Strategies to Obtain and Deliver Blood Products Into Critically Injured Children: A Survey of Pediatric Trauma Society Members.

OBJECTIVES: Timely transfusion is associated with improved survival and a reduction in in-hospital morbidity. The benefits of early hemorrhagic shock recognition may be limited by barriers to accessing blood products and their timely administration. We examined how pediatric trauma programs obtain blood products, the types of rapid infusion models used, and the metrics tracked to improve transfusion process efficiency in their emergency department (ED). METHODS: We developed and distributed a self-report survey to members of the Pediatric Trauma Society. The survey consisted of 6 initial questions, including the respondent's role and institution, whether a blood storage refrigerator was present in their ED, the rapid infuser model used to transfuse critically injured children in their ED, if their program tracked 4 transfusion process metrics, and if a video recording system was present in the trauma bay. Based on these responses, additional questions were prompted with an option for a free-text response. RESULTS: We received 137 responses from 77 institutions. Most pediatric trauma programs have a blood storage refrigerator in the ED (n = 46, 59.7%) and use a Belmont rapid infuser to transfuse critically injured children (n = 45, 58.4%). The American College of Surgeons Level 1 designated trauma programs, or state-based equivalents, and "pediatric" trauma programs were more likely to have video recording systems for performance improvement review compared with lower designated trauma programs and "combined pediatric and adult" trauma programs, respectively. CONCLUSIONS: Strategies to improve the timely acquisition and infusion of blood products to critically injured children are underreported. This study examined the current practices that pediatric trauma programs use to transfuse critically injured children and may provide a resource for trauma programs to cite for transfusion-related quality improvement.

Urinary microbiome differences between lichen sclerosus induced and non-lichen sclerosus induced urethral stricture disease.

OBJECTIVE: To describe differences in the urinary microbiome of patients with pathologically confirmed lichen sclerosus (LS) urethral stricture disease (USD) vs non-lichen sclerosus (non-LS) USD pre- and post-operatively. METHODS: Patients were pre-operatively identified and prospectively followed, all underwent surgical repair and had tissue samples obtained to make a pathological diagnosis of LS. Pre- and post-operative urine samples were collected. Bacterial genomic DNA was extracted. Alpha and beta diversity measurements were calculated and compared. A zero-inflated negative binomial model was utilized to compare taxa abundances between disease status and surgery status. RESULTS: Urine samples were obtained from both cohorts, 69 samples in total: 36 samples were obtained pre-operatively and 33 samples were obtained post-operatively. Ten patients provided both a pre-operative and post-operative urine sample. Twenty-six patients had pathological evidence of LS and 33 patients did not. There was a statistically significant difference in alpha diversity between the pre-operative urine samples of patients with non-LS USD and LS USD, (p = 0.01). There was no significant difference in alpha diversity within post-operative urine samples between patients with non-LS USD and LS USD, (p = 0.1). A significant difference was observed in Weighed UniFrac distances with respect to disease and operative status, (p = 0.001 and 0.002). CONCLUSIONS: LS USD have significant alterations in diversity and differential abundance of urine microbiota compared to non-LS USD controls. These findings could be used to guide further investigations into the role of the urinary microbiome in LS USD pathogenesis, severity of presentation, and stricture recurrence.

Injury Patterns and Outcomes at a Single Pediatric Trauma Center During the Coronavirus Disease 19 Pandemic.

INTRODUCTION: The coronavirus disease 19 (COVID-19) pandemic is reported to have changed injury patterns, prevalence, and outcomes across multiple institutions in the United States. Interpretation of aggregate data is difficult because injury patterns vary between urban and rural hospitals and the implementation of locoregional public health policies and guidelines in response to COVID-19 differed. To prepare our trauma system for future societal shutdowns, we compared injury patterns and outcomes of injured children and adolescents at a single pediatric trauma center before and during the first 2 y of the COVID-19 pandemic. METHODS: We abstracted demographic, injury, and outcome data for injured children and adolescents (age <15 y) who required admission using our hospital trauma registry and the electronic medical record. We compared differences prior to and during the COVID-19 pandemic using univariate analysis. To address confounding variables, we also analyzed in-hospital mortality using a multivariable regression. RESULTS: We observed an increase in the number of injured children requiring admission during the first year of the COVID-19 pandemic compared to the prepandemic era. Among injury types sustained, we observed an increase in firearm and nonfirearm related penetrating injuries (P < 0.001) during the first year, but not the second year, of the COVID-19 pandemic. Controlling for several confounding variables, we also observed an increase in in-hospital mortality (P = 0.04) during the first year of the COVID-19 pandemic. CONCLUSIONS: The psychosocial and socioeconomic burden of the COVID-19 pandemic may have contributed to the rise in penetrating injuries and the odds of in-hospital mortality among a cohort of children and adolescents who were admitted to our hospital following injury. This data may be used to prepare our trauma system for future societal shutdowns through data informed resource utilization.

