Infection Type and Class: Exploring Thrombotic and Renal Complications in a SICU Cohort

Authors:
Ioannis Karikis, Yasmin Arda, John O. Hwabejire, Michael P. DeWane, Casey M. Luckhurst, Lydia Maurer, Joshua S. Ng-Kamstra, Haytham M. Kaafarani, George C. Velmahos, Galit H. Frydman

Body of Abstract:
Background:
 Infection-related thrombosis and organ injury are increasingly recognized in critically ill patients. Surgical ICU (SICU) patients may be particularly vulnerable because they combine severe physiological stress, complex operations, and high rates of invasive devices and broad-spectrum antimicrobials. We aimed to examine how pathogen burden and diversity relate to clinically significant adverse events in SICU patients with suspected infection. 

Methods:
 We conducted a single-center retrospective study of 137 SICU patients with suspected infection and available microbiologic data, who underwent longitudinal microbiologic sampling from 2020-2024. Organisms were grouped into four pathogen classes (Gram-positive bacteria, Gram-negative bacteria, fungi, and viruses). For each patient, we derived (1) the number of pathogen classes involved (0–4), (2) the number of distinct bacterial isolates (0, 1, 2–3, ≥4), and (3) combinations of bacteria, fungi, and viruses. The primary outcome was a major thrombotic event (deep venous thrombosis, pulmonary embolism, line thrombosis, myocardial infarction, or stroke). Secondary outcomes were AKI and hospital LOS. Associations were evaluated descriptively with univariate analysis.

Results:
 Median age was 63 (51–73) years and median hospital LOS 12 (6–25) days. Overall, 22/137 patients (16%) developed an MTE and 41/132 (31%) developed AKI. Across pathogen-class strata (N=132 with complete data), MTE rates rose from 1/44 (2.3%) with no detected class to 5/15 (33.3%) with three classes and 4/5 (80.0%) with all four classes involved (p<0.001); AKI showed a similar pattern (13.6%, 19.5%, 51.9%, 60.0%, and 80.0%, respectively; p<0.001). Median LOS increased from 12 (5.5–22.5) days with no pathogen class to 23.5 (11–30) days with three classes and 60 (50–96.5) days with all four classes (p=0.003). When stratified by bacterial isolates, MTE rose from 4/80 (5.0%) with no bacterial growth to 6/20 (30.0%) with ≥4 isolates, and AKI from 14/80 (17.5%) to 8/15 (53.3%) (both p<0.001), with LOS increasing from 8.5 (5–18) to 29 (14–54) days (p=0.002). The highest rates of MTE and AKI were observed in a small subgroup with concurrent bacteria, fungi, and viruses (57.1% and 85.7%, respectively). Conclusions:  In this SICU cohort, increasing pathogen burden and diversity were associated with higher rates of clinically significant adverse events, including major thrombotic events, AKI, and prolonged hospitalization in a graded fashion. A plausible explanation for these patterns is an underlying immunothrombotic process linking infection, thrombosis, and organ injury. These hypothesis-generating findings support larger studies to clarify causal pathways and to test strategies to prevent complications in high-risk surgical ICU patients, such as combinatorial and/or amplifying inflammatory pathways secondary to multimodal infectious stimuli.

Infectious Complications After Surgical Stabilization of Rib Fractures: A National Analysis

Authors:
Hadi Hamdan, Ahmad El Nouiri, Camden Gardner, Tarek Araji, Michael Bock, Jeffrey Johnson

Body of Abstract:
Background: Surgical stabilization of rib fractures (SSRF) has gained increasing traction for the management of severe chest wall injuries. Prior national studies have focused on mortality and pulmonary outcomes, while infectious complications are only reported as secondary endpoints. Thus, the relationship between SSRF and nosocomial infections are poorly understood. We aimed to evaluate the association between SSRF and major hospital-acquired infections using a contemporary national trauma cohort.

Methods: A retrospective analysis of adult trauma patients with ≥1 rib fracture was conducted using ACS-TQIP (2019–2023). ICD-10 diagnosis and procedure codes identified rib fractures and SSRF cases. Patients were categorized as to whether they underwent SSRF vs. non-operative management (NOM). Multivariable logistic regression evaluated associations of both interventions with severe sepsis, catheter-associated urinary tract infection (CAUTI), and central line–associated bloodstream infection (CLABSI). Adjustment for demographics, comorbidities, physiology, injury severity (ISS, GCS, shock index), antibiotic therapy, hospital length of stay, ICU length of stay, ventilator days, and hospital characteristics was done. A planned sub-analysis—restricted to mechanically ventilated, ICU-admitted patients—assessed ventilator-associated pneumonia (VAP).

