Publications

BACKGROUND: Traumatic Brain Injury (TBI) is the leading cause of traumatic pediatric mortality. This study examined the safety of early plasma administration in children with severe TBI.

METHODS: A retrospective cohort study using data from a Level 1 pediatric trauma center from 2016-2023 was conducted. Children <18 years old with severe TBI (head Abbreviated Injury Scale (AIS) >2 and requiring ICU admission) who received component plasma within 24 hours of injury were included. Isolated asphyxiation and neck trauma were excluded. Subjects who received "early" plasma (≤4 hours from injury) were propensity matched for age, sex, admission GCS, shock, ISS, maximum head AIS, and injury mechanism with those who received "delayed" plasma (>4-24 hours post-injury). Adjusted logistic regression on the matched cohort assessed the association between plasma timing and 28-day mortality.

RESULTS: Overall, 71 children met inclusion criteria; 31 received early and 40 received delayed plasma. The cohort was mostly male (66.2%) and injured via blunt mechanism (83.1%), with median(IQR) age 4 years (1-11) years, ISS 30(26-38), head AIS 5(4-5), and 28-day mortality rate of 62.0%. Among 31 propensity-matched pairs, there was no significant association between plasma timing and adjusted odds of 28-day mortality (Odds Ratio of early plasma 1.75 (95% CI: 0.42-7.31), p=0.443), no transfusion reaction, and no increase in adverse events.

CONCLUSIONS: In this study of children with severe TBI, there were no apparent safety concerns with the receipt of early plasma compared to delayed plasma. Overall mortality was high, demonstrating need for additional therapies for this vulnerable population.

TYPE OF STUDY: Retrospective cohort study LEVEL OF EVIDENCE: Level III.

INTRODUCTION: Tourniquet (TQ) use is conditionally recommended in injured children largely on the basis of adult data. This investigation seeks to better understand tourniquet use and safety in a pediatric cohort.

METHODS: A pediatric level 1 trauma center database was queried retrospectively for patients aged 0-17 years who presented with traumatic limb injury and TQ application between 2015-2022. Data recorded included demographics, injury characteristics, TQ use variables (number, location, person applying, proper application) and adverse events (kidney injury, amputation, rhabdomyolysis, nerve injury, compartment syndrome). Data were summarized using counts, median, and percentages.

RESULTS: In total, 37 children who had a total of 51 TQs applied were included. Their median (IQR) age was 14 years (10-15), 27/37 and (72%) were male. The median (IQR) injury severity score was 9 (5-10), mechanism of injury was 70% penetrating, and 19% (7/37) were in shock on arrival. Of the 37 children, 27 (73%) required an urgent operation. The in-hospital mortality rate was 0%, and 36/37 (97%) were discharged home. In total, 11/51(22%) TQs were applied by bystanders, 21/51 (41%) by Fire/EMS, 14/51 (32%) by police, and 4/51 (8%) by hospital clinical staff. Overall, 30/37 (81%) had properly applied TQs. No patient had an adverse complication related to TQ application.

CONCLUSION: In this cohort of injured children, tourniquet use was feasible and safe. Larger studies are needed to generate pediatric-specific evidence-based guidelines for TQ use; widespread clinician training may increase the rate of proper application.

LEVEL OF EVIDENCE: Level 3, Cohort Study.

OBJECTIVES: To characterize the epidemiology and management of massive bleeding events in children with cancer and/or hematopoietic cell transplant (HCT).

DESIGN: Multicenter, retrospective cohort study.

SETTING: Nineteen pediatric hospitals in Europe and United States.

SUBJECTS: Children ages 0-21 years old with malignancy and/or HCT and massive bleeding admitted from January 1, 2017, to December 31, 2021.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Demographics, oncologic history, laboratory values, interventions, and PICU outcomes were collected. One hundred fifty-two bleeding episodes from 135 patients were analyzed. The median (interquartile range [IQR]) age was 7 years (2-14 yr). Forty-three percent (58/135) were female sex. Nineteen percent of children (26/135) had death attributable to hemorrhage. Forty percent had solid tumors and one-third had undergone at least one HCT. The majority of bleeding events occurred in the PICU (81/152, 53%). The median (IQR) platelet count at time of bleeding was 52 × 10 9 /L (24-115 × 10 9 /L), prothrombin time 18.5 seconds (15.2-24.8 s), activated partial thromboplastin time 42.2 seconds (33.2-56.0 s), and international normalized ratio 1.51 (1.21-2.11). To treat these bleeding events, 99% (148/152) of the time children received RBC transfusions, 84% (126/152) of the time plasma transfusions, 88% (132/152) of the time platelet transfusions, and less than one-fifth hemostatic medications. Half (77/152, 52%) of the time the children received high plasma ratios and half (73/152, 49%) received high platelet ratios. Pulmonary bleeding, oral/nasal bleeding, and receipt of prothrombin complex concentrate were each associated with greater odds of death attributed to hemorrhage: odds ratio (95% CI), respectively: 5.44 (2.250-13.171; p < 0.001); 3.30 (1.20-9.09; p = 0.021); and 3.24 (1.18-8.93; p = 0.023).