Evaluation of Missing Prehospital Physiological Values in Injured Children and Adolescents.

INTRODUCTION: Prehospital vital signs and the Glasgow Coma Scale score are often missing in clinical practice and not recorded in trauma databases. Our study aimed to identify factors associated with missing prehospital physiological values, including systolic blood pressure, heart rate, respiratory rate, peripheral oxygen saturation, and Glasgow Coma Scale. METHODS: We used our hospital trauma registry to obtain patient, injury, resuscitation, and transportation characteristics for injured children and adolescents (age <15 y). We evaluated the association of missing documentation of prehospital values with other patient, injury, transportation, and resuscitation characteristics using multivariable regression. We standardized vital sign values using age-adjusted z-scores. RESULTS: The odds of a missing physiological value decreased with age (odds ratio [OR] = 0.9, 95% confidence interval [CI] = 0.9, 0.9) and were higher when prehospital cardiopulmonary resuscitation was required (OR = 3.3, 95% CI = 1.9, 5.7). Among the physiological values considered, we observed the highest odds of missingness of systolic blood pressure, respiratory rate, and oxygen saturation. The odds of observing normal emergency department physiological values were lower when prehospital physiological values were missing (OR = 0.9, 95% CI = 0.9, 1.0; P = 0.04). CONCLUSIONS: Missing prehospital physiological values were associated with younger age and cardiopulmonary resuscitation among the injured children treated at our hospital. Measurement and documentation of physiological variables of patients with these characteristics should be targeted.

Factors Affecting Peripheral Intravenous Catheter Placement During Pediatric Trauma Resuscitation.

INTRODUCTION: Intravenous access is required for resuscitation of injured patients but may be delayed in children because of challenges associated with peripheral intravenous (PIV) catheter placement. Early identification of factors predisposing patients to difficult PIV placement can assist in deciding strategies for timely intravenous access. METHODS: We conducted a retrospective, video-based review of injured children and adolescents treated between April 2018 and May 2019. Patient demographic, physiological, injury, and resuscitation characteristics were obtained from the patient record, including age, race, weight, injury type, Injury Severity Score, initial systolic blood pressure, initial Glasgow Coma Score, intubation status, activation level, and presence of prearrival notification. Video review was used to determine the time to PIV placement, the number of attempts required, the purpose for additional access, and the reason for abandonment of PIV placement. Multivariable regressions were used to determine factors associated with successful placement. RESULTS: During the study period, 154 consented patients underwent attempts at PIV placement in the trauma bay. Placement was successful in 139 (90.3%) patients. Older patients (OR [odds ratio]: 0.9, 95% confidence interval [CI]: 0.9, 0.9) and patients who required the highest level activation response (OR: 0.0, 95% CI: 0.0, 0.3) were less likely to have an attempt at PIV placement abandoned. Children with nonblunt injuries (OR: 11.6, 95% CI: 1.3, 119.2) and pre-existing access (OR: 39.6, 95% CI: 7.0, 350.6) were more likely to have an attempt at PIV placement abandoned. Among patients with successful PIV placement, the time required for establishing PIV access was faster as age increased (-0.5 s, 95% CI: -1.1, -0.0). CONCLUSIONS: Younger age was associated with abandonment of PIV attempts and, when successful, increased time to placement. Strategies to improve successful PIV placement and alternate routes of access should be considered early to prevent treatment delays in younger children.

Discovering interpretable medical process models: A case study in trauma resuscitation.

