1.1 ± 1.2 vs. 9.5 ± 7.1; 0.3 ± 1 vs. 3.6 ± 7.1; p < 0.001). Conclusions: Although the prognosis for dental infections diagnosed early is generally favorable, we observed a notable increase in the incidence of LA after the onset of the COVID-19 pandemic. Moreover, complications stemming from these infections became more severe in the COVID-onset era. Specifically, the likelihood of necrotizing fasciitis showed a substantial increase, accompanied by an increased risk of respiratory failure and mediastinitis.

Open Mandible and Maxillary Fractures Associated with Higher Risk of Infection in Victims of Assault.

Background: Victims of assault (VOA) often present with fractures of the mandible and maxilla. They represent a complex challenge because of possible compromise of the airway, and infection-related complications because of potential involvement of the oral cavity. We hypothesized that open mandible and maxillary fractures in VOA are associated with a higher rate of infection compared with non-VOA patients with open facial fractures. Patients and Methods: Patients admitted to our level 1 trauma center from 2005 to 2020 with a diagnosis of open mandible and maxillary fractures were included. Demographics, mechanisms of injury, fracture location, cultures, infectious complications, antibiotic treatments, and clinical outcomes were abstracted. Patients were stratified by their mechanism of injury into VOA or non-VOA and were compared using χ2 and Student t-test using SPSS (IBM Corp, Armonk, NY). Results: We identified 316 patients with open mandible and maxillary fractures. There were 198 patients categorized as being VOA, and 118 as non-VOA. Nineteen of 316 patients were diagnosed with infection related to the fracture (3.8% abscesses, 1.9% cellulitis, and 1.9% osteomyelitis). Although the Injury Severity Score (ISS) was higher in non-VOA patients (5.8 ± 2.6 vs. 4.9 ± 1.8; p < 0.013), most of the infections were in the VOA cohort (17/19; 89.5%; p < 0.013). Conclusions: Open fractures of the mandible and maxilla in VOA are associated with a greater risk of infection compared with non-victims of assault. The relation between VOA and poor SDH has been studied recently; clinicians should be aware of this association and implement special considerations and appropriate follow-up visits to decrease the rate of infection in this currently expanding population.

Trauma patients can be safely extubated in the emergency department.

BACKGROUND: Many trauma patients are intubated for conditions that fully resolve during their emergency department (ED) stay. Often, these patients remain intubated until after they leave the ED. OBJECTIVE: The objective of this study was to examine the prognosis of patients extubated in the ED. METHODS: Data from the records of adult trauma patients who were intubated and then extubated in the ED at a single trauma referral center were prospectively collected for a quality initiative. Two trained abstractors retrospectively recorded these data as well as additional information from the trauma registry and patient charts. The primary outcome was the need for unplanned reintubation during hospitalization. Additional outcomes were disposition and complications from the extubation. RESULTS: There were 50 eligible patients identified and included in the study. Reasons for the intubation included combative behavior or decreased mental status before computed axial tomography (CT) scan in 24 patients (48%), sedation before the performance of a painful procedure in 18 patients (36%), and seizures before CT scan in 3 patients (6%). None of the patients (0%; 95% confidence interval 0-6%) required unplanned reintubation. Eight (16%) of the patients were able to be discharged from the ED before admission. CONCLUSIONS: Although our findings must be verified in larger, controlled studies, it may be safe to extubate patients in the ED, if the condition necessitating intubation has fully resolved. This practice may reduce admission rates and limit the need for intensive care unit beds for the patients who are admitted.

Fifteen-minute Frequency of Glucose Measurements and the Use of Threshold Alarms: Impact on Mitigating Dysglycemia in Critically Ill Patients.

