Biomarkers for Predicting Burn-Sepsis in Younger Adults and Older Adults: A Single-Centre Cohort Study

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Authors:
Diana Tedesco, Fadi Khalaf, Gregory Pond, Marc Jeschke, Maria Fernanda Hutter, Zachary Ricciuti

Body of Abstract:
Background: Sepsis is a leading cause of mortality in burn patients, posing significant challenges due to its complex presentation and diagnosis. Early and accurate diagnosis of sepsis is critical to improving outcomes, yet current diagnostic methods are limited. Although many studies have linked various biomarker alterations to burn sepsis, few have comprehensively established sepsis as a prognostic factor for these alterations, owing to its time-sensitive progression, population heterogeneity, and the confounding effects of burn injuries. This study addresses this critical gap by examining the longitudinal impact of sepsis on biomarker levels over time in a large cohort of septic and non-septic burn patients, while accounting for key confounding variables, providing valuable insights to improve clinical decision-making and patient care.

Methods: Patients admitted to a regional burn center were assessed for eligibility. Inclusion criteria included adults (≥18 years) with thermal burn injuries affecting ≥5% of total body surface area (TBSA). Patients were categorized into younger (18–59 years) and older (≥60 years) adults and further stratified based on the presence or absence of sepsis. Serum levels of 9 organ function markers and 19 inflammatory cytokines were measured at multiple time points during hospitalization and compared between patients with and without prior sepsis in both age groups. A repeated measures longitudinal regression analysis accounting for time was conducted to compare biomarker levels before and after sepsis onset, assessing their prognostic potential. Analyses adjusted for age, sex, TBSA, and days post-injury.

Results: A total of 1,331 patients (997 younger; 334 older) were included. Sepsis significantly increased alkaline phosphatase (ALP), creatine kinase (CK), urea, and pH (p<0.001 for all) in all patients, while glucose and bilirubin levels decreased (p<0.001 and p=0.025, respectively). Among younger adults, sepsis significantly elevated ALP, CK, urea, and pH, while reducing creatinine, glucose, and bilirubin (p<0.001 for all). In older adults, sepsis increased ALP, CK, urea (p<0.001 for all), and pH (p=0.027) but also elevated creatinine (p<0.001), contrasting with the adult results. Inflammatory cytokine analysis revealed that sepsis decreased IL-6 (p<0.001) and MCP-10 (p<0.001) while increasing TNF-α (p<0.01) across all patients. Younger adults showed reductions in IL-6 (p<0.001), IL-15 (p<0.05), and MCP-10 (p<0.001) with an increase in TNF-α (p<0.05), whereas older adults exhibited increases in IL-1α (p<0.05) and IL-8 (p<0.05). Conclusions: This study demonstrates the longitudinal impact of sepsis on various biomarkers overtime, highlighting those with predictive potential for aiding diagnosis. It also examines how biomarker levels change from pre- to post-sepsis, providing insights into its progression. Age-specific differences highlight the need for tailored diagnostic approaches.

Ascariasis during corrective Roux-en-Y hepaticojejunostomy.

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Authors:
Cristina Botero Fonnegra, Kedar Sukharamwala, Prashant Sukharamwala, Samarth Patel, Subhasis Misra

Body of Abstract:
Background

Ascaris spp. is a parasitic nematode whose eggs can remain viable in the environment for extended periods. Ascariasis, the infection caused by Ascaris spp., occurs when individuals ingest these eggs. Over 1 billion people are affected worldwide. In developed nations, however, sporadic cases are often linked to individuals who have traveled to regions where the infection is endemic. The infection can be asymptomatic or present with gastrointestinal symptoms, bowel obstruction, or biliary disorders due to the migration of the parasite through the small bowel. The number of cases in the United States has been increasing, particularly in southeastern regions, due to travel, immigration, and climate conditions that favor the survival of the parasite.

