Management of complex pediatric and adolescent liver trauma: adult vs pediatric level 1 trauma centers.

PURPOSE: Management of high-grade pediatric and adolescent liver trauma can be complex. Studies suggest that variation exists at adult (ATC) vs pediatric trauma centers (PTC); however, there is limited granular comparative data. We sought to describe and compare the management and outcomes of complex pediatric and adolescent liver trauma between a level 1 ATC and two PTCs in a large metropolitan city. METHODS: A retrospective review of pediatric and adolescent (age < 21 years) patients with American Association for the Surgery of Trauma (AAST) Grade 4 and 5 liver injuries managed at an ATC and PTCs between 2016 and 2022 was performed. Demographic, clinical, and outcome data were obtained at the ATC and PTCs. Primary outcomes included rates of operative management and use of interventional radiology (IR). Secondary outcomes included packed red blood cell (pRBC) utilization, intensive care unit (ICU) length of stay (LOS), and hospital LOS. RESULTS: One hundred forty-four patients were identified, seventy-five at the ATC and sixty-nine at the PTC. The cohort was predominantly black (65.5%) males (63.5%). Six injuries (8.7%) at the PTC and forty-five (60%) injuries at the ATC were penetrating trauma. Comparing only blunt trauma, ATC patients had higher Injury Severity Score (median 37 vs 26) and ages (20 years vs 9 years). ATC patients were more likely to undergo operative management (26.7% vs 11.0%, p = 0.016) and utilized IR more (51.9% vs 4.8%, p < 0.001) compared to the PTC. The patients managed at the ATC required higher rates of pRBC transfusions though not statistically significant (p = 0.06). There were no differences in mortality, ICU, or hospital LOS. CONCLUSION: Our retrospective review of high-grade pediatric and adolescent liver trauma demonstrated higher rates of IR and operating room use at the ATC compared to the PTC in the setting of higher Injury Severity Score and age. While the PTC successfully managed > 95% of Grade 4/5 liver injuries non-operatively, prospective data are needed to determine the optimal algorithm for management in the older adolescent population. LEVEL OF EVIDENCE: Level IV.

Longitudinal Associations Between Pain, Risk for Posttraumatic Stress Disorder, Posttraumatic Stress Symptoms, and Pain Characteristics in Children After Unintentional Injury.

OBJECTIVES: Approximately 20% of children demonstrate persistent posttraumatic stress symptoms (PTSS) after unintentional injury, with more severe pain intensity predicting concurrent and later PTSS. Examining additional pain characteristics like pain behaviors, impairment related to pain, and subjective experiences of pain might provide additional insight into the mechanisms that reinforce relationships between risk for posttraumatic stress disorder (PTSD), PTSS, and pain. METHODS: During hospitalization for unintentional injury, the Screening Tool for Predictors of PTSD (STEPP) was administered and the highest pain score was collected. One month later, the Child PTSD Symptom Scale and PROMIS questionnaires assessed PTSS and pain characteristics respectively, including intensity, interference, behaviors, and quality. RESULTS: Correlations between PTSS and PROMIS questionnaires were significant. STEPP predicted future PTSS and all PROMIS questionnaires. The highest pain score predicted future PTSS, as well as pain interference and pain behavior, and did not predict pain intensity and pain quality. When STEPP and highest pain score were combined into a single regression, STEPP and highest pain score predicted future PTSS but only STEPP continued to predict all PROMIS questionnaires. DISCUSSION: PTSD risk significantly predicted PTSS and pain characteristics 1 month later. The highest pain score predicted future PTSS and several pain characteristics but no longer had predictive value for pain-related outcomes when combined with PTSD risk. These results indicate that risk factors for PTSD are stronger predictors than pain-related risk factors in predicting pain outcomes. Addressing PTSD risk, as well as pain intensity during hospitalization, may result in improved outcomes for children with unintentional injury.

α-Synuclein is the major platelet isoform but is dispensable for activation, secretion, and thrombosis.