BACKGROUND: The use of near-continuous blood glucose (BG) monitoring has the potential to improve glycemic control in critically ill patients. The MANAGE IDE trial evaluated the performance of the OptiScanner (OS) 5000 in a multicenter cohort of 200 critically ill patients. METHODS: An Independent Group reviewed the BG run charts of all 200 patients and voted whether unblinded use of the OS, with alarms set at 90 and 130 to 150 mg/dL to alert the clinical team to impending hypoglycemia and hyperglycemia, respectively, would have eliminated episodes of dysglycemia: hypoglycemia, defined as a single BG <70 mg/dL; hyperglycemia, defined as >4 hours of BG >150 mg/dL; severe hyperglycemia, defined as >4 hours of BG >200 mg/dL and increased glucose variability (GV), defined as coefficient of variation (CV) >20%. RESULTS: At least one episode of dysglycemia occurred in 103 (51.5%) of the patients, including 6 (3.0%) with hypoglycemia, 83 (41.5%) with hyperglycemia, 18 (9.0%) with severe hyperglycemia, and 40 (20.0%) with increased GV. Unblinded use of the OS with appropriate alarms would likely have averted 97.1% of the episodes of dysglycemia: hypoglycemia (100.0%), hyperglycemia (96.4%), severe hyperglycemia (100.0%), and increased GV (97.5%). Point accuracy of the OS was very similar to that of the point of care BG monitoring devices used in the trial. CONCLUSION: Unblinded use of the OS would have eliminated nearly every episode of dysglycemia in this cohort of critically ill patients, thereby markedly improving the quality and safety of glucose control.

Acute Acalculous Cholecystitis-Associated Bacteremia Has Worse Outcome.

Background: Acute acalculous cholecystitis (AAC) is an inflammation of the gallbladder without gallstones in the setting of critical illness. It represents 2%-15% of acute cholecystitis (AC) cases. Bacteremia is associated with increased morbidity and mortality rates in patients in the intensive care unit (ICU). The incidence of bacteremia in acute calculous cholecystitis (ACC) has been described; however, the incidence of bacteremia in AAC has not been reported. We hypothesized that patients with AAC have higher bacteremia rates, leading to worse outcomes than in those with ACC. Methods: A prospectively collected acute care surgery (ACS) institutional database of patients treated from 2008 through 2018 was queried for patients having ACC using International Classification of Diseases (ICD) 9 and 10 codes. Demographics, microbiology findings, and outcomes were extracted. Only patients with positive blood cultures were included in the study. We defined two cohorts: AAC with bacteremia and ACC with bacteremia. The Student t-test was used for continuous variables and the χ2 and Fisher exact tests for categorical variables. Multivariable regression was applied, and statistical significance was set at p < 0.05. Results: Of 323 patients with AC, 57 (17.6%) had AAC and 266 (82.4%) had ACC. Of the 19 patients who had a blood culture, 11 (57.8%) were positive. Patients with positive blood cultures had a mean age of 56.7 ± 15.3 years and a mean Body Mass Index (BMI) of 26.7 ± 4.9. The incidence of bacteremia was significantly higher in AAC (n = 6; 10.5% versus n = 5; 1.9 %; p = 0.005), although the time between admission and diagnosis of bacteremia was similar in the two groups (1.2 ± 1.1 versus 0.2 ± 0.5 days; p = 0.128). The patients with AAC and bacteremia were younger (53.8 ± 19.2 versus 60.2 ± 8 years; p = 0.021) and had a longer ICU length of stay (LOS) (12.6 ± 7.2 versus 1.3 ± 2.1 days; p = 0.030). However, there was no difference in the mortality rate in the groups (n = 2; 33.3% versus 1; 20.0%; p = 1.000). After adjusting for age, gender, BMI, and Charlson Comorbidity Index, bacteremia in AAC patients was found to be an independent variable for longer ICU LOS (odds ratio 8.8; 95% confidence interval 1.7-15.9; p = 0.024). Conclusions: The incidence of bacteremia in patients with AAC is five-fold higher and the ICU stay eight days longer than in patients with ACC.

Acute glucose elevation is highly predictive of infection and outcome in critically injured trauma patients.

OBJECTIVE(S): To evaluate whether acute glucose elevation (AGE) is predictive of infection and outcome in critically injured trauma patients during the first 14 days of ICU admission. METHODS: A prospective study was conducted on 2200 patients admitted to the ICU over a 2 1/2 year period. The diagnosis of infection was made via a multidisciplinary fashion utilizing CDC criteria. After early glucose stabilization occurred (no significant change for 48 hours after admission) monitoring for AGE was performed utilizing a computational and graded algorithmic model. Iatrogenic causes of AGE were excluded. Stepwise regression models were performed controlling for age, gender, mechanism of injury, diabetes, injury severity, and APACHE 2 score. ROC curves were used to evaluate the positive predictive value of the test. RESULTS: Seventy-seven percent of the patients in the cohort were males, and were admitted for blunt injuries (n = 1870 or 85%). The mean age, Injury Severity Score, and APACHE score were 44 ± 20 years, 29 ± 13, and 13 ± 7, respectively. The mean admission serum glucose value was 141 ± 36 mg/dL (range, 64-418 mg/dL). A total of 616 (28%) patients were diagnosed with an infection during the first 14 days of admission. AGE had a 91% positive predictive value for infection diagnosis. In addition, AGE was associated with a significant increase in ventilator, ICU, and hospital days as well as mortality even when adjusted for age, injury severity, APACHE score, and diabetes (P < 0.001). CONCLUSIONS: AGE is a highly accurate predictor of infection and should stimulate clinicians to identify a new source of infection.