Understanding the actual work (i.e., "work-as-done") rather than theorized work (i.e., "work-as-imagined") during complex medical processes is critical for developing approaches that improve patient outcomes. Although process mining has been used to discover process models from medical activity logs, it often omits critical steps or produces cluttered and unreadable models. In this paper, we introduce a TraceAlignment-based ProcessDiscovery method called TAD Miner to build interpretable process models for complex medical processes. TAD Miner creates simple linear process models using a threshold metric that optimizes the consensus sequence to represent the backbone process, and then identifies both concurrent activities and uncommon-but-critical activities to represent the side branches. TAD Miner also identifies the locations of repeated activities, an essential feature for representing medical treatment steps. We conducted a study using activity logs of 308 pediatric trauma resuscitations to develop and evaluate TAD Miner. TAD Miner was used to discover process models for five resuscitation goals, including establishing intravenous (IV) access, administering non-invasive oxygenation, performing back assessment, administering blood transfusion, and performing intubation. We quantitively evaluated the process models with several complexity and accuracy metrics, and performed qualitative evaluation with four medical experts to assess the accuracy and interpretability of the discovered models. Through these evaluations, we compared the performance of our method to that of two state-of-the-art process discovery algorithms: Inductive Miner and Split Miner. The process models discovered by TAD Miner had lower complexity and better interpretability than the state-of-the-art methods, and the fitness and precision of the models were comparable. We used the TAD process models to identify (1) the errors and (2)the best locations for the tentative steps in knowledge-driven expert models. The knowledge-driven models were revised based on the modifications suggested by the discovered models. The improved modeling using TAD Miner may enhance understanding of complex medical processes.

The Roles of miRNAs in Predicting Bladder Cancer Recurrence and Resistance to Treatment.

Bladder cancer (BCa) is associated with significant morbidity, with development linked to environmental, lifestyle, and genetic causes. Recurrence presents a significant issue and is managed in the clinical setting with intravesical chemotherapy or immunotherapy. In order to address challenges such as a limited supply of BCG and identifying cases likely to recur, it would be advantageous to use molecular biomarkers to determine likelihood of recurrence and treatment response. Here, we review microRNAs (miRNAs) that have shown promise as predictors of BCa recurrence. MiRNAs are also discussed in the context of predicting resistance or susceptibility to BCa treatment.

MicroRNA-155-5p Targets JADE-1, Promoting Proliferation, Migration, and Invasion in Clear Cell Renal Cell Carcinoma Cells.

Clear cell renal cell carcinoma (ccRCC) incidence has been rising in recent years, with strong association between differential microRNA (miRNA) expression and neoplastic progression. Specifically, overexpression of miR-155-5p has been associated with promoting aggressive cancer in ccRCC and other cancers. In this study, we further investigate the role of this miRNA and one of its protein targets, Jade-1, to better understand the mechanism behind aggressive forms of ccRCC. Jade-1, a tumor suppressor, is stabilized by Von-Hippel Lindau (VHL), which is frequently mutated in ccRCC. Experiments featuring downregulation of miR-155-5p in two ccRCC cell lines (786-O and Caki-1) attenuated their oncogenic potential and led to increased levels of Jade-1. Conversely, knockdown experiments with an anti-Jade-1 shRNA in 786-O and Caki-1 cells showed increased metastatic potential through elevated proliferation, migration, and invasion rates. In a mouse xenograft model, downregulation of miR-155 decreased the rate of tumor implantation and proliferation. Direct interaction between miR-155-5p and Jade-1 was confirmed through a 3'UTR luciferase reporter assay. These findings further elucidate the mechanism of action of miR-155-5p in driving an aggressive phenotype in ccRCC through its role in regulating Jade-1.

Protein Expression Profiles among Lichen Sclerosus Urethral Strictures-Can Urethroplasty Success be Predicted?

PURPOSE: Urethroplasty of lichen sclerosus strictures has a significantly higher failure rate than strictures due to other causes. We sought to determine predictors of urethroplasty failure in men with lichen sclerosus urethral stricture disease by evaluating protein expression profiles. MATERIALS AND METHODS: Urethral tissue was excised from patients with lichen sclerosus who were undergoing urethroplasty of urethral stricture disease at a single institution. A tissue microarray was created with cores from each sample. Immunohistochemistry was performed to compare protein expression related to inflammation, cell cycle disruption, oxidative stress, hormone receptor status and infection. Stricture recurrence was defined by the need for a subsequent unanticipated procedure for urethral stricture disease. RESULTS: We evaluated 50 men with lichen sclerosus urethral stricture disease, including 31 with successful reconstruction and 19 with recurrent stricture. Recurrent strictures expressed lower levels of several inflammatory markers and had a lower Ki-67 mitotic index and significantly higher vascular endothelial growth factor levels than nonrecurrent strictures. CONCLUSIONS: To our knowledge this is the first study to use tissue protein expression to identify risk factors for urethroplasty failure among men with lichen sclerosus urethral stricture disease. Our findings suggest that recurrent lichen sclerosus strictures demonstrate a suppressed inflammatory response, a decreased cell turnover rate, and poor oxygenation and nutrient delivery. Prospective studies are needed to clarify the role of these pathways in the pathophysiology of lichen sclerosus urethral stricture disease, determine whether preoperative biopsy can predict urethroplasty success, help counsel patients and develop future treatments.

