A decade of firearm injuries: Have we improved?

BACKGROUND: Firearm injuries are a growing public health issue, with marked increases coinciding with the coronavirus disease 2019 (COVID-19) pandemic. This study evaluates temporal trends over the past decade, hypothesizing that despite a growing number of injuries, mortality would be unaffected. In addition, the study characterizes the types of centers affected disproportionately by the reported firearm injury surge in 2020. METHODS: Patients 18 years and older with firearm injuries from 2011 to 2020 were identified retrospectively using the National Trauma Data Bank (NTDB®). Trauma centers not operating for the entirety of the study period were excluded to allow for temporal comparisons. Joinpoint regression and risk-standardized mortality ratios (SMR) were used to evaluate injury counts and adjusted mortality over time. Subgroup analysis was performed to describe centers with the largest increases in firearm injuries in 2020. RESULTS: A total of 238,674 patients, treated at 420 unique trauma centers, met inclusion criteria. Firearm injuries increased by 31.1% in 2020, compared to an annual percent change of 2.4% from 2011 to 2019 ( p = 0.01). Subset analysis of centers with the largest changes in firearm injuries in 2020 found that they were more often Level I centers, with higher historic trauma volumes and percentages of firearm injuries ( p < 0.001). Unadjusted mortality decreased by 0.9% from 2011 to 2020, but after controlling for demographics, injury characteristics and physiology, there was no difference in adjusted mortality over the same time period. However, among patients with injury severity scores ≥25, adjusted mortality improved compared with 2011 (SMR of 0.950 in 2020; 95% confidence interval, 0.916-0.986). CONCLUSION: Firearm injuries pose an increasing burden to trauma systems, with Level I and high-volume centers seeing the largest growth in 2020. Despite increasing numbers of firearm injuries, mortality has remained unchanged over the past decade. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Evaluation of coagulopathy in cirrhotic patients: A scoping review of the utility of viscoelastic testing.

BACKGROUND: Cirrhosis causes significant coagulopathy. Traditional coagulation tests may not accurately measure coagulopathy in well-compensated patients with cirrhosis. Viscoelastic tests are functional tests that may better assess coagulopathy in cirrhotic patients. METHODS: We searched PubMed, ScienceDirect, Google Scholar, and grey literature using terms meaning viscoelastic testing and cirrhosis. After reviewing over 500 titles and abstracts, 40 full-text papers met inclusion criteria. RESULTS: Twenty-two papers found viscoelastic testing was a better indicator of baseline coagulation than traditional testing in cirrhosis. Nineteen additional papers evaluated the utility of peri-procedural viscoelastic testing and found they led to a reduction in blood product administration without increasing risk of hemorrhage, thrombotic events, or other complications. CONCLUSIONS: The usage of viscoelastic testing in patients with cirrhosis allows for better assessment of coagulopathy, resulting in improved outcomes. Educating physicians to optimize care of this high-risk group is necessary to further improve their treatment.

Examining the relationship between autism spectrum disorder and neural tube defects.

Folate and vitamin B12 deficiencies have been strongly associated with neural tube defects, preliminary research suggests folate and B12 deficiency may also be associated with autism spectrum disorder (ASD). We examined the association between neural tube defects and ASD as a further avenue to examine the hypothesis that ASD is related to maternal folate and B12 deficiency during pregnancy. A retrospective case-control study was performed using the Military Health System Data Repository. Cases and matched controls were followed from birth until at least 6 months after their first autism diagnosis. International Classification of Diseases, 9th Revision, codes were used to identify neural tube defects in the health records. A total of 8760 cases between the ages of 2 and 18 years were identified. The prevalence of any neural tube defect was 0.11% in children without ASD and 0.64% in children with ASD. Children with autism were over 6 times as likely to have a neural tube defect. The increased odds of neural tube defect in children diagnosed with ASD, found through our methodology, supports prior studies. Although additional studies are needed to elucidate the relationship between ASD and maternal folate and vitamin B12 deficiency during pregnancy this study supports their use during pregnancy.

Association of Gonadotropin-Releasing Hormone Analogue Use With Subsequent Use of Gender-Affirming Hormones Among Transgender Adolescents.