Inadequate Antibiotic Therapy Results in Higher Recurrence Rate after Drainage of Complicated Peri-Rectal Abscess.

Background: Recommended treatment for complicated peri-rectal abscess is incision and drainage (I&D) in conjunction with antibiotics. However, there is no standard antibiotic regimen for post-operative therapy described in the published literature. Our hypothesis was that appropriate post-operative antibiotic therapy after emergency I&D of complicated peri-rectal abscess will improve patient outcomes. Methods: Data from 58 patients with complicated peri-rectal abscess who underwent emergency I&D were analyzed retrospectively. Demographic, microbiologic, and antibiotic data were abstracted. Adequateness of antibiotics was judged by susceptibility data when available or by comparing the antibiotic spectrum with the type of organisms grown in culture when susceptibility data were not available. The Student t-test and χ2 test were used to analyze continuous and categorical variables, respectively. Multivariable analysis was used to adjust for confounding variables influencing recurrence rates. Results: Of the 58 patients reviewed, 12 were excluded because there was no culture information available or the culture showed no growth. Of the remaining 46 patients, 33 (72%) were male and 29 (63%) were African American. The mean age was 39.4 ± 16.4 years and the Body Mass Index was 28.4 ± 6.6 kg/m2. Culture data revealed mixed aerobic/anaerobic organisms in 17 (37%), mixed aerobic organisms in 15 (32.6%), gram-positive organisms in 9 (19.6%), gram-negative organisms in 2 (4.4%), and other organisms in 3 (6.6%). Twenty-five patients (54.4%) received adequate antibiotic coverage with the remainder inadequately covered. The inadequate antibiotic therapy cohort had a higher re-admission rate for abscess recurrence (n = 6 [28.6%] versus n = 1 [4%]; p = 0.021). More than half were readmitted 30 days or more after the index procedure. There were no differences in length of stay (LOS), intensive care unit LOS, or Charlson Comorbidity Index between the groups. Conclusion: Inadequate antibiotic coverage after I&D of complicated peri-rectal abscess resulted in a six-fold increase in the re-admission rate. A standard oral protocol combining antibiotics covering typical gram-positive, gram-negative, and anaerobic organisms should provide adequate coverage after surgical drainage. Additional prospective studies are needed to elucidate the optimal antibiotic regimen for these patients.

Temporary Abdominal Closure Is Associated with Increased Risk for Fungal Intra-Abdominal Infections in Trauma Patients.

Background: Fungal infections are associated with increased morbidity and death. Few studies have examined risk factors associated with post-operative fungal intra-abdominal infections (FIAIs) in trauma patients after exploratory laparotomy. In this study, we evaluated potential risk factors for acquiring post-operative FIAIs and their impact on clinical outcomes. Methods: This was a retrospective analysis of trauma patients admitted from 2005 to 2018 who underwent exploratory laparotomy and subsequently had development of intra-abdominal infection (IAI). Demographics, comorbidities, culture data, antimicrobial usage, Injury Severity Scores (ISS), and clinical outcomes were abstracted. All post-operative IAIs were evaluated and stratified as either bacterial, fungal, combined, and with or without colonization. All groups were compared. Risk factors for the development of post-operative IAI and clinical outcomes were analyzed by Student t test and chi-square test. Multi-variable logistic regression was used to determine independent predictors of post-operative FIAIs. Results: There were 1675 patients identified as having undergone exploratory laparotomy in the setting of traumatic injury, 161 of whom were suspected of having IAI. A total of 105 (6.2%) patients had a diagnosis of IAI. Of these patients, 40 (38%) received a diagnosis of FIAI. The most common fungal pathogens were unspeciated yeast (48.3%), followed by Candida albicans (42.7%), C. glabrata (4.5%), C. dubliniensis (2.25%), and C. tropicalis (2.25%). There were no significant differences in demographics, comorbidities, and percentage of gastric perforations between FIAI and bacterial IAI (BIAI) groups. Patients with FIAIs, however, had a 75% temporary abdominal closure (TAC) rate compared with 51% in BIAIs (p = 0.01). The FIAI group had higher ISS (27 vs. 22, p = 0.03), longer hospital days (34 vs. 25, p = 0.02), and longer intensive care unit (ICU) days (17 vs. 9, p = 0.006) when compared with BIAI. The FIAI group also had a five-fold greater mortality rate. Logistic regression identified TAC as an independent risk factor for the development of post-operative FIAIs (odds ratio [OR] 6.16, confidence interval [CI] 1.14-28.0, p = 0.02). Conclusions: An FIAI after exploratory laparotomy was associated with greater morbidity and death. A TAC was associated independently with increased risk of FIAI after exploratory laparotomy in the setting of traumatic injury. Clinicians should suspect fungal infections in trauma patients in whom post-operative IAI develops after undergoing exploratory laparotomy using TAC techniques.