Improving quality in colon and rectal surgery through palliative care.

Palliative care is a medical discipline that emphasizes quality of life and can be provided in parallel with recovery-directed treatments in colon and rectal surgery. Palliative care is receiving increasing attention and investigation for its potential to improve quality and outcomes for a wide spectrum of patients by benefiting symptom management, supporting complex health care decision making and facilitating care transitions. Primary palliative care refers to the application of palliative care principles by clinicians of all disciplines whereas specialty palliative care is a multidisciplinary approach and includes a clinician with advanced training and experience.

Insights into the Pathophysiology of Urethral Stricture Disease due to Lichen Sclerosus: Comparison of Pathological Markers in Lichen Sclerosus Induced Strictures vs Nonlichen Sclerosus Induced Strictures.

PURPOSE: We evaluated the pathophysiology of lichen sclerosus and nonlichen sclerosus urethral stricture disease by comparing protein expression related to inflammation, cell cycle disruption, oxidative stress, hormone receptor status and infection. MATERIALS AND METHODS: Tissue samples were collected from the urethral strictures of 81 patients undergoing urethroplasty. Clinical and demographic data were obtained by chart review. After identifying areas pathognomonic for lichen sclerosus a tissue microarray was created with cores from each sample and immunohistochemistry was performed. RESULTS: Patients had similar baseline demographics and comorbidities. Of the 81 strictures 58 were and 23 were not due to lichen sclerosus. Lichen sclerosus strictures were significantly longer and showed higher levels of inflammation. The proportion of T cells which stained positive for CD8 was significantly higher in strictures due to lichen sclerosus (50% vs 13%, p = 0.004). CCL-4 was expressed significantly more in strictures due to lichen sclerosus (76% vs 42%, p = 0.01). Several other inflammatory markers were only found in strictures due to lichen sclerosus. Block-like p16, a surrogate for high risk human papillomavirus infection, and varicella zoster virus were found only in lichen sclerosus urethral stricture disease samples, although both were rare. Epstein-Barr virus RNA was found in significantly more lichen sclerosus samples (37% vs 10%, p = 0.024). CONCLUSIONS: To our knowledge this is the first study to evaluate protein expression in lichen sclerosus urethral stricture disease. These strictures demonstrate increased inflammation compared to nonlichen sclerosus urethral strictures. Markers of oxidative stress, cell cycle dysregulation and the androgen receptor do not appear to be uniquely associated with lichen sclerosus urethral stricture disease. Positive staining for several viruses in samples of lichen sclerosus urethral stricture disease suggests a possible infectious etiology.

Profiling microRNA from nephrectomy and biopsy specimens: predictors of progression and survival in clear cell renal cell carcinoma.

OBJECTIVE: To identify microRNA (miRNA) characteristic of metastatic clear cell renal cell carcinoma (ccRCC) and those indicative of cancer-specific survival (CSS) in nephrectomy and biopsy specimens. We also sought to determine if a miRNA panel could differentiate benign from ccRCC tissue. MATERIALS AND METHODS: RNA was isolated from nephrectomy and kidney biopsy specimens (n = 156 and n = 46, respectively). Samples were grouped: benign, non-progressive, and progressive ccRCC. MiRNAs were profiled by microarray and validated by quantitative reverse transcription-polymerase chain reaction. Biomarker signatures were developed to predict cancer status in nephrectomy and biopsy specimens. CSS was examined using Kaplan-Meier and Cox proportional hazards analyses. RESULTS: Microarray analysis revealed 20 differentially expressed miRNAs comparing non-progressive with progressive tumours. A biomarker signature validated in nephrectomy specimens had a sensitivity of 86.7% and a specificity of 92.9% for differentiating benign and ccRCC specimens. A second signature differentiated non-progressive vs progressive ccRCC with a sensitivity of 93.8% and a specificity of 83.3%. These biomarkers also discriminated cancer status in biopsy specimens. Levels of miR-10a-5p, -10b-5p, and -223-3p were associated with CSS. CONCLUSION: This study identified miRNAs differentially expressed in ccRCC samples; as well as those correlating with CSS. Biomarkers identified in this study have the potential to identify patients who are likely to have progressive ccRCC, and although preliminary, these results may aid in differentiating aggressive and indolent ccRCC based on biopsy specimens.