Case presentation

The patient was a 22-year-old woman who initially presented with symptomatic cholelithiasis at an outside institution, where she underwent a laparoscopic cholecystectomy. Her medical history was significant for recent immigration from Polynesia. She was subsequently discharged but re-presented with abdominal pain 7 days later. A CT scan revealed a biliary leak, and an ERCP identified a bile duct injury, with no other significant imaging findings. She was transferred to our tertiary care facility for corrective Roux-en-Y hepaticojejunostomy. During intraoperative inspection of her small bowel, numerous cord-like structures were palpated, suggesting a parasitic infection.
Given the clinical suspicion of an intestinal helminth infection, a decision was made to perform an enterotomy to extract the parasites, which were milked from the ligament of Treitz to the terminal ileum (Figure 1). Gross examination, along with subsequent microbiological and pathological analysis, confirmed the presence of Ascaris lumbricoides. The patient was treated with albendazole during her stay, and a follow-up stool antigen test was negative, confirming the eradication of the infection. The patient recovered well postoperatively.

Conclusion
This case presents an unexpected and significant intraoperative finding that was not evident preoperatively, despite the use of preoperative imaging. The successful identification and management of this patient underscores the importance of heightened clinical vigilance for parasitic infections in patients with a history of travel to high-endemic areas.

The Use Of A Novel Microbicidal Liquid Polymer (Preventogen) To Reduce Tunneled Hemodialysis Catheters Infections In Patients Receiving Hemodialysis

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Authors:
Brett Hazuka, Julie Morris, Samir Awad

Body of Abstract:
Background: Catheter related bloodstream infections (CRBSI) from the use of tunneled hemodialysis catheters (THDC) are reported to be 1.1 to 6.1 episodes per 1000 catheter days and are associated with increased morbidity, hospitalization, and death. Standard of care (SOC) of the catheter exit site (ES) include various dressings such as Coversite, Tegaderm and Biopatch/CHG, which are currently used to reduce ES infections and decrease CRBSI, have had no significant impact on CRBSI rates. Preventogen, a novel microbicidal Liquid Polymer, which on drying forms an occlusive elastomeric barrier around the THDC at the ES has been shown to actively kill pathogens such as MDRO and Non-MDRO gram positive & negative bacteria, and various fungi on contact through cell lysis. Our objective was to evaluate the impact of Preventogen, on catheter site infection rates. We hypothesized that the use of Preventogen will protect patients undergoing dialysis with THDC against bacterial and fungal infections.
Methods: Under an IRB approved protocol, a retrospective review of a prospective data base of patients that had de novo THDC placement for HD at three dialysis centers was performed from 6-1-24 to 12-11-24. For each patient, Preventogen was applied for 1 inch around the tunneled hemodialysis catheter at the insertion site and catheter during placement and reapplied weekly thereafter at HD session for a total period of 180 days or until an ES infection or CRBSI developed. Age, gender, race, comorbidities (HTN, CHF, DM, Tobacco, ETOH use, Cirrhosis, Cancer, Obesity, Anticoagulation), CKD stage, insertion site, type of catheter, catheter days, ES infections and CRBSIs were collected. ES infection and CRBSI rates were calculated as number of infections per 1000 catheter days and compared to historical documented rates using SOC dressings.
Results: To date, 38 out of 60 patients have been enrolled. All patients were >= CKD 3 stage. The median age was 59 yo, 20(53%) were Males, 21(55%) White, 15(40%) Black, 2(5%) Other. Comorbidities included 26(68%) HTN, 18(47%) ETOH use, 14(37%) Smokers, 14(37%) Obese (BMI>30), 14(37%) on Anticoagulation, 12(36%) Diabetic, 10(26%) CHF, 9(24%) Cirrhotic, and 7(18%) Cancer. The IJ site was used in 34(89%). THDCs inserted were all polyurethane. Over the study period with 4090 catheter days there were no CRBSIs, and one (2.6%) catheter exchanged due to a suspected ES site infection with cultures demonstrating no growth. In contrast, historical data collected at the same dialysis centers demonstrated that 5.2% (33 of 637) of THDC were removed secondary to infection.
Conclusion: Given the reported ES infection rate of 4.1 per 1000 catheter days and CRBSI of 4.5 per 1000 catheter days, in this ongoing study, preliminary results demonstrate that the use of Preventogen liquid polymer as a dressing for THDC was safe with no documented ES infections and no cases of CRBSI over 4090 catheter days. Further study is ongoing.

