Classification of trauma-related preventable death; protocol of a Delphi procedure.

BACKGROUND: Trauma-related (preventable) death is used to evaluate the management and quality of trauma care worldwide. Therefore, it is necessary to identify fatalities in the trauma care population and assess them on preventability. However, the definition on trauma-related preventable death lacks validity due to differences in terminology and classifications. This study aims to reach consensus on the definition of trauma-related preventable death by performing a Delphi procedure, thereby, improving the assessment of trauma-related preventable death and thereby enhancing the quality of trauma care. METHODS: Based on the results of a recently performed systematic review Hakkenbrak (2021). The definitions used to describe trauma-related preventable death could be divided into four categories: 1) Clinical definition based on panel review or expert opinion, 2) Trauma prediction algorithm, 3) Clinical definition with an additional trauma prediction algorithm and 4) Others (e.g., errors in care or detailed clinical definition). A three round, electronic Delphi study will be performed in the Netherlands to reach consensus. Experts from the department of Trauma surgery, Neurosurgery, Forensic medicine, Anaesthesiology and Emergency medicine, of the designated Level 1 trauma centres in the Netherlands, will be invited to participate. In the first round the panel will comment on the composed categories and trauma prediction algorithms. In the second and third round a feedback report will be presented and the questions with disagreement will be retested. DISCUSSION: The identification and assessment of trauma-related preventable death is necessary to evaluate and improve trauma care. Therefore, a valid, fair, and applicable definition of trauma-related preventable death is required. The Delphi technique is utilized to reach group consensus to obtain a scientifically valid definition of trauma-related preventable death.

Role of Brain Angiotensin-II in Development of Experimental Diabetic Nephropathy in Wistar Rats

Abstract The renin-angiotensin-aldosterone system (RAAS) plays a key role in diabetic nephropathy (DN). Angiotensin-II secreted during the RAAS pathway increases nephropathy. It stimulates oxidative stress which can quench nitric oxide. Reduced nitric oxide level aggravates Ang-II-induced vasoconstriction. Ang-II has also emerged as a central mediator of the glomerular hemodynamic changes that are associated with renal injury. Deletion of ACE2 is also noted due to increased Ang-II level which leads to the development of DN. We hypothesize that nephropathy caused by Ang-II in the periphery may be controlled by brain RAAS. ACE inhibitors and ARBs may show the renoprotective effect when administered through ICV without crossing the blood-brain barrier. DN was observed after 8 weeks of diabetes induction through alloxan. Administration of captopril and valsartan once and in combined therapy for 2 weeks, significantly reduced urine output, blood urea nitrogen, total protein in the urine, serum cholesterol, serum creatinine, serum triglycerides, and kidney/body weight ratio as compared to diabetic control rats. Further, combination therapy significantly increased the body weight and serum nitrate level as compared to diabetic control animals. However, increased ACE2 levels in the brain may reduce the sympathetic outflow and might have decreased the peripheral activity of Ang-II which shows beneficial effects in DN.

Development and clinical application of hydrogel formulations containing papain and urea for wound healing

Abstract Hydrogels are used for wound treatment, as they may contain one or more active components and protect the wound bed. Papain is one of the active substances that have been used with this purpose, alongside urea. In this paper, carboxypolymethylene hydrogels containing papain (2% and 10% concentrations) and urea (5% concentration) were produced. Physical-chemical stability was performed at 0, 7, 15 and 30 days at 2-8ºC, 25ºC and 40ºC, as well as the rheological aspects and proteolytic activity of papain by gel electrophoresis. Clinical efficacy of the formulations in patients with lower limb ulcers was also evaluated in a prospective, single-center, randomized, double-blind and comparative clinical trial. The results showed 7-day stability for the formulations under 25ºC, in addition to approximately 100% and 15% of protein activity for 10% and 2% papain hydrogel, respectively. The rheological profile was non-Newtonian for the 10% papain hydrogel tested. There were no significant differences regarding the mean time for healing of the lesions, although 10% papain presented a better approach to be used in all types of tissue present in the wound bed.