Treatment Modalities for Non-Muscle Invasive Bladder Cancer: An Updated Review.

The landscape of treatment for non-muscle invasive bladder cancer is rapidly changing. A complete and careful transurethral resection is the mainstay of initial treatment and is followed by intravesical therapy in intermediate or high-risk cases. The standard of care is intravesical BCG. Many alternative or additive approaches to this are being explored. We divided this review into three relevant spaces to consider these novel treatment approaches: (1) low-risk disease, for which intravesical therapy is not usually considered, (2) BCG-naïve disease (i.e., considering alternatives to the standard therapy), and (3) BCG-unresponsive disease. We performed a review of published literature and summarized ongoing trials in the United States. Novel approaches that we explored include surgical techniques for resection, alterations in dwell time for intravesical therapy, delivery method and schedule of intravesical therapies, new intravesical therapy agents, and systemic therapies (especially immunotherapy). These are thoroughly outlined throughout this review article, and the numerous modalities being studied demonstrate significant promise for the future treatment of the expanding space of NMIBC.

Use of Droplet Digital Polymerase Chain Reaction to Identify Biomarkers for Differentiation of Benign and Malignant Renal Masses.

Several microRNAs (miRNAs) have been identified as cell-free biomarkers for detecting renal cell carcinoma (RCC). Droplet digital polymerase chain reaction (ddPCR) is a unique technology for nucleic acid quantification. It has the potential for superior precision, reproducibility, and diagnostic performance in identifying circulating miRNA biomarkers compared to conventional quantitative real-time PCR (qRT-PCR). This study aims to evaluate the performance of ddPCR compared to qRT- PCR in identifying miRNA biomarkers that differentiate malignant from benign renal masses. Potential biomarkers of RCC were identified from a literature review. RNA was extracted from the plasma of 56 patients. All the samples underwent analysis via ddPCR as well as qRT-PCR, and expression levels were recorded for the following miRNAs: miR-93, -144, -210, -221, and -222. Tumors were grouped into low-grade ccRCC, high-grade ccRCC, papillary RCC, and benign masses (primarily angiomyolipoma). The miRNA miR-210 (p = 0.034) and the combination of miRs-210 and miR-222 (p = 0.003) were expressed at significantly higher rates among those with RCC than those with benign masses, as measured by ddPCR. Using the combination of miR-210 and miR-222, ddPCR identified significant differences between the subgroups: papillary RCC versus benign (p = 0.03), low-grade ccRCC versus benign (p = 0.026), and high-grade ccRCC versus benign (p = 0.002). The only significant difference between these subgroups using qRT-PCR was between high-grade ccRCC and benign (p = 0.045). All the AUCs were significant when comparing each RCC subgroup with benign for both PCR technologies. Using a combination of miR-210 and miR-222, ddPCR identified significant differences between benign and malignant renal masses that were not identified as significant by conventional qRT-PCR.

Identification of a gene expression signature of vascular invasion and recurrence in stage I lung adenocarcinoma via bulk and spatial transcriptomics.