Impact of Donor Microbiota on the Efficacy of Fecal Microbiota Transplantation in a Mouse Model of Lethal Bacterial Infection

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Authors:
Andrew Benjamin, Ellen Cohn, Jessica Cao, John Alverdy, Olga Zaborina, Rebecca Meltzer, Robert Keskey

Body of Abstract:
Background: A western diet (WD) that is high in fat and low in fiber negatively affects the composition and function of the gut microbiota and has been implicated in a number of poor outcomes following both surgical and infectious stress. We have demonstrated that mice consuming WD experience alterations in their gut microbiota with decreased diversity and reduced metabolite production that are associated with increased mortality when compared to a low fat, high fiber, standard chow diet (SD). Furthermore, we demonstrated that a fecal microbiota transplant (FMT) from an SD FMT donor can rescue an SD recipient from lethal bacterial peritonitis. However, it remains unclear the extent to which the quality of the donor and recipient microbiota impact the efficacy of FMT rescue from lethal infection.

Hypothesis: We hypothesized that dietary induced changes to the FMT donor microbiota impact the ability of FMT to rescue mice from lethal infection, independent of the microbiota of the recipient.

Methods: C57BL/6 male mice were maintained on the following diets varying in fat and fiber composition for 6 weeks prior to the experiment: a standard diet (SD, 18% fat and 18% fiber), western diet (WD, 60% fat and no fiber), and high fat/high fiber diet (HFHF, 45% fat and 30% fiber). An FMT was prepared by sacrificing a healthy littermate and resuspending the cecal contents in sterile saline, using donors from each diet (SD-FMT, WD-FMT, and HFHF-FMT). Infection-related survival was assessed using an established murine model of lethal bacterial infection with intraperitoneal (IP) injection of Serratia marcescens (Sm). Approximately 1mL of FMT was delivered to each mouse via enema at the time of IP Sm and mice were monitored for 24 hours to determine survival. Cecal contents and serum were collected for 16S rRNA sequencing and metabolomics at time of sacrifice.

Results: An SD-FMT delivered to an SD recipient significantly increased gut tryptophan, short chain fatty acids, and indole metabolites without impacting microbiota composition. SD-FMT was associated with significantly reduced disease severity, as seen by lower sepsis scores and higher temperatures, and improved survival in both SD (100% survival with FMT vs 20% without) and WD (75% survival with FMT vs 25% without) recipients (n=5 per group, p=0.011). WD-FMT failed to rescue both SD and WD recipients (n=5 per group, p=0.7). The addition of dietary fiber to a high fat diet (HFHF-FMT) alone was not sufficient to improve survival following IP Sm, indicating that both dietary fat and fiber content are important in shaping an FMT donor microbiota capable of rescuing mice from lethal infection.

Conclusions: FMT results in significant functional changes to the gut microbiota and can rescue mice from lethal bacteria peritonitis, in a manner which is dependent on the FMT donor microbiota, but independent of the recipient. High fat diet-induced changes to the FMT donor microbiota negate this rescue effect.

Against Medical Advice but Not Infection: The Readmission Ramifications of Leaving AMA after Trauma Care.

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Authors:
Fabiana C Sanchez, Grace M Niziolek, Grant V Bochicchio, Jason A Snyder, Leonardo J Diaz Gandica, Lindsay M Kranker, Marco J Henriquez, Marguerite W Spruce, Melissa Canas, Michael W Alchaer, Ricardo A Fonseca