Morfología de las lesiones iatrogénicas de la vía biliar: aspectos diagnósticos y terapéuticos / Morphology of iatrogenic lesions of the bile duct: diagnostic and therapeutic options

RESUMEN: Las lesiones iatrogénicas de las vías biliares (LIVB), en el curso de una colecistectomía laparoscópica (CL), son complicaciones que causan resultados inesperados para cirujanos un incremento en los riesgos de los pacientes (morbilidad y mortalidad), afectando su calidad de vida. Asimismo, causan situaciones difíciles desde el punto de vista técnico para el cirujano que debe repararlas desde un punto de vista técnico. El objetivo de este manuscrito fue resumir la información referente a las LIVB y describir su morfología y opciones diagnóstico-terapéuticas.

SUMMARY: Iatrogenic Bile duct injuries (IBDI), during laparoscopic cholecystectomy (CL), are complications that cause unexpected results for surgeons, an increment in patient risks (morbidity and mortality), and affect the patient´s quality of life. At the same time, they create difficult situations for the repairing surgeon from a technical point of view. The aim of this manuscript was to summarize the information regarding IBDI and to describe its morphology and diagnostic-therapeutic options.

The derivation of an International Classification of Diseases, Tenth Revision-based trauma-related mortality model using machine learning.

BACKGROUND: Existing mortality prediction models have attempted to quantify injury burden following trauma-related admissions with the most notable being the Injury Severity Score (ISS). Although easy to calculate, it requires additional administrative coding. International Classification of Diseases (ICD)-based models such as the Trauma Mortality Prediction Model (TMPM-ICD10) circumvent these limitations, but they use linear modeling, which may not adequately capture the intricate relationships of injuries on mortality. Using ICD-10 coding and machine learning (ML) algorithms, the present study used the National Trauma Data Bank to develop mortality prediction models whose performance was compared with logistic regression, ISS, and TMPM-ICD10. METHODS: The 2015 to 2017 National Trauma Data Bank was used to identify adults following trauma-related admissions. Of 8,021 ICD-10 codes, injuries were categorized into 1,495 unique variables. The primary outcome was in-hospital mortality. eXtreme Gradient Boosting (XGBoost), a ML technique that uses iterations of decision trees, was used to develop mortality models. Model discrimination was compared with logistic regression, ISS, and TMPM-ICD10 using receiver operating characteristic curve and probabilistic accuracy with calibration curves. RESULTS: Of 1,611,063 patients, 54,870 (3.41%) experienced in-hospital mortality. Compared with those who survived, those who died more frequently suffered from penetrating trauma and had a greater number of injuries. The XGBoost model exhibited superior receiver operating characteristic curve (0.863 [95% confidence interval (CI), 0.862-0.864]) compared with logistic regression (0.845 [95% CI, 0.844-0.846]), ISS (0.828 [95% CI, 0.827-0.829]), and TMPM-ICD10 (0.861 [95% CI, 0.860-0.862]) (all p < 0.001). Importantly, the ML model also had significantly improved calibration compared with other methodologies (XGBoost, coefficient of determination (R2) = 0.993; logistic regression, R2 = 0.981; ISS, R2 = 0.649; TMPM-ICD10, R2 = 0.830). CONCLUSION: Machine learning models using XGBoost demonstrated superior performance and calibration compared with logistic regression, ISS, and TMPM-ICD10. Such approaches in quantifying injury severity may improve its utility in mortality prognostication, quality improvement, and trauma research. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; level III.

Aloe vera and wound healing: a brief review

Abstract Aloe vera possesses a great therapeutic importance in traditional medicine. It has attracted the attention of modern medical fields due to its wide pharmacological applications. The bioactive substances in Aloe vera proved to have antioxidant, anti-inflammatory, antibacterial, and antiviral properties. Taken into our consideration the long history of clinical applications of Aloe vera in traditional medicine, especially for promoting the healing of cutaneous wounds with rare adverse effects, it provides a cheap alternative to many expensive synthetic drugs. Recent techniques in tissue engineering created novel scaffolds based on Aloe gel extracts for wound healing applications. Nonetheless, further guided researche is required to foster the development of Aloe vera based scaffolds for the benefit of worldwide populations. Here, I systemically summarize the main events following wounding and the mechanism of action of Aloe vera in promoting the healing process. I hope to provide a solid piece of information that might be helpful for designing new research studies into this topic.

