Hypofibrinogenemia following injury in 186 children and adolescents: identification of the phenotype, current outcomes, and potential for intervention.

Objectives: Recent studies evaluating fibrinogen replacement in trauma, along with newly available fibrinogen-based products, has led to an increase in debate on where products such as cryoprecipitate belong in our resuscitation strategies. We set out to define the phenotype and outcomes of those with hypofibrinogenemia and evaluate whether fibrinogen replacement should have a role in the initial administration of massive transfusion. Methods: All patients <18 years of age presenting to our trauma center 11/17-4/21 were reviewed. We then evaluated all patients who received emergency-release and massive transfusion protocol (MTP) products. Patients were defined as hypofibrinogenemic (HYPOFIB) if admission fibrinogen <150 or rapid thrombelastography (r-TEG) angle <60 degrees. Our analysis sought to define risk factors for presenting with HYPOFIB, the impact on outcomes, and whether early replacement improved mortality. Results: 4169 patients were entered into the trauma registry, with 926 level 1 trauma activations, of which 186 patients received emergency-release blood products during this time; 1%, 3%, and 10% were HYPOFIB, respectively. Of the 186 patients of interest, 18 were HYPOFIB and 168 were non-HYPOFIB. The HYPOFIB patients were significantly younger, had lower field and arrival Glasgow Coma Scale, had higher head Abbreviated Injury Scale, arrived with worse global coagulopathy, and died from brain injury. Non-HYPOFIB patients were more likely to have (+)focused assessment for the sonography of trauma on arrival, sustained severe abdominal injuries, and die from hemorrhage. 12% of patients who received early cryoprecipitate (0-2 hours) had higher mortality by univariate analysis (55% vs 31%, p=0.045), but no difference on multivariate analysis (OR 0.36, 95% CI 0.07 to 1.81, p=0.221). Those receiving early cryoprecipitate who survived after pediatric intensive care unit (PICU) admission had lower PICU fibrinogen and r-TEG alpha-angle values. Conclusion: In pediatric trauma, patients with hypofibrinogenemia on admission are most likely younger and to have sustained severe brain injury, with an associated mortality of over 80%. Given the absence of bleeding-related deaths in HYPOFIB patients, this study does not provide evidence for the empiric use of cryoprecipitate in the initial administration of a massive transfusion protocol. Level of Evidence: Level III - Therapeutic/Care Management.

An assessment of the safety, hemostatic efficacy, and clinical impact of low-titer group O whole blood in children and adolescents.

BACKGROUND: Low-titer group O whole blood (LTOWB) use has been associated with improved survival and less blood transfusions in adult trauma patients. Its use in pediatric trauma has been shown to be safe when using leukoreduced, LTOWB with anti-A, anti-B antibody titers of <1:50. We set out to evaluate the safety, hemostatic potential, and impact on pediatric outcomes at a center using non-leukoreduced, LTOWB with anti-A, anti-B antibody titers of <1:200. METHODS: Patients younger than 18 years, who received emergency-release, uncrossed matched blood, and presented to our trauma center from November 2017 to April 2021 were included. Patients were divided into those receiving any LTOWB and those receiving only RBC and or plasma (COMP). Primary outcome was 30-day survival. RESULTS: One hundred sixty-four patients received emergency release blood products. Of these, 73 received at least one unit of LTOWB. The LTOWB group were younger (14 years vs. 13 years), more likely to be male (87% vs. 49%), and to have sustained penetrating trauma (44% vs. 23%); all p < 0.05. Low-titer group O whole blood patients received more blood than their COMP counterparts prior to arrival. Serial hemolysis panels (K+, bilirubin, LDH, haptoglobin) obtained at 24 hours, 48 hours, and 72 hours were similar between groups; all p > 0.05. There was no difference in survival by univariate analysis but after adjusting for inverse probability of treatment weights there was an observed association between WB administration and improved survival, with an odds ratio of 2.48 (1.15-5.47). CONCLUSION: Non-leukoreduced, LTOWB in anti-A/anti-B antibody titers of <1:200 appear safe in children and adolescents. While patients receiving LTOWB had more evidence of shock, higher torso injury severity, and received more prehospital blood products, there may be a mortality benefit with whole blood. Larger, multicenter studies are needed. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Do All Abdominal Neuroendocrine Tumors Require Extended Postoperative VTE Prophylaxis? A NSQIP Analysis.