Results: Among 595,375 eligible patients, 18,140 (3.0%) underwent SSRF. Median time to surgery was 4 days (IQR 3–8). SSRF patients had greater critical-care exposure, including longer ICU stay (7 days, IQR 4–13 vs. 4 days, IQR 2–7) and ventilator duration (7 days, IQR 3–13 vs. 4 days, IQR 2–10). Unadjusted rates of severe sepsis (1.66% vs. 0.53%), CAUTI (0.41% vs. 0.21%), CLABSI (0.14% vs. 0.06%), and VAP (3.34% vs. 0.86%) were all higher among SSRF patients. After full adjustment, SSRF remained independently associated with severe sepsis (aOR 1.87, p<0.001). SSRF was not independently associated with CAUTI (aOR 1.25, p=0.067) or CLABSI (aOR 1.50, p=0.063). In the ventilated ICU sub-analysis (94,842 patients), SSRF remained independently associated with increased VAP risk (aOR 1.44, p<0.001) after adjustment. Conclusion: In a large national cohort, SSRF was associated with increased odds of severe sepsis and VAP despite adjustment for comorbidities, physiology, injury severity, and critical-care exposure. SSRF was not independently associated with an increase in CAUTI or CLABSI risk. The persistence of the VAP association suggests that factors intrinsic to patients selected for SSRF—such as injury complexity or clinical trajectory—may contribute to this elevated vulnerability. Further work is needed to clarify whether these risks reflect operative factors, patient selection, or underlying injury patterns.

Inflammatory Dysregulation and Persistent Epigenetic Modifications of A20 in Necrotizing Enterocolitis

Authors:
Heather Grubbs, Christopher Luschen, Catherine Hunter

Body of Abstract:
Background

The pathogenesis of necrotizing enterocolitis (NEC) centers on dysregulation of inflammation, intestinal barrier function, and cell death. A20 is an inflammatory cascade-suppressing protein which we hypothesize is decreased in active NEC. Additionally, we hypothesize that decreased expression is maintained following recovery due to epigenetic modifications of the TNFAIP3 gene promoter region which encodes for A20. 

 

Methods

Intestinal tissue from neonates with active NEC, following NEC recovery, or without NEC was snap frozen. RNA was extracted for RT-qPCR analysis of TNFAIP3 expression. DNA was also extracted and underwent bisulfite conversion followed by PCR amplification of the TNFAIP3 promoter region and sanger sequencing. Site-specific methylation percentage was then calculated in the TNFAIP3 promoter region. Statistical significance was determined with ANOVA.   

 

Results

            Intestinal tissue from patients with no history of NEC had elevated A20 expression compared to active and recovered tissue (p=0.0039 and p=0.0009, respectively). Additionally, there was no difference in expression between expression in active and recovered tissue (p=0.9063). Three methylation sites were identified in the TNFAIP3 promoter region at positions -115, -26, and -5 from gene start with higher percent methylation in active and recovered NEC compared to controls (p=0.0006 and p=0.0005, respectively). No difference was found between active and recovered NEC percent methylation (p=0.9755).

 

Conclusions

            The inflammatory regulator A20 was found to have decreased expression in NEC and recovered NEC tissue compared to control, emphasizing the dysregulated inflammatory response seen in NEC. Additionally, the promoter region of the TNFAIP3 gene was found to have significantly higher percent methylation at three sites in recovered and active NEC tissue compared to control. Therefore, epigenetic modifications seen in both active and recovered NEC tissue may be associated with decreased transcription of A20 and therefore impaired inflammatory regulation in NEC which persists following recovery.

Intraoperative Particulate Matter Exposure and Surgical Site Infection Risk in Cardiac Surgery: A Prospective Feasibility Study

Authors:
Oluwaseun Adeyemi, Divya Kewalramani, Justin Benton, Gediminas Mainelis, Philip Barie, Mayur Narayan

Body of Abstract:
Despite decades of investment in operating room ventilation systems, surgical site infections (SSIs) remain a major source of morbidity in clean cardiac procedures. While bacterial contamination of surgical wounds correlates with airborne particle concentrations, the relationship between quantified intraoperative particulate matter (PM) exposure and clinical SSI development remains uncharacterized. We hypothesized that patients who develop SSI following cardiac surgery encounter higher proportions of high-risk PM thresholds compared to patients without SSI, with phase-specific exposure patterns distinguishing infected from non-infected cases.

Methods: We prospectively enrolled 31 CABG patients with continuous intraoperative PM monitoring and 30-day SSI surveillance. PM was quantified by number concentration (NC: 0.3–0.5, 0.5–1.0, 1.0–2.5 µm) and mass (PM1.0, PM2.5). Operative phases were baseline (procedure start to cardiopulmonary bypass [CPB] initiation), prolonged electrocautery (CPB period), and closure (CPB termination to procedure end). High-risk PM exposure was defined as ≥2 standard deviations above baseline mean. We calculated the proportion of each phase exceeding high-risk thresholds and compared exposure patterns between SSI and non-SSI cohorts.