The effects of methanol extract of Galium verum L on cardiac redox state in hypertensive rats

Abstract The aim of this study was to assess the effects of methanol extract of G. verum on redox status of isolated heart of spontaneously hypertensive rats after ischemia. Twenty-four Wistar albino rats were divided into three groups: untreated control rats and rats that received 125 and 250 mg/kg G. verum extract for 4 weeks per os. Index of lipid peroxidation (measured as TBARS) and parameters of antioxidative defence system such as level of reduced glutathione (GSH) and activities of catalase (CAT) and superoxide dismutase (SOD) were spectrophotometrically determined in heart homogenate. The index of lipid peroxidation in heart tissue was lower in both treated groups compared to the control group. On the other hand, the activity of SOD was significantly higher after consumption of both doses, while the activity of CAT was significantly higher only after treatment with a higher dose of extract. Based on our results we might conclude that 4-week treatment with methanol extracts of G. verum has the potential to modulate myocardial redox signaling after ischemia, thus significantly alleviating cardiac oxidative stress and exerting dose-dependent antioxidant properties. Future studies are certainly necessary to fully clarify the role of this plant species in myocardial I-R injury.

Synthesis and characterization of chitosan-PVA hydrogel containing PEGylated recombinant epidermal growth factor on cell culture for wound healing substitute

Abstract The aim of the current study was to assess the physicochemical characteristics and wound healing activity of chitosan-polyvinyl alcohol (PVA) crosslinked hydrogel containing recombinant human epidermal growth factor (rh-EGF) or recombinant mouse epidermal growth factor (rm-EGF). The hydrogels were prepared and analyses were made of the morphological properties, viscosity, water absorption capacity, mechanical and bio-adhesive properties. The viscosity of the formulations varied between 14.400 - 48.500 cPs, with the greatest viscosity values determined in K2 formulation. F2 formulation showed the highest water absorption capacity. According to the studies of the mechanical properties, H2 formulation (0.153±0.018 N.mm) showed the greatest adhesiveness and E2 (0.245±0.001 mj/cm2) formulation, the highest bio-adhesion values. Hydrogels were cytocompatible considering in vitro cell viability values of over 76% on human keratinocyte cells (HaCaT, CVCL-0038) and of over 84% on human fibroblast cells (NIH 3T3, CRL-1658) used as a model cell line. According to the BrdU cell proliferation results, B1 (197.82±2.48%) formulation showed the greatest NIH 3T3 and C1 (167.43±5.89%) formulation exhibited the highest HaCaT cell proliferation ability. In addition, the scratch closure assay was performed to assess the wound healing efficiency of formulation and the results obtained in the study showed that F2 formulation including PEGylated rh-EGF had a highly effective role.

Development and Characterization of a Hydrogel Containing Silver Sulfadiazine for Antimicrobial Topical Applications. Part II: Stability, Cytotoxicity and Silver Release Patterns

Abstract Hydrogels are interesting for use in the treatment of topical wounds due to their virtually zero toxicity, and capacity for extended release of pharmaceuticals. Silver sulfadiazine (SSDZ) is the drug of choice in the treatment of skin burns. The aim of the study was to determine cytotoxicity, antimicrobial activity and stability of a PVA hydrogel with integrated silver sulfadiazine. SSDZ-hydrogels were prepared using 10% (w/w) PVA (either 89% or 99% hydrolyzed) and 1% (w/w) silver sulfadiazine. Cellular viability was assessed via MTS assays, antimicrobial activity via disk-diffusion and accelerated stability tests were carried out with analysis at 0, 30, 60, 90 and 180 days of storage at 40 ± 2 °C and a relative humidity of 75 ± 5%. The parameters evaluated included organoleptic characteristics, moisture, swelling ability, mechanical strength, FTIR, XRD, TGA and DSC, and silver release patterns via XRD and potentiometry. Cell viability tests indicated some cytotoxicity, although within acceptable levels. After 90 days of storage, SSDZ hydrogel samples exhibited a brown coloration, probably due to the formation of Ag or Ag2O nanoparticles. The SSDZ-loaded hydrogels suffered visual and physical changes; however, these changes did not compromise its use as occlusive wound dressings or its antimicrobial properties.

Whole blood resuscitation restores intestinal perfusion and influences gut microbiome diversity.