Platelets play many roles in the vasculature ensuring proper hemostasis and maintaining integrity. These roles are facilitated, in part, by cargo molecules released from platelet granules via Soluble NSF Attachment Protein Receptor (SNARE) mediated membrane fusion, which is controlled by several protein-protein interactions. Chaperones have been characterized for t-SNAREs (i.e. Munc18b for Syntaxin-11), but none have been clearly identified for v-SNAREs. α-Synuclein has been proposed as a v-SNARE chaperone which may affect SNARE-complex assembly, fusion pore opening, and thus secretion. Despite its abundance and that it is the only isoform present, α-synuclein's role in platelet secretion is uncharacterized. In this study, immunofluorescence showed that α-synuclein was present on punctate structures that co-stained with markers for α-granules and lysosomes and in a cytoplasmic pool. We analyzed the phenotype of α-synuclein-/- mice and their platelets. Platelets from knockout mice had a mild, agonist-dependent secretion defect but aggregation and spreading in vitro were unaffected. Consistently, thrombosis/hemostasis were unaffected in the tail-bleeding, FeCl3 carotid injury and jugular vein puncture models. None of the platelet secretory machinery examined, e.g. the v-SNAREs, were affected by α-synuclein's loss. The results indicate that, despite its abundance, α-synuclein has only a limited role in platelet function and thrombosis.

What did we know? The N-terminus of α-Synuclein affects SNARE-complex assembly, fusion pore opening, and granule docking.Microvascular bleeding is seen in Parkinson Disease patients where α-synuclein has a pathological role.What did we discover? α-Synuclein colocalizes with P-selectin (α-granules) and LAMP-1 (lysosomes) in platelets.The loss of α-synuclein has only a mild, agonist-dependent effect on platelet secretion.The loss of α-synuclein had no effect on thrombosis/hemostasis in 3 injury models.What is the impact? Despite its abundance, α-synuclein is not required for platelet secretion.α-Synuclein is not required for hemostasis or thrombosis.

Standardization of Antibiotic Management and Reduction of Opioid Prescribing in Pediatric Complicated Appendicitis: A Quality Improvement Initiative.

BACKGROUND: Appendicitis is one of the most common pediatric surgical procedures in the United States. However, wide variation remains in antibiotic prescribing and pain management across and within institutions. We aimed to minimize variation in antibiotic usage and decrease opioid prescribing at discharge for children with complicated appendicitis by implementation of a quality improvement (QI) initiative. METHODS: On December 1st, 2021, a QI initiative standardizing postoperative care for complicated appendicitis was implemented across a tertiary pediatric healthcare system with two main surgical centers. QI initiative focused on antibiotic and pain management. An extensive literature search was performed and a total of 20 articles matching our patient population were critically appraised to determine the best evidence-based interventions to implement. Antibiotic regimen included: IV or PO ceftriaxone/metronidazole immediately post-operatively and transition to PO amoxicillin-clavulanic acid for completion of 7-day total course at discharge. Discharge pain control regimen included acetaminophen, ibuprofen, as needed gabapentin, and no opioid prescription. Guideline compliance were closely monitored for the first six months following implementation. RESULTS: In the first 6-months post-implementation, compliance with use of ceftriaxone/metronidazole as initial post-operative antibiotics was 75.6 %. Transition to PO amoxicillin-clavulanic acid prior to discharge increased from 13.7 % pre-implementation to 73.7 % 6-months post-implementation (p < 0.001). Compliance with a 7-day course of antibiotics within the first 6-months post-implementation was 60 % across both sites. After QI intervention, overall opioid prescribing remained at 0 % at one surgical site and decreased from 17.6 % to 0 % at the second surgical site over the study timeframe (p < 0.001). CONCLUSION: Antibiotic use can be standardized and opioid prescribing minimized in children with complicated appendicitis using QI principles. Continued monitoring of the complicated appendicitis guideline is needed to assess for further progress in the standardization of post-operative care. STUDY TYPE: Quality improvement. LEVEL OF EVIDENCE: Level III.

Characterization of spatial lipidomic signatures in tick-bitten guinea pig skin as a model for host-vector-pathogen interaction profiling.

IMPORTANCE: Here, we demonstrate the adaptability of spatial "omics" methods to identify interphylum processes regulated at the vector-host interface of ticks during a mammalian blood meal. This approach enables a better understanding of complex bipartite or tripartite molecular interactions between hosts, arthropod vectors and transmitted pathogens, and contributes toward the development of spatially aware therapeutic target discovery and description.