BACKGROUND: Venous thromboembolism (VTE) occurs at high incidence in abdominal cancer surgery; therefore, a 4-week postoperative VTE prophylaxis is advocated. However, most patients with neuroendocrine tumors (NETs) have more favorable prognoses. This study aimed to determine the incidence of VTE in patients with abdominal NETs, compare these rates to other abdominal malignancies, and identify VTE risk factors. METHODS: The ACS-NSQIP database was queried to identify patients with abdominal NETs and other abdominal malignancies who underwent surgery from 2008 to 2015. A 30-day postoperative VTE incidence for each group was compared. Univariable and multivariable analyses were used to identify VTE risk factors. RESULTS: Of the 7226 operations for patients with benign (2154) and malignant (5072) abdominal NETs, 144 patients experienced a VTE without significant differences between groups. Subgroup analysis revealed a spectrum of VTE rates. Compared to VTE rates of other abdominal malignancies, patients with benign (1.1% vs. 2.4%, p < 0.001) or malignant (1.7% vs. 2.4%, p < 0.001) non-pancreatic abdominal NETs had significantly lower rates, malignant pancreatic NETs (PNETs) (3.4% vs. 2.4%, p = 0.03) had significantly higher rates, and benign PNETs (3.2% vs. 2.4%, p = 0.21) had comparable rates. Multivariable analysis identified pre-operative albumin (p < 0.001), bleeding disorders (p < 0.001), operative time (p < 0.001), and having a PNET (p = 0.04) as risk factors for VTE in abdominal NET patients. CONCLUSION: Routine extended VTE prophylaxis after surgery may be necessary in PNETs, but probably unnecessary in other abdominal NETs. However, clinicians should use risk factors identified in this study when considering to forego extended VTE prophylaxis in NET patients.

Acute cholecystitis: comparing clinical outcomes with TG13 severity and intended laparoscopic versus open cholecystectomy in difficult operative cases.

INTRODUCTION: The revised Tokyo Guidelines include criteria for determining the severity of acute cholecystitis with treatment algorithms based on severity. The aim of this study was to investigate the relationship of the revised Tokyo Guidelines severity grade to clinical outcomes of cholecystectomy for acute cholecystitis. METHODS: We identified 66 patients with acute cholecystitis from a prior study of difficult cholecystectomy cases. We examined the relationship between severity grade and multiple variables related to perioperative and postoperative outcomes. RESULTS: A more severe revised Tokyo Guidelines grade was associated with a higher number of complications (p = 0.03) and a higher severity of complications (p = 0.01). Severity grade did not predict operative time, estimated blood loss, intensive care unit admission or length of stay. Compared to planned open cholecystectomy, intended laparoscopic cholecystectomy was associated with significantly fewer total and Clavien-Dindo grade 3 complications, fewer intensive care unit admissions, and shorter length of stay (p values range from 0.03 to < 0.0001). CONCLUSION: In technically difficult operations for acute cholecystitis, the revised Tokyo guidelines severity grade correlates with the number and severity of complications. However, intended performance of laparoscopic cholecystectomy rather than open cholecystectomy in difficult operations predicts broader beneficial outcomes than severity grade.

Severe, multimodal stress exposure induces PTSD-like characteristics in a mouse model of single prolonged stress.

Appropriate animal models of posttraumatic stress disorder (PTSD) are needed because human studies remain limited in their ability to probe the underlying neurobiology of PTSD. Although the single prolonged stress (SPS) model is an established rat model of PTSD, the development of a similarly-validated mouse model emphasizes the benefits and cross-species utility of rodent PTSD models and offers unique methodological advantages to that of the rat. Therefore, the aims of this study were to develop and describe a SPS model for mice and to provide data that support current mechanisms relevant to PTSD. The mouse single prolonged stress (mSPS) paradigm, involves exposing C57Bl/6 mice to a series of severe, multimodal stressors, including 2h restraint, 10 min group forced swim, exposure to soiled rat bedding scent, and exposure to ether until unconsciousness. Following a 7-day undisturbed period, mice were tested for cue-induced fear behavior, effects of paroxetine on cue-induced fear behavior, extinction retention of a previously extinguished fear memory, dexamethasone suppression of corticosterone (CORT) response, dorsal hippocampal glucocorticoid receptor protein and mRNA expression, and prefrontal cortex glutamate levels. Exposure to mSPS enhanced cue-induced fear, which was attenuated by oral paroxetine treatment. mSPS also disrupted extinction retention, enhanced suppression of stress-induced CORT response, increased mRNA expression of dorsal hippocampal glucocorticoid receptors and decreased prefrontal cortex glutamate levels. These data suggest that the mSPS model is a translationally-relevant model for future PTSD research with strong face, construct, and predictive validity. In summary, mSPS models characteristics relevant to PTSD and this severe, multimodal stress modifies fear learning in mice that coincides with changes in the hypothalamo-pituitary-adrenal (HPA) axis, brain glucocorticoid systems, and glutamatergic signaling in the prefrontal cortex.