OBJECTIVE: Gut dysbiosis, an imbalance in the gut microbiome, occurs after trauma, which may be ameliorated with transfusion. We hypothesized that gut hypoperfusion following trauma causes dysbiosis and that whole blood (WB) resuscitation mitigates these effects. METHODS: Anesthetized rats underwent sham (S; laparotomy only, n = 6); multiple injuries (T; laparotomy, liver and skeletal muscle crush injuries, and femur fracture, n = 5); multiple injuries and 40% hemorrhage (H; n = 7); and multiple injuries, hemorrhage, and WB resuscitation (R; n = 7), which was given as 20% estimated blood volume from donor rats 1 hour posttrauma. Baseline cecal mesenteric tissue oxygen (O2) concentration was measured following laparotomy and at 1 hour and 2 hours posttrauma. Fecal samples were collected preinjury and at euthanasia (2 hours). 16S rRNA sequencing was performed on purified DNA, and diversity and phylogeny were analyzed with QIIME (Knight Lab, La Jolla, CA; Caporaso Lab, Flagstaff, AZ) using the Greengenes 16S rRNA database (operational taxonomic units; 97% similarity). α and ß diversities were estimated using observed species metrics. Permutational analysis of variance was performed for overall significance. RESULTS: In H rats, an average decline of 36% ± 3.6% was seen in the mesenteric O2 concentration at 1 hour without improvement by 2 hours postinjury, which was reversed following resuscitation at 2 hours postinjury (4.1% ± 3.1% difference from baseline). There was no change in tissue O2 concentration in the S or T rats. ß Diversity differed among groups for all measured indices except Bray-Curtis, with the spatial median of the S and R rats more similar compared with S and H rats (p < 0.05). While there was no difference in α diversity found among the groups, indices were significantly correlated with mesenteric O2 concentration. Members of the family Enterobacteriaceae were significantly enriched in only 2 hours. CONCLUSION: Mesenteric perfusion after trauma and hemorrhage is restored with WB resuscitation, which influences ß diversity of the gut microbiome. Whole blood resuscitation may also mitigate the effects of hemorrhage on intestinal dysbiosis, thereby influencing outcomes.

Impact of the COVID-19 pandemic on trauma activations at a pediatric level 1 trauma center in New York.

BACKGROUND: The disruptive effects on society and medical systems due to the coronavirus disease 2019 (COVID-19) pandemic are substantial and far-reaching. The effect of the pandemic on the quantity and quality of pediatric traumas is unclear and has a direct bearing on how scarce hospital resources should be allocated in a pandemic situation. METHODS: A retrospective review of the trauma registry was performed for trauma activations in the years 2018 through 2020 during the months of March, April, and May. Demographic and injury specific datapoints were compared across calendar years. RESULTS: There were 111, 100, and 52 trauma activations during the study interval in 2018, 2019, and 2020, respectively. There were fewer highest severity level activations in 2020 compared to 2018 and 2019 (1 vs 5 and 9; p < 0.01). The median Injury Severity Score was 5 in 2020 compared to 4 in both 2018 and 2019 (p < 0.01). More patients went directly to the operating room in 2020 compared to prior years (21.2% vs 8% and 6.1%; p < 0.01). There were fewer discharges from the emergency department (ED) (12.1% vs 36.6% and 32.7%). No increase in the number of child abuse reports and investigations was noted. There was no difference in the proportion of blunt versus penetrating trauma between years (p = 0.57). No pedestrians were struck by automobiles in 2020 compared to 12 and 14 in 2018 and 2019. However, there were a greater proportion of injuries from falls during 2020 compared to prior years. CONCLUSIONS: There were fewer trauma activations during the peak of the COVID pandemic compared to prior years. Due to the decrease in trauma volume during the peak of the pandemic, hospital resources could potentially be reallocated toward areas of greater need. LEVEL OF EVIDENCE: IV; Retrospective cohort study using historical controls.

Accuracy of pre-hospital triage tools for major trauma: a systematic review with meta-analysis and net clinical benefit.

BACKGROUND: We conducted a systematic review to evaluate and compare the accuracy of pre-hospital triage tools for major trauma in the context of the development of the Italian National Institute of Health guidelines on major trauma integrated management. METHODS: PubMed, Embase, and CENTRAL were searched up to November 2019 for studies investigating pre-hospital triage tools. The ROC (receiver operating characteristics) curve and net clinical benefit for all selected triage tools were performed. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies-2. Certainty of the evidence was judged with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: We found 15 observational studies of 13 triage tools for adults and 11 for children. In adults, according to the ROC curve and the net clinical benefit, the most reliable tool was the Northern French Alps Trauma System (TRENAU), adopting injury severity score (ISS) > 15 as reference (sensitivity (Sn), 0.92; specificity (Sp), 0.41; 1 study; sample size, 2572; high certainty of the evidence). When mortality as reference was considered, the pre-hospital triage tool with the best net clinical benefit trajectory was the New Trauma Score (NTS) < 18 (Sn, 0.82; Sp, 0.86; 1 study; sample size, 1001; moderate certainty of the evidence). In children, high variability among all triage tools for sensitivity and specificity was found. CONCLUSION: Sensitivity and specificity varied across all available pre-hospital trauma triage tools. TRENAU and NTS are the best accurate triage tools for adults, whereas in the pediatric area a large variability prevents any firm conclusion.