Pain interference, pain type, and quality of life among adults with spina bifida.

INTRODUCTION: Individuals with spina bifida (SB) experience nociceptive and neuropathic pain, and women with SB report more pain. However, the relationship between pain type and gender on pain interference and quality of life (QoL) among individuals with SB is less understood. OBJECTIVE: To assess relationships among pain interference, pain quality, participation-related QoL, and gender among adults with SB. DESIGN: Fifty-one adults with SB completed a self-report survey assessing SB characteristics, pain severity, pain type, pain interference, and QoL. SETTING: Hospital outpatient adult SB clinic. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Measures of nociceptive pain quality, neuropathic pain quality, participation-related QoL, as well as pain interference with general activities, mood, and sleep were selected a priori as study measures. RESULTS: Fifty-eight percent (N = 30) reported pain and more women than men reported pain (69% vs. 38%, p = .003). Higher general pain interference was associated with lower QoL (r = 0.444, p = .042), but not mood or sleep pain interference (both p's ≥ .451). There was no statistically significant difference in pain interference between genders (p = .138). Nociceptive pain was more common. Levels of nociceptive pain were positively associated with general pain interference, sleep pain interference, and mood pain inference. Neither pain type was associated with QoL (both p's > .082). CONCLUSIONS: The results from this study reveal key differences/similarities among four interrelated factors: pain, pain interference, QoL, and gender. Pertinent information gathered on pain type and QoL, like increased prevalence of nociceptive pain, can be utilized to formulate proactive and effective treatment plans for individuals with SB that may benefit their sleep pain interference and mood pain interference.

The complementary roles of VAMP-2, -3, and -7 in platelet secretion and function.

Platelet secretion requires Soluble N-ethylmaleimide Sensitive Attachment Protein Receptors (SNAREs). Vesicle SNAREs/Vesicle-Associated Membrane Proteins (v-SNAREs/VAMPs) on granules and t-SNAREs in plasma membranes mediate granule release. Platelet VAMP heterogeneity has complicated the assessment of how/if each is used and affects hemostasis. To address the importance of VAMP-7 (V7), we analyzed mice with global deletions of V3 and V7 together or platelet-specific deletions of V2, V3, and global deletion of V7. We measured the kinetics of cargo release, and its effects on three injury models to define the context-specific roles of these VAMPs. Loss of V7 minimally affected dense and α granule release but did affect lysosomal release. V3-/-7-/- and V2Δ3Δ7-/- platelets showed partial defects in α and lysosomal release; dense granule secretion was unaffected. In vivo assays showed that loss of V2, V3, and V7 caused no bleeding or occlusive thrombosis. These data indicate a role for V7 in lysosome release that is partially compensated by V3. V7 and V3, together, contribute to α granule release, however none of these deletions affected hemostasis/thrombosis. Our results confirm the dominance of V8. When it is present, deletion of V2, V3, or V7 alone or in combination minimally affects platelet secretion and hemostasis.

What did we know? V8 is the primary VAMP isoform for platelet granule secretion, but V2 and V3 play compensatory roles.V3 is important for platelet endocytosis.V7 plays a minimal role in secretion and does not affect hemostasis.What did we discover? The loss of both V3 and V7 increases α and lysosomal secretion defects.Platelet-specific deletion of V2 and V3 with global V7-deletion causes defective α and lysosomal release.Secretion deficiencies in V3^−/−7^−/− and V2^Δ3^Δ7^−/− have no effect on hemostasis or thrombosis.What is the impact? We show that endosomal v-SNAREs (V3 and V7) play minor roles in secretion.V3^−/−7^−/− and platelet-specific V2^Δ3^Δ7^−/− mice are viable and will be valuable in in vivo studies of membrane trafficking.

Protective antibody threshold of RTS,S/AS01 malaria vaccine correlates antigen and adjuvant dose in mouse model.