Microscopic vascular invasion (VI) is predictive of recurrence and benefit from lobectomy in stage I lung adenocarcinoma (LUAD) but is difficult to assess in resection specimens and cannot be accurately predicted prior to surgery. Thus, new biomarkers are needed to identify this aggressive subset of stage I LUAD tumors. To assess molecular and microenvironment features associated with angioinvasive LUAD we profiled 162 resected stage I tumors with and without VI by RNA-seq and explored spatial patterns of gene expression in a subset of 15 samples by high-resolution spatial transcriptomics (stRNA-seq). Despite the small size of invaded blood vessels, we identified a gene expression signature of VI from the bulk RNA-seq discovery cohort (n=103) and found that it was associated with VI foci, desmoplastic stroma, and high-grade patterns in our stRNA-seq data. We observed a stronger association with high-grade patterns from VI+ compared with VI- tumors. Using the discovery cohort, we developed a transcriptomic predictor of VI, that in an independent validation cohort (n=60) was associated with VI (AUROC=0.86; p=5.42×10-6) and predictive of recurrence-free survival (HR=1.98; p=0.024), even in VI- LUAD (HR=2.76; p=0.003). To determine our VI predictor's robustness to intra-tumor heterogeneity we used RNA-seq data from multi-region sampling of stage I LUAD cases in TRACERx, where the predictor scores showed high correlation (R=0.87, p<2.2×10-16) between two randomly sampled regions of the same tumor. Our study suggests that VI-associated gene expression changes are detectable beyond the site of intravasation and can be used to predict the presence of VI. This may enable the prediction of angioinvasive LUAD from biopsy specimens, allowing for more tailored medical and surgical management of stage I LUAD.

Development and validation of a Bayesian belief network predicting the probability of blood transfusion after pediatric injury.

BACKGROUND: Early recognition and intervention of hemorrhage are associated with decreased morbidity in children. Triage models have been developed to aid in the recognition of hemorrhagic shock after injury but require complete data and have limited accuracy. To address these limitations, we developed a Bayesian belief network, a machine learning model that represents the joint probability distribution for a set of observed or unobserved independent variables, to predict blood transfusion after injury in children and adolescents. METHODS: We abstracted patient, injury, and resuscitation characteristics of injured children and adolescents (age 1 to 18 years) from the 2017 to 2019 Trauma Quality Improvement Project database. We trained a Bayesian belief network to predict blood transfusion within 4 hours after arrival to the hospital following injury using data from 2017 and recalibrated the model using data from 2018. We validated our model on a subset of patients from the 2019 Trauma Quality Improvement Project. We evaluated model performance using the area under the receiver operating characteristic curve and calibration curves and compared performance with pediatric age-adjusted shock index (SIPA) and reverse shock index with Glasgow Coma Scale (rSIG) using sensitivity, specificity, accuracy, and Matthew's correlation coefficient (MCC). RESULTS: The final model included 14 predictor variables and had excellent discrimination and calibration. The model achieved an area under the receiver operating characteristic curve of 0.92 using emergency department data. When used as a binary predictor at an optimal threshold probability, the model had similar sensitivity, specificity, accuracy, and MCC compared with SIPA when only age, systolic blood pressure, and heart rate were observed. With the addition of the Glasgow Coma Scale score, the model has a higher accuracy and MCC than SIPA and rSIG. CONCLUSION: A Bayesian belief network predicted blood transfusion after injury in children and adolescents better than SIPA and rSIG. This probabilistic model may allow clinicians to stratify hemorrhagic control interventions based upon risk. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level III.

Time is tissue: Barriers to timely transfusion after pediatric injury.

ABSTRACT: Strategies to improve outcomes among children and adolescents in hemorrhagic shock have primarily focused on component resuscitation, pharmaceutical coagulation adjuncts, and hemorrhage control techniques. Many of these strategies have been associated with better outcomes in children, but the barriers to their use and the impact of timely use on morbidity and mortality have received little attention. Because transfusion is uncommon in injured children, few studies have identified and described barriers to the processes of using these interventions in bleeding patients, processes that move from the decision to transfuse, to obtaining the necessary blood products and adjuncts, and to delivering them to the patient. In this review, we identify and describe the steps needed to ensure timely blood transfusion and propose practices to minimize barriers in this process. Given the potential impact of time on hemorrhage associated outcomes, ensuring timely intervention may have a similar or greater impact than the interventions themselves.

Functional impairment associated with nonfatal pediatric firearm injuries.