Body of Abstract:
Background:
Trauma patients who leave the hospital against medical advice (AMA) are at higher risk of adverse outcomes, including hospital readmission. Infection-related readmissions may be driven by incomplete treatment, missed follow-up care, or limited access to outpatient resources. This study compares infection-related readmission rates in trauma patients that left AMA versus those discharged per standard hospital protocol.
Methods:
We conducted a retrospective cohort study using data from an urban Level 1 trauma registry from 2018 to 2022. The study population included trauma patients with an Injury Severity Score (ISS) greater than or equal to 9 who resided within the four counties surrounding our institution. Patients who died during the index hospitalization or were discharged to hospice were excluded. Patients were categorized into those who left against medical advice (AMA) and those who underwent standard discharge (non-AMA). The primary outcome was infection-related readmission (IRR). Data collected included patient demographics, mechanism of injury (MOI), ISS, culture results, antibiotic usage, and length of stay. Statistical analyses conducted included t-tests, chi-square tests, and binary logistic regression.
Results:
Among the 5,845 trauma patients, 130 (2.2%) left against medical advice (AMA), and 5,715 (97.8%) were discharged under standard care (non-AMA). AMA patients were more likely to be male (84.6% vs 61.7%, p < 0.001), younger (40.9 years vs 53.0 years, p < 0.001), Black non-Hispanic (66.2% vs 47.6%, p < 0.001), and injured by a penetrating mechanism (33.8% vs 21%, p < 0.001). A total of 213 patients (3.6%) were readmitted within 30 days; patients who left AMA had an overall 30-day readmission rate that was fivefold higher than the non-AMA trauma population (16.9% vs. 3.3%, p < 0.001). A total of 90 patients were readmitted due to infection (1.5%, 9 AMA vs 81 non-AMA). The infection-related readmission rate was significantly higher in the AMA group compared to those discharged non-AMA (6.9% [9/130] vs 1.4% [81/5715], p <0.001). Logistic regression showed that leaving AMA was a significant predictor of readmission due to infection (OR = 4.592, 95% CI: 2.202–9.576, p < 0.001). Conclusions: Leaving the hospital AMA is an independent predictor of readmission due to infection after controlling for sex, age, race/ethnicity, and social vulnerability. This underscores the need for targeted interventions and closer follow-up for this high-risk group to reduce infection-related readmissions, especially among those with a penetrating mechanism of injury. Further research is needed to stratify the patient’s reason for leaving AMA to reduce the associated risk of adverse outcomes incurred by patients.

Evaluating the Management of Perforated Peptic Ulcers in CHUK, Rwanda: Insights into Short-Term Clinical Outcomes

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Authors:
Christophe MPIRIMBANYI, Miguel GASAKURE

Body of Abstract:
Background
Peptic ulcer perforation (PPU) remains a significant cause of morbidity and mortality globally, particularly in low- and middle-income countries (LMICs). Despite a decline in peptic ulcer disease incidence, PPU persists and is usually associated with higher morbidity and mortality. Despite that, there is still very limited data existing on PPU’s epidemiological and clinical characteristics as well as its management in Rwanda. Therefore, exhaustive clinical research would help to investigate this crucial matter further.
Methods
It was a retrospective cross-sectional study conducted only on adult patients diagnosed with PPU at the University Teaching Hospital of Kigali, Rwanda, between September 2022 and September 2023. Those patients were admitted and always followed by the General Surgery team. The data collection focused on demographics, clinical presentation, surgical management, postoperative complications, and outcomes were collected and then analyzed.
Results
The study involved 46 cases in total. It included predominantly male patients (80.5%) with a mean age of 36.8 years. The majority came from urban areas and had medical insurance. The intraoperative findings revealed the perforations occurring more predominantly in the prepyloric region (95.56%) and only around 4 % were found in the duodenal region.
All the cases were managed surgically. The surgical approaches of predilection were the Modified Graham patch (95.5%) or the primary repair (4.4%). Although most patients had no complications (75.5%), the most common postoperative complications were fever of unknown origin (13.3%), pneumonia (8.8%), and surgical site infection (4.4%). While most patients had uncomplicated postoperative courses, a 10% overall mortality rate was observed.
The average length of hospital stay was estimated at 6.67 days, with a standard deviation of 6.21 days. The range of hospital stays varied from 0 to 36 days. Only 8.6% were admitted to ICU and only 1 case had to be reoperated but no significant predictors for ICU admission or complications were identified.
Conclusions
This study highlights the burden of PPU in the biggest Teaching Hospital in Rwanda, CHUK. It emphasizes the need for early recognition, improved prevention, and management strategies for PPU. The high mortality rate underscores the critical nature of PPU. It also highlights the need to introduce new surgical approaches such as laparoscopic procedures. Further research is warranted, such as conducting a multi-center prospective study. This could help elucidate specific risk factors and optimize PPU treatment guidelines in Rwanda and in LMICs in general.