Interobserver variability of injury severity assessment in polytrauma patients: does the anatomical region play a role?

BACKGROUND: The Abbreviated Injury Scale (AIS) and Injury Severity Score (ISS) are widely used to assess trauma patients. In this study, the interobserver variability of the injury severity assessment for severely injured patients was analyzed based on different injured anatomical regions, and the various demographic backgrounds of the observers. METHODS: A standardized questionnaire was presented to surgical experts and participants of clinical polytrauma courses. It contained medical information and initial X-rays/CT-scans of 10 cases of severely injured patients. Participants estimated the severity of each injury based on the AIS. Interobserver variability for the AIS, ISS, and New Injury Severity Score (NISS) was calculated by employing the statistical method of Krippendorff's α coefficient. RESULTS: Overall, 54 participants were included. The major contributing medical specialties were orthopedic trauma surgery (N = 36, 67%) and general surgery (N = 13, 24%). The measured interobserver variability in the assessment of the overall injury severity was high (α ISS: 0.33 / α NISS: 0.23). Moreover, there were differences in the interobserver variability of the maximum AIS (MAIS) depending on the anatomical region: αhead and neck: 0.06, αthorax: 0.45, αabdomen: 0.27 and αextremities: 0.55. CONCLUSIONS: Interobserver agreement concerning injury severity assessment appears to be low among clinicians. We also noted marked differences in variability according to injury anatomy. The study shows that the assessment of injury severity is also highly variable between experts in the field. This implies the need for appropriate education to improve the accuracy of trauma evaluation in the respective trauma registries.

The ICON Trauma Study: the impact of the COVID-19 lockdown on major trauma workload in the UK.

BACKGROUND: The global pandemic caused by SARS-CoV-2 has impacted population health and care delivery worldwide. As information emerges regarding the impact of "lockdown measures" and changes to clinical practice worldwide; there is no comparative information emerging from the United Kingdom with regard to major trauma. METHODS: This observational study from a UK Major Trauma Centre matched a cohort of patients admitted during a 10-week period of the SARS-CoV-2-pandemic (09/03/2020-18/05/2020) to a historical cohort of patients admitted during a similar time period in 2019 (11/03/2019-20/05/2019). Differences in demographics, Clinical Frailty Scale, SARS-CoV-2 status, mechanism of injury and injury severity were compared using Fisher's exact and Chi-squared tests. Univariable and multivariable logistic regression analyses examined the associated factors that predicted 30-days mortality. RESULTS: A total of 642 patients were included, with 405 in the 2019 and 237 in the 2020 cohorts, respectively. 4/237(1.69%) of patients in the 2020 cohort tested positive for SARS-CoV-2. There was a 41.5% decrease in the number of trauma admissions in 2020. This cohort was older (median 46 vs 40 years), had more comorbidities and were frail (p < 0.0015). There was a significant difference in mechanism of injury with a decrease in vehicle related trauma, but an increase in falls. There was a twofold increased risk of mortality in the 2020 cohort which in adjusted multivariable models, was explained by injury severity and frailty. A positive SARS-CoV-2 status was not significantly associated with increased mortality when adjusted for other variables. CONCLUSION: Patients admitted during the COVID-19 pandemic were older, frailer, more co-morbid and had an associated increased risk of mortality.

Comparison of massive and emergency transfusion prediction scoring systems after trauma with a new Bleeding Risk Index score applied in-flight.