BACKGROUND: Firearm injury is now the leading cause of death for children in the United States. Functional morbidity among survivors also contributes to the public health burden of firearm injury but has not been quantified in children. This study aimed to assess functional impairment among survivors of pediatric firearm injury. METHODS: We analyzed an 8-year (2014-2022) retrospective cohort of children (0-18 years) treated for firearm injuries at 2 urban level 1 pediatric trauma centers. The Functional Status Scale was used to assess functional impairment among survivors at discharge and at follow-up. Functional impairment was defined using multisystem (Functional Status Scale ≥8) and single-system (Functional Status Scale = 7) definitions. RESULTS: The cohort included 282 children with a mean age of 11.1 (standard deviation 4.5) years. In-hospital mortality was 7% (n = 19). Functional impairment (Functional Status Scale ≥8) was present in 9% (n = 24) of children at discharge and in 7% (n = 13/192) at follow-up. Mild impairment in a single domain (Functional Status Scale = 7) was seen in 42% (n = 110) of the cohort at discharge. This impairment persisted to follow-up in most (67%, n = 59/88) of these children. CONCLUSION: Functional impairment at discharge after firearm injury is common among children surviving transport in these trauma centers. These data highlight the added value of non-mortality metrics in assessing the health burden of pediatric firearm injuries. The collective impact of mortality and functional morbidity should be considered when advocating for resources to protect children.

Survival Bias in Pediatric Hemorrhagic Shock: Are We Misrepresenting the Data?

BACKGROUND: Studies of hemorrhage following pediatric injury often use the occurrence of transfusion as a surrogate definition for the clinical need for a transfusion. Using this approach, patients who are bleeding but die before receiving a transfusion are misclassified as not needing a transfusion. In this study, we aimed to evaluate the potential for this survival bias and to estimate its presence among a retrospective observational cohort of children and adolescents who died from injury. METHODS: We obtained patient, injury, and resuscitation characteristics from the 2017 to 2020 Trauma Quality Improvement Program database of children and adolescents (age < 18 years) who arrived with or without signs of life and died. We performed univariate analysis and a multivariable logistic regression to analyze the association between the time to death and the occurrence of transfusion within four hours after hospital arrival controlling for initial vital signs, injury type, body regions injured, and scene versus transfer status. RESULTS: We included 6,063 children who died from either a blunt or penetrating injury. We observed that children who died within 15 minutes had lower odds of receiving a transfusion (odds ratio [OR] = 0.1, 95% CI = 0.1, 0.2) compared to those who survived longer. We estimated that survival bias that occurs when using transfusion administration alone to define hemorrhagic shock may occur in up to 11% of all children who died following a blunt or penetrating injury but less than 1% of all children managed as trauma activations. CONCLUSION: Using the occurrence of transfusion alone may underestimate the number of children who die from uncontrolled hemorrhage early after injury. Additional variables than just transfusion administration are needed to more accurately identify the presence of hemorrhagic shock among injured children and adolescents. LEVEL OF EVIDENCE: Prognostic and Epidemiological, Level III.

Vascular Invasion Predicts Recurrence in Stage IA2-IB Lung Adenocarcinoma but not Squamous Cell Carcinoma.

BACKGROUND: Lymphovascular invasion (LVI) is an adverse prognostic feature in resected stage I non-small cell lung cancer (NSCLC); however, it is unclear if the prognostic significance applies to both lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). MATERIALS AND METHODS: A retrospective review of H&E-stained slides from surgically resected AJCC 8th ed. stage IA2-IB LUAD (n = 344) and LUSC (n = 102) from two institutions was performed. LVI was defined as either lymphatic (LI) or vascular (VI) invasion. Outcomes were assessed by 5-year recurrence-free survival (RFS) estimates using the Kaplan-Meier method. RESULTS: The cohorts of LUAD and LUSC showed no significant differences in 5-year RFS (81% each), stage, age, race, or surgical procedure. The presence of LVI, VI, and LI was predictive of 5-year RFS for LUAD (LVI + 71% vs. LVI - 92%, P < 0.001; VI + 64% vs. VI - 90%, P < 0.001; LI + 75% vs. LI - 84%, P = 0.030) but not LUSC (LVI + 84% vs. LVI - 79%, P = 0.740; VI + 83% vs. VI- 80%, P = 0.852; LI + 84% vs. LI - 81%, P = 0.757). Among LUAD with LVI, VI was a stronger predictor of 5-year RFS than the remaining subset of VI-LI + tumors (64% vs. 87%, P = 004). Subset analysis of LI among LUAD stratified by VI showed no significant prognostic advantage to adding LI for risk stratification (VI-LI + 87% vs. VI-LI - 92%, P = 0.347 & VI+LI + 62% vs. VI + LI- 66%, P = 0.422). VI was present in 36% of LUAD. CONCLUSION: Vascular invasion is a strong predictor of recurrence in stage IA2-IB LUAD but not in LUSC. Adjuvant therapy trials should be directed at this subgroup.