The Immunologic Effect of Early Intravenous Two and Four Gram Bolus Dosing of Tranexamic Acid Compared to Placebo in Patients With Severe Traumatic Bleeding (TAMPITI): A Randomized, Double-Blind, Placebo-Controlled, Single-Center Trial.

Background: The hemostatic properties of tranexamic acid (TXA) are well described, but the immunological effects of TXA administration after traumatic injury have not been thoroughly examined. We hypothesized TXA would reduce monocyte activation in bleeding trauma patients with severe injury. Methods: This was a single center, double-blinded, randomized controlled trial (RCT) comparing placebo to a 2 g or 4 g intravenous TXA bolus dose in trauma patients with severe injury. Fifty patients were randomized into each study group. The primary outcome was a reduction in monocyte activation as measured by human leukocyte antigen-DR isotype (HLA-DR) expression on monocytes 72 h after TXA administration. Secondary outcomes included kinetic assessment of immune and hemostatic phenotypes within the 72 h window post-TXA administration. Results: The trial occurred between March 2016 and September 2017, when data collection ended. 149 patients were analyzed (placebo, n = 50; 2 g TXA, n = 49; 4 g TXA, n = 50). The fold change in HLA-DR expression on monocytes [reported as median (Q1-Q3)] from pre-TXA to 72 h post-TXA was similar between placebo [0.61 (0.51-0.82)], 2 g TXA [0.57 (0.47-0.75)], and 4 g TXA [0.57 (0.44-0.89)] study groups (p = 0.82). Neutrophil CD62L expression was reduced in the 4 g TXA group [fold change: 0.73 (0.63-0.97)] compared to the placebo group [0.97 (0.78-1.10)] at 24 h post-TXA (p = 0.034). The fold decrease in plasma IL-6 was significantly less in the 4 g TXA group [1.36 (0.87-2.42)] compared to the placebo group [0.46 (0.19-1.69)] at 72 h post-TXA (p = 0.028). There were no differences in frequencies of myeloid or lymphoid populations or in classical complement activation at any of the study time points. Conclusion: In trauma patients with severe injury, 4 g intravenous bolus dosing of TXA has minimal immunomodulatory effects with respect to leukocyte phenotypes and circulating cytokine levels. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02535949.

Evaluating the Impact of Technique and Mesh Type in Complicated Ventral Hernia Repair: A Prospective Randomized Multicenter Controlled Trial.

BACKGROUND: To our knowledge, there is an absence of prospective randomized multicenter controlled trials evaluating both the impact of technique and mesh type on outcomes in complicated ventral hernia repair. STUDY DESIGN: A prospective randomized multicenter controlled trial of 120 patients at 3 sites was conducted in which patients were randomized to either overlay (anterior component separation) or underlay mesh placement (posterior component separation) and mesh type (human acellular dermis [HADM] vs porcine acellular dermis [PADM]). Key inclusion criteria included hernia size (>200 cm2), BMI < 40 kg/m2, hemoglobin A1C < 7%, tobacco free > 6 weeks and primary fascial closure. Primary outcome was hernia recurrence at 1 year, determined by independent examiner/imaging. Secondary outcomes included complications and patient satisfaction (short form [SF]-36v2). Standardized investigator training included a porcine model followed by a proctored first case by the lead investigator. RESULTS: There were no significant differences in demographics between the 4 groups (age 60 ±12 years, BMI 32 ± 5 kg/m2, 51% female). The overall 1-year recurrence rate was 10.8%. There was no significant difference in recurrence rate by location of mesh placement (overlay 9.8%, underlay 11.9%) or mesh type (HADM 10.3%, PADM 11.3%). Overlay patients had a significantly lower surgical site infection rate (1.6% vs 11.9% p = 0.03), reported better physical functioning (p = 0.001) and role limitation scores (p = 0.04) in the early postoperative period, and achieved the highest physical functioning score during the 12-month period (p < 0.03). CONCLUSIONS: Recurrence rates were not affected by either anatomic location or type of mesh used. To our knowledge, this represents the first prospective randomized multicenter controlled trial that demonstrates similar clinical outcomes using HADM vs PADM (not inferiority, contrary to previously published literature), with several advantages identified using the overlay technique.