BACKGROUND: Assessment of blood consumption (ABC), shock index (SI), and Revised Trauma Score (RTS) are used to estimate the need for blood transfusion and triage. We compared Bleeding Risk Index (BRI) score calculated with trauma patient noninvasive vital signs and hypothesized that prehospital BRI has better performance compared with ABC, RTS, and SI for predicting the need for emergent and massive transfusion (MT). METHODS: We analyzed 2-year in-flight data from adult trauma patients transported directly to a Level I trauma center via helicopter. The BRI scores 0 to 1 were derived from continuous features of photoplethymographic and electrocardiographic waveforms, oximetry values, blood pressure trends. The ABC, RTS, and SI were calculated using admission data. The area under the receiver operating characteristic curve (AUROC) with 95% confidence interval (CI) was calculated for predictions of critical administration threshold (CAT, ≥3 units of blood in the first hour) or MT (≥10 units of blood in the first 24 hours). DeLong's method was used to compare AUROCs for different scoring systems. p < 0.05 was considered statistically significant. RESULTS: Among 1,396 patients, age was 46.5 ± 20.1 years (SD), 67.1% were male. The MT rate was 3.2% and CAT was 7.6%, most (92.8%) were blunt injury. Mortality was 6.6%. Scene arrival to hospital time was 35.3 ± (10.5) minutes. The BRI prediction of MT with AUROC 0.92 (95% CI, 0.89-0.95) was significantly better than ABC, SI, or RTS (AUROCs = 0.80, 0.83, 0.78, respectively; 95% CIs 0.73-0.87, 0.76-0.90, 0.71-0.85, respectively). The BRI prediction of CAT had an AUROC of 0.91 (95% CI, 0.86-0.94), which was significantly better than ABC (AUROC, 077; 95% CI, 0.73-0.82) or RTS (AUROC, 0.79; 95% CI, 0.74-0.83) and better than SI (AUROC, 0.85; 95% CI, 0.80-0.89). The BRI score threshold for optimal prediction of CAT was 0.25 and for MT was 0.28. CONCLUSION: The autonomous continuous noninvasive patient vital signs-based BRI score performs better than ABC, RTS, and SI predictions of MT and CAT. Bleeding Risk Index does not require additional data entry or expert interpretation. LEVEL OF EVIDENCE: Prognostic test, level III.

Increasing BMI is associated with higher mortality, worsening outcomes and highly specific injury patterns following trauma: A multi-institutional analysis of 191,274 patients.

BACKGROUND: As the prevalence of obesity has increased, trauma centers are faced with managing this expanding demographics' unique care requirements. Research on the effects of body mass index (BMI) in trauma patients remains conflicting. This study aims to evaluate the impact of BMI on patterns of injury and patient outcomes following trauma. METHODS: Patients from 87 hospitals' trauma registries were selected. Those missing height, weight, disposition, or who died in the emergency department were excluded. The BMI categories were calculated from admission height and weight and verified against the electronic medical records. Patients were grouped by the National Institutes of Health-defined obesity class and compared by rate of mortality and in-hospital complications. Logistic regression was used to estimate associations, adjusting for age, gender, race, Injury Severity Score, and number of comorbidities. RESULTS: There were 191,274 patients, 53% male; mean age was 60.4 years, mean Glasgow Coma Scale score 14.4, mean Injury Severity Score of 8.8, and 40.4% normal weight. Increased BMI was associated with an injury pattern of increased rates of extremity fractures (humerus, femur, tibia/fibula) and decreased rates of hip fractures and head injuries. Compared with the normal weight group, patients were more likely to die if they were Underweight (adjusted odds ratio [AOR], 1.18; 95% confidence interval [CI], 1.01-1.38), obese class II (AOR, 1.24; 95% CI, 1.07-1.45), or obese class III (AOR, 1.55; 95% CI, 1.29-1.87). Obese class III was associated with higher odds of a National Trauma Data Standard complication (AOR, 1.20; 95% CI, 1.11-1.30). CONCLUSION: In this large multicenter study, increasing BMI and lower than normal BMI were strongly associated with higher mortality. Increasing BMI was also associated with longer length of stay, increased complications, and unique injury patterns. These untoward outcomes, coupled with a distinct injury pattern, warrant care guidelines specific to trauma patients with higher BMI, as well as those with BMI lower than normal. LEVEL OF EVIDENCE: Epidemiological, Level III.

A road map from single-cell transcriptome to patient classification for the immune response to trauma.