Mouse models are useful for the early down-selection of malaria vaccine candidates. The Walter Reed Army Institute of Research has optimized a transgenic Plasmodium berghei sporozoite challenge model to compare the efficacy of Plasmodium falciparum circumsporozoite protein (CSP) vaccines. GSK's RTS,S vaccine formulated in the adjuvant AS01 can protect malaria-naïve individuals against malaria. We report that the RTS,S/AS01 vaccine induces high level sterile protection in our mouse model. Down titration of the antigen at a constant AS01 dose revealed a potent antigen dose-sparing effect and the superiority of RTS,S/AS01 over a soluble CSP antigen. RTS,S-mediated protective immunity was associated with a threshold of major repeat antibody titer. Combined titration of the antigen and adjuvant showed that reducing the adjuvant could improve antibody boosting post-3rd vaccination and reduce the threshold antibody concentration required for protection. Mouse models can provide a pathway for preclinical assessment of strategies to improve CSP vaccines against malaria.

Increases in adolescent firearm injuries were associated with school closures during COVID-19.

BACKGROUND: Mitigation measures, including school closures, were enacted to protect the public during the COVID-19 pandemic. However, the negative effects of mitigation measures are not fully known. Adolescents are uniquely vulnerable to policy changes since many depend on schools for physical, mental, and/or nutritional support.  This study explores the statistical relationships between school closures and adolescent firearm injuries (AFI) during the pandemic. METHODS: Data were drawn from a collaborative registry of 4 trauma centers in Atlanta, GA (2 adult and 2 pediatric). Firearm injuries affecting adolescents aged 11-21 years from 1/1/2016 to 6/30/2021 were evaluated. Local economic and COVID data were obtained from the Bureau of Labor Statistics and the Georgia Department of Health. Linear models of AFI were created based on COVID cases, school closure, unemployment, and wage changes. RESULTS: There were 1,330 AFI at Atlanta trauma centers during the study period, 1,130 of whom resided in the 10 metro counties. A significant spike in injuries was observed during Spring 2020. A season-adjusted time series of AFI was found to be non- stationary (p = 0.60). After adjustment for unemployment, seasonal variation, wage changes, county baseline injury rate, and county-level COVID incidence, each additional day of unplanned school closure in Atlanta was associated with 0.69 (95% CI 0.34- 1.04, p < 0.001) additional AFIs across the city. CONCLUSION: AFI increased during the COVID pandemic. This rise in violence is statistically attributable in part to school closures after adjustment for COVID cases, unemployment, and seasonal variation. These findings reinforce the need to consider the direct implications on public health and adolescent safety when implementing public policy.

Ferric Chloride-Induced Arterial Thrombosis and Sample Collection for 3D Electron Microscopy Analysis.

Cardiovascular diseases are a leading cause of mortality and morbidity worldwide. Aberrant thrombosis is a common feature of systemic conditions like diabetes and obesity, and chronic inflammatory diseases like atherosclerosis, cancer, and autoimmune diseases. Upon vascular injury, usually the coagulation system, platelets, and endothelium act in an orchestrated manner to prevent bleeding by forming a clot at the site of the injury. Abnormalities in this process lead to either excessive bleeding or uncontrolled thrombosis/insufficient antithrombotic activity, which translates into vessel occlusion and its sequelae. The FeCl3-induced carotid injury model is a valuable tool in probing how thrombosis initiates and progresses in vivo. This model involves endothelial damage/denudation and subsequent clot formation at the injured site. It provides a highly sensitive, quantitative assay to monitor vascular damage and clot formation in response to different degrees of vascular damage. Once optimized, this standard technique can be used to study the molecular mechanisms underlying thrombosis, as well as the ultrastructural changes in platelets in a growing thrombus. This assay is also useful to study the efficacy of antithrombotic and antiplatelet agents. This article explains how to initiate and monitor FeCl3-induced arterial thrombosis and how to collect samples for analysis by electron microscopy.

Trends in Adolescent Firearm-Related Injury: A Time Series Analysis.