Are Patients with Perforated Peptic Ulcers Who are Negative for Helicobacter pylori at a Greater Risk?

Background: The link between Helicobacter pylori infection and peptic ulceration is well established. Recent studies have reported a decrease of H. pylori-related peptic ulcer disease; Helicobacter pylori eradication is likely the cause of this decrease. We hypothesized that patients with H. pylori-positive perforated peptic ulcer disease (PPUD) requiring surgical intervention had worse outcomes than patients with H. pylori-negative PPUD. Patients and Methods: A prospectively collected Acute and Critical Care Surgery registry spanning the years 2008 to 2015 was searched for patients with PPUD and tested for H. pylori serum immunoglobulin G (IgG) test. Patients were divided into two cohorts: H. pylori positive (HPP) and H. pylori negative (HPN). Demographics, laboratory values, medication history, social history, and esophagogastroduodenoscopy were collected. Student t-test was used for continuous variables and χ2 test was used for categorical variables. Linear regression was applied as appropriate. Results: We identified 107 patients diagnosed with PPUD, of whom 79 (74%) patients had H. pylori serum IgG testing. Forty-two (53.2%) tested positive and 37 (46.8%) tested negative. Helicobacter pylori-negative PPUD was more frequent in females (70.27%, p = 0.004), whites (83.78%, p = 0.001) and patients with higher body mass index (BMI) 28.81 ± 8.8 (p = 0.033). The HPN group had a lower serum albumin level (2.97 ± 0.96 vs. 3.86 ± 0.91 p = 0.0001), higher American Society of Anesthesiologists (ASA; 3.11 ± 0.85 vs. 2.60 ± 0.73; p = 0.005), and Charlson comorbidity index (4.81 ± 2.74 vs. 2.98 ± 2.71; p = 0.004). On unadjusted analysis the HPN cohort had a longer hospital length of stay (LOS; 20.20 ± 13.82 vs. 8.48 ± 7.24; p = 0.0001), intensive care unit (ICU) LOS (10.97 ± 11.60 vs. 1.95 ± 4.59; p = 0.0001), increased ventilator days (4.54 ± 6.74 vs. 0.98 ± 2.85; p = 0.004), and higher rates of 30-day re-admission (11; 29.73% vs. 5; 11.91%; p = 0.049). Regression models showed that HPN PPUD patients had longer hospital and ICU LOS by 11 days (p = 0.002) and 8 days (p = 0.002), respectively, compared with HPP PPUD. Conclusion: In contrast to our hypothesis, HPN patients had clinically worse outcomes than HPP patients. These findings may represent a difference in the baseline pathophysiology of the peptic ulcer disease process. Further investigation is warranted.

Early Emergency General Surgery Is Associated with a Higher Incidence of Clostridium difficile Infection.