Time Matters: Early Video-Assisted Thoracoscopic Surgery Reduces the Risk of Post-Operative Empyema in Patients with Thoracic Trauma

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Authors:
Fabiana C Sanchez, Grace M Niziolek, Grant V Bochicchio, Jason A Snyder, Leonardo J Diaz Gandica, Lindsay M Kranker, Marco J Henriquez, Marguerite W Spruce, Melissa Canas, Michael W Alchaer, Ricardo A Fonseca

Body of Abstract:
Background:
Despite having a low incidence in the adult trauma population, empyema remains a serious infectious complication with multiple etiologies and risk factors. Early Video-Assisted Thoracoscopic Surgery (VATS) may reduce the risk of empyema by facilitating early drainage and preventing infection progression. This study compares the incidence of post-operative empyema in trauma patients undergoing early versus late VATS, aiming to assess the impact of timing on the risk of developing an empyema.
Methods:
This study was conducted using an urban level 1 trauma registry, querying all patients with thoracic trauma who underwent VATS from May 2018 to June 2024. We included patients who underwent VATS for retained hemothorax or lung entrapment. Patients undergoing VATS for pre-existing empyema, bleeding control, diaphragmatic injuries, or rib plating alone were excluded. Early VATS was defined as surgery performed within 4 days of admission; a cut point utilized in the EAST hemothorax guidelines. Post-operative empyema development was confirmed by imaging evidence, clinical evaluation, and/or microbiology findings. Comparative analyses were conducted using chi-square tests and independent samples t-test; a multivariate regression model was used to assess the risk of empyema controlling for penetrating injuries, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS) Chest score, chest tube placement after 24 hours from admission, retained hemothorax, non-chest surgeries before VATS, and VATS timing.
Results:
A total of 87 patients were identified, with 34 (39.1%) undergoing early VATS and 53 (60.9%) undergoing late VATS. Post-operative empyema was identified in 3 (8.8%) patients in the early VATS group compared to 19 (35.8%) in the late VATS group (p=0.005). The early and late VATS groups had statistically-similar age, gender, race, BMI, and ISS. Patients in the early VATS group had higher AIS chest scores (3.0 vs 2.7, p=0.013) and fewer ventilator days (5.5 vs 6.5, p<0.001) than the late group. Early VATS was also associated with a shorter hospital length of stay (12.8 vs 21.9, p=0.001). The late VATS group exhibited a trend toward higher conversion to open thoracotomy (9.4 vs 2.9%, p=0.244). Multivariate logistic regression analysis demonstrated that late VATS independently increases the risk of empyema (OR=6.099, p=0.011, 95% CI:1.51–24.67). Conclusions: In trauma patients with thoracic injuries, early VATS intervention (≤4 days) is associated with better clinical outcomes, including a significantly lower incidence of empyema, fewer ventilator days, and shorter hospital stays when compared to late VATS. These findings highlight the potential benefits of timely surgical management in thoracic trauma, particularly for post-traumatic retained hemothorax. However, further prospective studies are needed to determine whether these associations reflect causation or correlation.

Prodromal Phase of Infection Associated with Hypocoagulability, Acute Phase with Hypercoagulability based on Thromboelastography and Platelet Mapping

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Authors:
Aseal Liqa, Conor Dillon, Hassan Nadeem, Meredith Essandoh, Monica Patten, Robert Sawyer, Tjasa Hranjec

Body of Abstract:
Background: Infected patients are considered to be hypercoagulable.  We hypothesized that coagulopathy associated with infection would be measurable by Thromboelastography with Platelet Mapping (TEG-PM).  