CONCLUSIONS: Children with malignancy and/or HCT have a high mortality rate from hemorrhage despite being hospitalized at the time of their bleeding event. The majority of children received balanced resuscitation. Definitive trials are needed to determine optimal hemostatic resuscitation practice in this population.

BACKGROUND: There has been renewed interest in cold-stored platelets (CSPs) for the management of bleeding patients. CSPs might offer advantages over conventional room temperature stored platelet units (RTP), such as a lower risk of bacterial growth during storage, a longer shelf lf life, and possibly improved hemostatic effectiveness. However, CSPs have reduced in vivo survival compared to RTP. In 2023, the FDA issued guidance allowing 14-day storage of CSPs for the treatment of active bleeding when conventional platelets are not available or their use is not practical. This How Do We describes various scenarios of CSP use, followed by the authors' assessment regarding consistency with FDA recommendations.

METHODS: The authors contributed scenarios that reflected their institutions' unique settings or more generalized scenarios common to other centers. The authors offered their interpretation of the guidance for each specific situation.

RESULTS: Seven scenarios are provided that demonstrate potentially appropriate or clearly inappropriate CSP use across a variety of settings. The authors' interpretations aim to help hospital transfusion services develop standard operating procedures (SOPs) that are suitable for their own unique circumstances.

DISCUSSION: Each hospital has a unique setting and set of conditions that influence CSP use. This How Do We provides the authors' assessments regarding how CSPs may be used in certain scenarios; however, this is not a guide and does not offer official recommendations. Every center must develop SOPs that account for usage patterns and inventory constraints specific to its own environment.

INTRODUCTION: Hemorrhage is the major cause of early, preventable trauma deaths. We provide a contemporary(2018-2021) description of deaths of patients at risk for lethal traumatic hemorrhage admitted to seven trauma centers equipped with the most advanced hemostatic therapies.

METHODS: This is a secondary analysis of non-survivors of the multicenter SWAT study, which enrolled patients at high-risk for life-threatening hemorrhage(age>15yrs, required blood ​+ ​surgical/embolization hemorrhage control procedures<1 ​h; penetrating head injury and >5min CPR were excluded. Causes of death(COD) were prospectively adjudicated by the SWAT team of trauma surgeons.

RESULTS: Of 1051 patients, 176(16.7 ​%) died(74 ​% ​< ​24 ​h,56 ​%<6 ​h,35 ​%<3 ​h). Bleeding was the main COD, occurring mostly <3 ​h. Over one third of these patients had a TRISS estimated survival probability>50 ​%. TBI was the COD in 10 ​% of the deaths(TRISS ​= ​8 ​%), mostly 12-48 ​h. The third COD was organ failure, in 9 ​%(TRISS ​= ​25 ​%), often >48 ​h.

CONCLUSION: Uncontrolled bleeding in patients with high probability of survival remains a challenge to reduce preventable trauma deaths.

Vibronic coupling (VC) is especially important in excited state systems and results in the overlap of both electronic and vibrational adiabatic potential energy surfaces. Previously, two-dimensional vibrational-electronic spectroscopy has been developed for VC for studies in bulk systems. Here we demonstrate interface-specific 2D vibrational-electronic spectroscopy (i2D-VE) to directly study interactions of vibrational and electronic motions of azo-dye molecules at the air/water interfaces. After laying the theoretical framework for i2D-VE, we used it to quantify relative orientations of the coupled vibrational and electronic dipoles. We further examined time-dependent i2D-VE spectra for interfacial water coupling with vibrational and electronic transitions. Comparisons with simulated i2D-VE spectra correlated with experimental data to confirm the relationship between the interfacial solvation structure and VC therein. These results open venues to track the orientational coupling, dynamic solvent coupling, and structural evolution of photoinduced excited states at interfaces and surfaces.

PURPOSE OF REVIEW: This review examines the enzymatic regulation of coagulation and fibrinolysis, focusing on key players such as thrombin, plasmin, and ADAMTS13. We highlight how dysregulation of these enzymes contributes to thrombotic and hemorrhagic disorders and review emerging diagnostic biomarkers and therapeutic strategies.

RECENT FINDINGS: Recent studies demonstrate the prognostic utility of biomarkers such as thrombin-antithrombin (TAT) and plasmin-α2-antiplasmin (PAP) complexes across critical illnesses including trauma, sepsis, and stroke. Advances in plasmin and thrombin generation assays, enzyme-specific assays, and enzyme-modulating therapies (e.g., factor XI inhibitors and recombinant ADAMTS13) are reshaping approaches to hemostatic balance.

SUMMARY: Understanding hemostatic enzymatic regulation offers new avenues for risk stratification, diagnosis, and treatment of coagulation disorders. Although significant progress has been made, challenges remain in translating laboratory findings to clinical practice, necessitating further large-scale validation. Precision-guided enzymatic therapies hold promise for improving outcomes in acute care settings.