BACKGROUND: Firearm-related injury (FRI) became the leading cause of death among children/adolescents in 2019. PURPOSE: This study sought to determine changes over time in the population of adolescents affected by FRI in Atlanta, Georgia, such that high risk cohorts could be identified. RESEARCH DESIGN: City-wide retrospective cohort review. STUDY SAMPLE: Adolescent victims (age 11-21 years of age) of FRI, defined by ICD9/10 codes, in Atlanta, Georgia. DATA ANALYSIS: Descriptive, multivariate and time series analysis. RESULTS: There were 1,453 adolescent FRI victims in this time period, predominantly Black (86%) and male (86.6%). Unintentional injury was higher among ages 11-14 years (43.1%) compared to 15-17 years (10.2%) and 18-21 years (9.3%) (P < .01). FRI affecting females increased at a rate of 8.1 injuries/year (P < .01), and unintentional injuries increased at by 7.6/year (P < .01). Mortality declined from 16% in 2016 to 7.7% in 2021. CONCLUSION: Our data provides evidence for firearm policy reform. Interventions should target prevention of intentional injury among AQ4 females and seek to reverse the trend in unintentional injuries.

Dome1-JAK-STAT signaling between parasite and host integrates vector immunity and development.

Ancestral signaling pathways serve critical roles in metazoan development, physiology, and immunity. We report an evolutionary interspecies communication pathway involving a central Ixodes scapularis tick receptor termed Dome1, which acquired a mammalian cytokine receptor motif exhibiting high affinity for interferon-gamma (IFN-γ). Host-derived IFN-γ facilitates Dome1-mediated activation of the Ixodes JAK-STAT pathway. This accelerates tick blood meal acquisition and development while upregulating antimicrobial components. The Dome1-JAK-STAT pathway, which exists in most Ixodid tick genomes, regulates the regeneration and proliferation of gut cells-including stem cells-and dictates metamorphosis through the Hedgehog and Notch-Delta networks, ultimately affecting Ixodes vectorial competence. We highlight the evolutionary dependence of I. scapularis on mammalian hosts through cross-species signaling mechanisms that dually influence arthropod immunity and development.

miR-542-5p targets c-myc and negates the cell proliferation effect of SphK1 in intestinal epithelial cells.

Intestinal epithelial barrier defects occur commonly during a variety of pathological conditions, though their underlying mechanisms are not completely understood. Sphingosine-1-phosphate (S1P) has been shown to be a critical regulator of proliferation and of maintenance of an intact intestinal epithelial barrier, as is also sphingosine kinase 1 (SphK1), the rate-limiting enzyme for S1P synthesis. SphK1 has been shown to modulate its effect on intestinal epithelial proliferation through increased levels of c-myc. We conducted genome-wide profile analysis to search for differential microRNA expression related to overexpressed SphK1 demonstrating adjusted expression of microRNA 542-5p (miR-542-5p). Here, we show that miR-542-5p is regulated by SphK1 activity and is an effector of c-myc translation that ultimately serves as a critical regulator of the intestinal epithelial barrier. miR-542-5p directly regulates c-myc translation through direct binding to the c-myc mRNA. Exogenous S1P analogs administered in vivo protect murine intestinal barrier from damage due to mesenteric ischemia reperfusion, and damaged intestinal tissue had increased levels of miR-542-5p. These results indicate that miR-542-5p plays a critical role in the regulation of S1P-mediated intestinal barrier function, and may highlight a novel role in potential therapies.

Function and evolution of the aquaporin IsAQP1 in the Lyme disease vector Ixodes scapularis.

Ticks are important vectors of pathogenic viruses, bacteria, and protozoans to humans, wildlife, and domestic animals. Due to their life cycles, ticks face significant challenges related to water homeostasis. When blood-feeding, they must excrete water and ions, but when off-host (for stretches lasting several months), they must conserve water to avoid desiccation. Aquaporins (AQPs), a family of membrane-bound water channels, are key players in osmoregulation in many animals but remain poorly characterized in ticks. Here, we bioinformatically identified AQP-like genes from the deer tick Ixodes scapularis and used phylogenetic approaches to map the evolution of the aquaporin gene family in arthropods. Most arachnid AQP-like sequences (including those of I. scapularis) formed a monophyletic group clustered within aquaglycerolporins (GLPs) from bacteria to vertebrates. This gene family is absent from insects, revealing divergent evolutionary paths for AQPs in different hematophagous arthropods. Next, we sequenced the full-length cDNA of I. scapularis aquaporin 1 (IsAQP1) and expressed it heterologously in Xenopus oocytes to functionally characterize its permeability to water and solutes. Additionally, we examined IsAQP1 expression across different life stages and adult female organs. We found IsAQP1 is an efficient water channel with high expression in salivary glands prior to feeding, suggesting it plays a role in osmoregulation before or during blood feeding. Its functional properties are unique: unlike most GLPs, IsAQP1 has low glycerol permeability, and unlike most AQPs, it is insensitive to mercury. Together, our results suggest IsAQP1 plays an important role in tick water balance physiology and that it may hold promise as a target of novel vector control efforts.