Methods:  A single center, chart review identified adult, trauma patients, admitted to our Trauma Intensive Care Unit (ICU) with hospital length of stay (LOS) ≥7 days, diagnosis of anemia of critical illness and evaluation of coagulopathy via TEG-PM before (prodrome phase – prior to diagnosis) and after (acute phase – following institution of treatment) the infectious work-up, over a 12-month period. Patients on continuous reno-renal replacement and full anticoagulation were excluded.  Univariate analysis was used to evaluate change in coagulation parameters between prodromal and acute phase of infection based on paired sample testing.    

Results: A total of 20 patients underwent coagulopathy evaluation via TEG-PM in the setting of anemia of critical illness.   Patients were mostly male (65%), with mean age 43±4 years, mean length of stay of 29.1±3.3 days, all with diagnosis of infection.  Thromboprophylaxis was initiated in 80% of the patients, with mean anti-Xa 0.19±0.1; due to progressive anemia, enoxaparin was held in 20% of the patients.  TEG-PM was collected in 20 patients during the prodromal phase, mean 0±0.5 days surrounding the infectious work-up; 16 received evaluation of coagulopathy during the acute phase with mean 3.9±0.7 days surrounding the infectious work-up.  Acute phase was associated with hypercoagulable TEG parameters (Table 1).  During the prodromal phase, however, R parameter displayed significant hypocoagulability.  Platelet activity, specifically MA-AA, and fibrinogen (CFF) increased during the prodromal phase, but MA remained within normal limits.  Lysis was non-contributory. Patients received a total of 150 red blood cell (RBC) transfusions, mean 6.6±1.6 units per patient, range 1-30.  Forty percent of the patients had an identifiable bleeding source (gastrointestinal, retroperitoneal, hemoptysis) at the time of the prodromal phrase, requiring extensive diagnostic and therapeutic interventions and active resuscitation.  Three patients developed deep venous thrombosis (DVT), diagnosed 4.3±1.3 days after infectious work-up (acute phase).  

Conclusion: Acute phase of infection is associated with hypercoagulable state, as diagnosed by TEG-PM, and may lead to DVT formation.  Surprisingly, prodromal phase, when signs and symptoms of infection may be overlooked and attributed to other causes, TEG-PM shows hypocoagulability, that may lead to significant bleeding necessitating active resuscitation and transfusion.  TEG-PM may be a useful adjunct in infectious diagnosis during the prodromal phase.

Is Social Vulnerability Associated with Surgical Site Infections in Trauma Patients?

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Authors:
Lillian S Kao, Mokunfayo Fajemisin, Renee W, Green, Stephanie Martinez Ugarte, William Rieger

Body of Abstract:
Background: High social vulnerability, which integrates multiple indicators of social determinants of health, has been shown to be associated with increased trauma mortality and recurrent injuries. We hypothesized that social vulnerability, as measured by the Area Deprivation Index (ADI) is associated with an increased risk of surgical site infections (SSIs).

Methods: A retrospective cohort study was performed of trauma patients undergoing laparotomy procedures, age greater than 16, surviving greater than 48 hours, presenting to a single urban Level 1 trauma center from 2020 to 2021. Demographics, injury details, operative information and postoperative infectious outcomes were obtained from the trauma registry and supplemented by chart review. Social vulnerability was assessed using ADI which utilizes census-tract level information. The ADI has a maximum score of 100 and scores closer to 100 indicate increased social vulnerability. Outcomes of interest were organ-space surgical site infections (O-SSI), or any type of SSI associated with the trauma laparotomy. SSIs were classified per CDC definitions. Univariate and multivariable analyses were performed adjusting for age, gender, trauma mechanism, colonic injury, damage control laparotomy, and injury severity score (ISS).

Results: Among the 357 trauma patients undergoing laparotomy, the median age was 34.0 (IQR 11-57), and median ISS 22.0 (IQR 1-43.0). The majority of patients had a penetrating injury mechanism (57%) and were male (80%). Sixteen percent of patients underwent a damage control laparotomy, and 33% had a colonic injury. The median ADI was 65.0 (IQR 32- 98). Seventeen percent of patients (n=60) had OS-SSI and 19% (n=69) had any SSI. On univariate analysis, ADI was not associated with OS-SSI or any SSI. Similarly, on multivariable analysis, ADI was not associated with OS-SSI (OR 1.09, 95% 0.76-1.15, p=0.39) or any SSI (OR 1.01, 95% CI 0.92-1.06, p=0.71).