Immune dysfunction is an important factor driving mortality and adverse outcomes after trauma but remains poorly understood, especially at the cellular level. To deconvolute the trauma-induced immune response, we applied single-cell RNA sequencing to circulating and bone marrow mononuclear cells in injured mice and circulating mononuclear cells in trauma patients. In mice, the greatest changes in gene expression were seen in monocytes across both compartments. After systemic injury, the gene expression pattern of monocytes markedly deviated from steady state with corresponding changes in critical transcription factors, which can be traced back to myeloid progenitors. These changes were largely recapitulated in the human single-cell analysis. We generalized the major changes in human CD14+ monocytes into 6 signatures, which further defined 2 trauma patient subtypes (SG1 vs. SG2) identified in the whole-blood leukocyte transcriptome in the initial 12 hours after injury. Compared with SG2, SG1 patients exhibited delayed recovery, more severe organ dysfunction, and a higher incidence of infection and noninfectious complications. The 2 patient subtypes were also recapitulated in burn and sepsis patients, revealing a shared pattern of immune response across critical illness. Our data will be broadly useful to further explore the immune response to inflammatory diseases and critical illness.

The swine as a vehicle for research in trauma-induced coagulopathy: Introducing principal component analysis for viscoelastic coagulation tests.

BACKGROUND: Uncontrolled bleeding is the leading cause of potentially preventable deaths among trauma patients. Tissue injury and shock result in trauma-induced coagulopathy (TIC). There are still uncertainties regarding detection methods and best practice management for TIC, and a deeper understanding of the pathophysiology requires robust animal models. The applicability of swine in coagulation studies, particularly after trauma has not been sufficiently elucidated. We, therefore, evaluated the swine as a vehicle for TIC research in a selection of trauma modalities. METHODS: Twenty-six landrace swine (3 females/23 males) (mean weight, 60.0 kg) were anesthetized and randomized to negative controls, receiving no manipulation (n = 5), positive controls by hemodilution (n = 5), pulmonary contusion without hemorrhage (n = 5), pulmonary contusion with hemorrhage (n = 5), and blast polytrauma with hypothermia, hypoperfusion, hypoventilation, and systemic inflammation (n = 6). A comprehensive coagulation panel was analyzed at baseline, 20 minutes and 120 minutes after trauma. RESULTS: PT(INR), aPTT, thrombocytes, and fibrinogen did not change after trauma. D-dimer increased (p < 0.0001), prothrombin decreased (p < 0.05) and aPC decreased (p < 0.01) after polytrauma. PAI-1 decreased after pulmonary contusion with hemorrhage (p < 0.05). Positive controls displayed changes in PT(INR), thrombocytes, fibrinogen, prothrombin, aPC (p < 0.05). Principal Component Analysis of rotational thromboelastometry presented pathologic coagulation profiles in both polytrauma and positive control groups with vectors extending outside the 95% confidence interval, which were not detected in negative controls. CONCLUSION: Coagulopathy was induced after severe porcine blast polytrauma, specifically detected in rotational thromboelastometry. A novel method for principal component analysis of viscoelastic tests was introduced which may increase the detection sensitivity and differentiation of TIC phenotypes and should be further investigated in trauma populations.

Risk Factors of Fat Embolism Syndrome After Trauma: A Nested Case-Control Study With the Use of a Nationwide Trauma Registry in Japan.

BACKGROUND: Fat embolism syndrome (FES) is a rare syndrome resulting from a fat embolism, which is defined by the presence of fat globules in the pulmonary microcirculation; it is associated with a wide range of symptoms. RESEARCH QUESTION: What are the specific unknown risk factors for FES after we have controlled for basic characteristics and patient's severity? STUDY DESIGN AND METHODS: This was a nested case-control study that used the Japan Trauma Data Bank database from 2004 and 2017. We included patients with FES and identified patients without FES as control subjects using a propensity score matching. The primary outcome was the presence of FES during a hospital stay. RESULTS: There were 209 (0.1%) patients with FES after trauma; they were compared with 2,090 matched patients from 168,835 candidates for this study. Patients with FES had long bone and open fractures in their extremities more frequently than those without FES. Regarding treatments, patients with FES received bone reduction and fixation more than those without FES. Among patients who received bone reduction and fixation, time to operation was not different between the groups (P = .63). The overall in-hospital mortality rate was 5.8% in patients with FES and 3.4% in those without FES (P = .11). Conditional logistic regression models to identify risk factors associated with FES shows long bone and open fractures in extremities injury were associated with FES. Primary bone reduction and fixation was not associated independently with FES (OR, 1.80; 95% CI, 0.92-3.54), but delay time to the operation was associated with FES (OR, 2.21; 95% CI, 1.16-4.23). INTERPRETATION: Long bone and open fractures in injuries to the extremities were associated with FES. Although bone reduction and fixation were not associated with FES, delay time to the operation was associated with FES.