BACKGROUND: Clostridium difficile infection (CDI) is an important surgical complication. Emergency general surgery (EGS) is a developing area of the acute care surgical practice. Few studies evaluating the incidence and risk factors of CDI in this patient population are available. PATIENTS AND METHODS: A prospectively maintained Acute and Critical Care Surgery registry spanning from 2008 to 2015 was queried for cases of operative EGS with clinical suspicion of CDI post-operatively. Diagnosis of CDI was made using toxin A/B assay in stools. Demographics, co-morbidities, surgical procedures, length of stay (LOS), intensive care unit LOS, antibiotic use, and death were obtained. The patients positive and negative for CDI were compared using chi-squared and Student's t-test. Multi-variable logistic regression was used to determine risk factors for CDI. RESULTS: A total of 550 patients were identified. The total incidence of CDI was 12.7%. There was no significant difference in demographics between CDI positive and negative patients. Average time to CDI diagnosis was 10.1 ± 8.5 days post-operatively. Patients who received three or more antibiotic classes were at higher risk of CDI developing post-operatively (83% vs. 75%, p = 0.04). The CDI positive patients underwent an EGS significantly earlier than CDI negative patients (0.9 ± 2.3 vs. 3.2 ± 9.2 days, p < 0.001). The most common procedures were partial colectomies (21.4%); small bowel resections/repairs (12.9%); gastric repair for perforated peptic ulcer (10%); skin and soft tissue procedure (7.1%), and laparotomies (5.7%). There was no difference in outcomes between the groups. On linear regression, an EGS performed later after admission was an independent risk factor for lower CDI (OR 0.87; CI 95% [0.79-0.96], p < 0.01). CONCLUSION: Patients undergoing an early EGS have a high incidence of CDI. The number of antibiotic classes administered post-operatively affects CDI status. Bowel resections appear to be at increased risk for CDI. Clinicians should have a high index of suspicion and low threshold for testing C. difficile in high-risk EGS patients.

Early aggressive use of fresh frozen plasma does not improve outcome in critically injured trauma patients.

OBJECTIVES: Recent data from Iraq supporting early aggressive use of fresh frozen plasma (FFP) in a 1:1 ratio to packed red blood cells (PRBCs) has led many civilian trauma centers to adopt this resource intensive strategy. METHODS: Prospective data were collected on 806 consecutive trauma patients admitted to the intensive care unit over 2 years. Patients were stratified by PRBC:FFP transfusion ratio over the first 24 hours. Stepwise regression models were performed controlling for age, gender, mechanism of injury, injury severity, and acute physiology and chronic health evaluation (APACHE) 2 score to determine if early aggressive use of PRBC:FFP improved outcome. RESULTS: Seventy-seven percent of patients were male (N = 617) and 85% sustained blunt injury (n = 680). Mean age, injury severity score (ISS), and APACHE score were 43 +/- 20 years, 29 +/- 13, and 13 +/- 7, respectively. Mean number of PRBCs and FFP transfused were 7.7 +/- 12 U, 6 U, and 5 +/- 12 U, respectively. Three hundred sixty-five (45%) patients were transfused in the first 24 hours. Sixty-eight percent (n = 250) of them received both PRBCs and FFP. Analyzing these patients by stepwise regression controlling for all significant variables, the PRBC:FFP ratio did not predict intensive care unit days, hospital days, or mortality even in patients who received massive transfusion (> or = 10 U). Furthermore, there was no significant difference in outcome when comparing patients who had a 1:1 PRBC:FFP ratio with those who did not receive any FFP. CONCLUSION: Early and aggressive use of FFP does not improve outcome after civilian injury. This may reflect inherent differences compared with military injury; however, this practice should be reevaluated.

Blood product transfusion and ventilator-associated pneumonia in trauma patients.

BACKGROUND: Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in trauma patients, with a high mortality rate. Blood transfusion has been identified as an independent risk factor for VAP in critically ill patients. Prior studies in trauma are limited by retrospective design, lack of multivariable analyses, and scant data on the timing of transfusion. We examined critically the relation between blood product transfusion and VAP in trauma patients. METHODS: Prospective observational cohort study of 766 trauma patients admitted to the intensive care unit (ICU), who received mechanical ventilation (MV) for >or= 48 h, and who did not have pneumonia on admission. Late-onset VAP was defined as that occurring >or= 72 h after MV. Only transfusions of red blood cell (RBC) concentrate, fresh-frozen plasma (FFP), or platelets before the onset of VAP were considered. Logistic regression analyses controlled for all variables related significantly to VAP by univariate analysis (sex, Injury Severity Score, and ventilator days and ICU length of stay prior to VAP). RESULTS: A significantly greater proportion of male patients developed VAP. Patients with VAP had a longer duration of MV: The mean number ventilator days prior to VAP was 11.1 +/- 8.0. Transfusion of blood products was an independent risk factor for VAP, and the risk increased with more units transfused. All blood products were associated with a higher risk of VAP (RBC: odds ratio [OR] 4.41; 95% confidence interval [CI] 1.00, 19.54; p = 0.05; FFP: OR 3.34; 95% CI 1.18, 9.43; p = 0.023; platelets: OR 4.19; 95% CI 1.37, 12.83; p = 0.012). CONCLUSION: Blood product transfusion is an independent risk factor for VAP in trauma, and the odds ratio is significantly higher (3.34-4.41) than in published studies of other types of ICU patients (1.89). To reduce the incidence of VAP, all efforts to reduce the transfusion of blood products to trauma patients should be implemented.