Results: Among 31 enrolled patients (mean age 65.5 ± 9.7 years, 90.3% male, mean BMI 29.1 ± 5.2 kg/m²), one patient (3.2%) developed deep sternal wound SSI requiring surgical debridement and prolonged antibiotic therapy. Median operative duration was 4.2 hours (IQR 3.8–4.9), with baseline, electrocautery, and closure phases comprising 18%, 64%, and 18% of total operative time, respectively. During the closure phase, the SSI case exhibited elevated PM exposure across all size fractions compared to non-SSI patients: PM2.5 exceeded high-risk thresholds for 8.3% versus 0.3% of phase duration (27.7-fold difference), PM1.0 for 8.0% versus 0.3% (26.7-fold), NC1.0–2.5 for 1.4% versus 0.1% (14-fold), NC0.5–1.0 for 8.3% versus 0.6% (13.8-fold), and NC0.3–0.5 for 8.3% versus 0.01% (830-fold). Mass-based PM metrics demonstrated more pronounced divergence than number concentrations, with PM2.5 and PM1.0 showing the largest absolute differences. During the prolonged electrocautery phase, the SSI case exhibited elevated exposure primarily in fine particle fractions: NC0.5–1.0 exceeded thresholds for 2.9% versus 0.2% of phase duration (14.5-fold difference) and NC0.3–0.5 for 3.0% versus 0.2% (15-fold). Temporal analysis revealed that 89% of high-risk PM excursions during closure occurred within 15 minutes preceding final skin approximation

Conclusion: This preliminary evidence demonstrates phase-specific PM exposure patterns distinguishing SSI from non-SSI cases, with closure phase exhibiting the strongest divergence. These findings establish technical feasibility for continuous, size-resolved PM monitoring and justify larger prospective studies examining PM exposure thresholds as modifiable SSI risk factors.

Dose-Dependent Effects of Whole Blood Transfusion on Associated Infection Risk in Trauma

Authors:
Hadi Hamdan, Ahmad El Nouiri, Camden Gardner, Drishti Lall, Kurt Kralovich, Jeffrey Johnson

Body of Abstract:
Background: Whole blood (WB) transfusion has emerged in trauma resuscitation as a method associated with improved survival over component therapy (CT), largely attributed to reduced hemorrhagic deaths. However, WB is a biologically complex fluid with distinct immunologic and volume-expanding properties that may affect infection risk differently than CT. Although infections have often been secondary outcomes in transfusion studies, their direct relationship with WB use remains unclear. We hypothesized that a higher WB-to-total-transfusion ratio would be associated with lower rates of nosocomial infection in a dose-dependent manner.

Methods: Adult trauma patients from the 2020–2023 national TQIP database who received transfusion were included. The WB ratio was defined as the proportion of total transfused volume given as WB. Outcomes were examined across the full ratio range (0–1), with extremes (CT-only vs WB-only) analyzed separately to confirm consistency. Variables significant on univariate analysis were entered into multivariable logistic regression models evaluating associations between WB ratio and infection outcomes: severe sepsis, surgical site infections, catheter-associated urinary tract infection (CAUTI), and central-line associated bloodstream infection (CLABSI). Models adjusted for demographics, physiology, injury severity, comorbidities, transfusion volume, and hospital characteristics. A subanalysis of ventilated ICU patients assessed ventilator-associated pneumonia (VAP), additionally adjusting for ICU stay and ventilator days.

Results: Among 221,142 transfused patients, 79.8% received CT only, 8.7% WB only, and 11.5% both. Increasing WB ratio was associated with lower odds of severe sepsis (aOR 0.82, p = 0.006), superficial SSI (aOR 0.79, p = 0.020), and CAUTI (aOR 0.73, p = 0.012). At the extremes, WB-only versus CT-only showed similar reductions in severe sepsis (aOR 0.74, p = 0.001), superficial SSI (aOR 0.73, p = 0.008), deep SSI (aOR 0.79, p = 0.028), organ/space SSI (aOR 0.65, p < 0.001), and CAUTI (aOR 0.73, p = 0.021), with no difference in CLABSI. In the ventilated ICU subanalysis (n = 94,206), higher WB ratio was associated with increased odds of VAP (aOR 1.21, p < 0.001), and this persisted when comparing WB-only to CT-only. Across models, older age, higher ISS, diabetes, steroid use, chemotherapy, and longer hospitalization remained independent infection predictors. Conclusion: Our findings demonstrate a consistent, dose-dependent protective association between increasing WB ratio and several nosocomial infections in trauma patients, an effect that remained stable at the extremes of transfusion practice (WB-only vs CT-only). However, this trend did not extend to ventilator-associated pneumonia, which increased with higher WB exposure. These results highlight a potentially heterogeneous effect of WB transfusion across infection types and support further study into the mechanisms and optimal transfusion balance.