Angina pain associated with isolated R-IIP modified Lipton classification coronary artery anomaly.

We report a case of a patient that presented with typical angina pain and associated risk factors for coronary artery disease (CAD). Subsequent cardiac catheterisation led to the discovery of an isolated R-IIP modified Lipton classification coronary artery anomaly with follow-up coronary computed tomography angiography (CCTA) confirmation. This case report includes images of the CCTA and left heart catheterisation results, along with a discussion of the potential for increased risk of atherosclerosis in our patient, and a proposed explanation of his presentation with prototypical angina pain, despite lack of apparent atherosclerosis.

Nutrition and behavior change: a review of recent literature.

PURPOSE OF REVIEW: The current article will highlight recent trends and novel approaches to behavior change strategies in nutrition. Physicians, nurses, and other healthcare professionals play key roles in counseling patients on lifestyle change, which is critical for patients with chronic conditions. Nutrition science continues to advance, and new approaches to behavior change are needed for successful implementation at the individual and population level. RECENT FINDINGS: The solutions to obstacles around healthful eating patterns are varied, population-dependent, and require a multipronged approach. One area of focus is the language around behavior change, ensuring it is clear and emphasizes its multifactorial nature. For young adults, the careful use of video games and social media may be essential. For older adults, altering food consistency and ensuring proper nutrient intake are crucial factors. Vulnerable populations remain susceptible to malnutrition and need special attention. Despite significant advances in managing and treating diseases, there are still gaps in nutrition counseling and behavior change efforts. SUMMARY: Every age and stage of life needs a focus on healthful foods, and nutrition counseling at each stage has its unique nuances. Careful attention to the language of change and the phrasing used in counseling is vital for educating, connecting with, and empowering patients to change. Changing healthcare operations and provider behavior around nutrition counseling is a part of the solution to the worldwide problem of unhealthy eating patterns and practices.

PTSD Risk Factors and Acute Pain Intensity Predict Length of Hospital Stay in Youth after Unintentional Injury.

Background: Many hospitals have adopted screening tools to assess risk for posttraumatic stress disorder (PTSD) after pediatric unintentional injury in accordance with American College of Surgeons recommendations. The Screening Tool for Early Predictors of PTSD (STEPP) is a measure initially developed to identify youth and parents at high risk for meeting diagnostic criteria for PTSD after injury. Acute pain during hospitalization has also been examined as a potential predictor of maladaptive outcomes after injury, including PTSD. We investigated in a retrospective cohort study whether the STEPP, as well as acute pain intensity during hospitalization, would predict maladaptive outcomes during the peri-trauma in addition to the post-trauma period, specifically length of hospitalization. Methods: A total of 1123 youths aged 8-17 (61% male) and their parents were included. Patients and parents were administered the STEPP for clinical reasons while hospitalized. Acute pain intensity and length of stay were collected through retrospective chart review. Results: Adjusting for demographics and injury severity, child but not parent STEPP total predicted length of stay. Acute pain intensity, child threat to life appraisal, and child pulse rate predicted length of stay. Conclusions: Acute pain intensity and child PTSD risk factors, most notably child threat to life appraisal, predicted hospitalization length above and beyond multiple factors, including injury severity. Pain intensity and child appraisals may not only serve as early warning signs for maladaptive outcomes after injury but also indicate a more difficult trajectory during hospitalization. Additional assessment and treatment of these factors may be critical while youth are hospitalized. Utilizing psychology services to support youth and integrating trauma-informed care practices during hospitalization may support improved outcomes for youth experiencing unintentional injury.