Conclusion: Social vulnerability, as defined by ADI, was not associated with OS-SSI or any SSI after trauma laparotomy. Injury characteristics and patient physiology may have more impact than social factors on SSIs after emergency trauma laparotomy. Additionally, more granular measures of social determinants of health may be needed to better elucidate any associations. Further research is needed in larger and less urban populations to determine if social vulnerability is associated with SSIs or affects any mediating factors such as time to source control.

Pathogen-induced coagulopathy: the role of pathogen-derived virulence factors in the development of clinically significant coagulopathy

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Authors:
Andrew Benjamin, Ellen Cohn, Jessica Cao, John Alverdy, Olga Zaborina, Rebecca Meltzer, Robert Keskey

Body of Abstract:
Background: Trauma-induced coagulopathy (TIC) results in significant morbidity and mortality despite improved understanding of specific TIC phenotypes that occur after injury. While individual patient factors (sex, genetics, injury severity, etc.) can influence a patient’s coagulation profile, there remains poorly understood within-group differences. Life-threatening injury requiring surgery, antibiotics, and prolonged hospitalization often predisposes trauma patients to colonization by pathogenic bacteria (i.e. Pseudomonas aeruginosa), but current TIC research focuses almost exclusively on host factors. Host-pathogen interactions may play an underappreciated role in the development of coagulopathy, given the intricate interplay between infection, inflammation, and coagulation. Bacterial pathogens are known to produce virulence factors that degrade key components of the clotting cascade as a strategy for subverting the host immune system, but the extent to which these mechanisms contribute to clinically significant coagulopathy remains unclear.

Hypothesis: We hypothesize that Pseudomonas aeruginosa has the capacity to induce clinically significant coagulopathy via secreted virulence factors.

Methods: Pseudomonas aeruginosa (Pa) isolated from an ICU patient was grown in liquid media. Supernatant (Pa-sup) was collected at stationary phase, filtered, and added to citrate-anticoagulated whole blood from 5 healthy, human volunteers at 1:10 and 1:15 dilutions and compared to the addition of liquid media alone (Ctrl). Coagulation profiles were analyzed using the ROTEM sigma (Werfen), a functional assay of the intrinsic (int)/extrinsic (ext) clotting cascade and fibrin contribution to clot formation. Also, collagenolytic activity of Pa-sup was assessed in vitro using fluorescein-conjugated gelatin (Invitrogen).

Results: Pa-sup caused significant coagulopathy in both the intrinsic and extrinsic clotting cascades in a dose-dependent manner. Pa-sup significantly decreased maximum clot firmness (MCF) (MCFint: 10.2 vs 26.7 vs 53.4; 1:10 vs 1:15 vs Ctrl; p<0.001 | MCFext: 17.6 vs 39.7 vs 58.5; 1:10 vs 1:15 vs Ctrl; p<0.001) and amplitude at 10 minutes (A10) (A10int: 4.8 vs 24.3 vs 49.1; 1:10 vs 1:15 vs Ctrl; p<0.001 | A10ext: 16.4 vs 34.2 vs 51.7; 1:10 vs 1:15 vs Ctrl; p<0.001). Additionally, 1:10 Pa-sup caused a significant increase in clotting time (CT) (CTint: 438.2s vs 168.1s Ctrl; p<0.001 | CText: 191.2s vs 61.1s Ctrl p=0.06). Pa-sup-induced coagulopathy correlated with increased collagenolytic activity. Conclusion: Pseudomonas aeruginosa yields exoproducts that more than double clotting time and weaken clot strength by almost 50%. Taken together, these data demonstrate that certain pathogens can secrete virulence factors that cause clinically significant coagulopathy. Further work is ongoing to determine the extent to which pathogen-induced coagulopathy is amplified in the setting of trauma and to determine its generalizability to other pathogens.