Clostridium difficile infection in critically injured trauma patients.

BACKGROUND: Clostridium difficile infection (CDI) is an increasing problem worldwide. To our knowledge, there are no studies evaluating specifically the incidence of CDI in the critically injured trauma population. METHODS: Five hundred eighty-one consecutive critically injured trauma patients were followed prospectively for development of CDI, diagnosed by toxin assay. Testing was ordered on the basis of symptoms. Antibiotic usage was classified as surgical prophylaxis or therapeutic. RESULTS: Nineteen cases of CDI were diagnosed in 581 patients (3.3%). Age, sex, race, and injury severity score (ISS) were similar in patients with and without CDI (p > 0.2); the mean ISS in patients with CDI was 29 points. Intensive care unit length of stay (ICU LOS), ventilator days, and hospital length of stay (HLOS) were significantly higher in the CDI patients. The diagnosis was made a mean of 17 days after admission; however, in four patients (21%), the infections were diagnosed within six days of admission. Fourteen patients (74%) had received therapeutic antibiotics for confirmed or suspected infection prior to the appearance of colitis; four patients (21%) received only intraoperative prophylaxis, and one patient had no antibiotic exposure. These five patients were significantly younger than those who developed CDI after therapeutic antibiotic usage and had significantly shorter HLOS and ICU LOS (p < 0.05). This result persisted after controlling for age using multiple linear regression analysis. CONCLUSIONS: Clostridium difficile infection occurred in 3.3% of patients and was diagnosed as early as the fourth hospital day. We have identified a unique subgroup of younger patients who developed CDI after minimal or no antibiotic exposure. Further study is needed to characterize this population.

Blast injury in a civilian trauma setting is associated with a delay in diagnosis of traumatic brain injury.

High-pressure waves (blast) account for the majority of combat injuries and are becoming increasingly common in terrorist attacks. To our knowledge, there are no data evaluating the epidemiology of blast injury in a domestic nonterrorist setting. Data were analyzed retrospectively on patients admitted with any type of blast injury over a 10-year period at a busy urban trauma center. Injuries were classified by etiology of explosion and anatomical location. Eighty-nine cases of blast injury were identified in 57,392 patients (0.2%) treated over the study period. The majority of patients were male (78%) with a mean age of 40 +/- 17 years. The mean Injury Severity Score was 13 +/- 11 with an admission Trauma and Injury Severity Score of 0.9 +/- 0.2 and Revised Trauma Score of 7.5 +/- 0.8. The mean intensive care unit and hospital length of stay was 2 +/- 7 days and 4.6 +/- 10 days, respectively, with an overall mortality rate of 4.5 per cent. Private dwelling explosion [n = 31 (35%)] was the most common etiology followed by industrial pressure blast [n = 20 (22%)], industrial gas explosion [n = 16 (18%)], military training-related explosion [n = 15 (17%)], home explosive device [n = 8 (9%)], and fireworks explosion [n = 1 (1%)]. Maxillofacial injuries were the most common injury (n = 78) followed by upper extremity orthopedic (n = 29), head injury (n = 32), abdominal (n = 30), lower extremity orthopedic (n = 29), and thoracic (n = 19). The majority of patients with head injury [28 of 32 (88%)] presented with a Glasgow Coma Scale score of 15. CT scans on admission were initially positive for brain injury in 14 of 28 patients (50%). Seven patients (25%) who did not have a CT scan on admission had a CT performed later in their hospital course as a result of mental status change and were positive for traumatic brain injury (TBI). Three patients (11%) had a negative admission CT with a subsequently positive CT for TBI over the next 48 hours. The remaining four patients (14%) were diagnosed with skull fractures. All patients (n = 4) with an admission Glasgow Coma Scale score of less than 8 died from diffuse axonal injury. Blast injury is a complicated disease process, which may evolve over time, particularly with TBI. The missed injury rate for TBI in patients with a Glasgow Coma Scale score of 15 was 36 per cent. More studies are needed in the area of blast injury to better understand this disease process.