Importance: Gonadotropin-releasing hormone analogue (GnRHa) use during puberty improves mental health among transgender and gender-diverse (TGD) adolescents. In previous studies, most (96.5%-98.1%) TGD adolescents who started GnRHa subsequently started gender-affirming hormones (GAH), raising concerns that GnRHa use promotes later use of GAH. Objective: To determine whether GnRHa use among TGD adolescents is associated with increased subsequent GAH use. Design, Setting, and Participants: This is a retrospective cohort study of administrative records collected between 2009 and 2018. The current analysis was completed in August 2022. Participants were enrolled in the US Military Healthcare System (MHS) with an initial TGD-related encounter occurring between ages 10 and 17 years. Exposures: GnRHa use. Main Outcomes and Measures: Initiation of GAH. Results: The 434 patients were a mean (SD) of 15.4 (1.6) years old at the time of their first TGD-related encounter; 312 (71.9%) were assigned female at birth, and 300 (69.1%) had an enlisted insurance sponsor. GnRHa use was more common among patients who were assigned male at birth (28 patients [23.0%]) than those assigned female (42 patients [13.5%]), but GAH use was not. Socioeconomic status was not associated with GnRHa or GAH use. Compared with older patients (aged 14-17 years), those who were younger (aged 10-13 years) at the time of the initial TGD-related encounter had a higher rate of GnRHa use (32 patients [57.1%] vs 38 patients [10.1%]) and a longer median time to starting GAH. The median interval from the date of the initial encounter to starting GAH decreased over time, from 2.3 years (95% CI, 1.7-2.8 years) between October 2009 and December 2014 to 0.6 years (95% CI, 0.5-0.6 years) between September 2016 and April 2018. Patients who were prescribed GnRHa had a longer median time to starting GAH (1.8 years; 95% CI, 1.1-2.4 years) than patients who were not (1.0 years; 95% CI, 0.8-1.2 years) and were less likely to start GAH during the 6 years after their first TGD-related encounter (hazard ratio, 0.52; 95% CI, 0.37-0.71). Among 54 younger (aged 10-13 years) patients who were not eligible to start GAH at their first encounter, GnRHa use was associated with a longer median time to starting GAH, but age at the first TGD-related visit was not. Conclusions and Relevance: In this cohort study of TGD adolescents, GnRHa use was not associated with increased subsequent GAH use. These findings suggest that clinicians can offer the benefits of GnRHa treatment without concern for increasing rates of future GAH use.

High resuscitative endovascular balloon occlusion of the aorta procedural volume is associated with improved outcomes: An analysis of the AORTA registry.

BACKGROUND: The use of resuscitative endovascular balloon occlusion of the aorta (REBOA) is controversial. We hypothesize that REBOA outcomes are improved in centers with high REBOA utilization. METHODS: We examined the Aortic Occlusion in Resuscitation for Trauma and Acute Care Surgery registry over a 5-year period (2014-2018). Resuscitative endovascular balloon occlusion of the aorta outcomes were analyzed by stratifying institutions into low-volume (<10), average-volume (11-30), and high-volume (>30) deployment centers. A multivariable model adjusting for volume group, mechanism of injury, signs of life, systolic blood pressure at initiation, operator level, device type, zone of placement, and hemodynamic response to aortic occlusion was created to analyze REBOA mortality and REBOA-related complications. RESULTS: Four hundred ninety-five REBOA placements were included. High-volume centers accounted for 63%, while low accounted for 13%. High-volume institutions were more likely to place a REBOA in the emergency department (81% vs. 63% low volume, p = 0.003), had a lower mean systolic blood pressure at insertion (53 ± 38 vs. 64 ± 40, p = 0.001), and more Zone I deployments (64% vs. 55%, p = 0.002). Median time from admission to REBOA placement was significantly less in patients treated at high-volume centers (15 [7-30] minutes vs. 35 [20-65] minutes, p = 0.001). Resuscitative endovascular balloon occlusion of the aorta mortality was significantly higher at low-volume centers (67% vs. 57%; adjusted odds ratio, 1.29; adj p = 0.040), while average- and high-volume centers were similar. Resuscitative endovascular balloon occlusion of the aorta complications were less frequent at high-/average-volume centers, but did not reach statistical significance (adj p = 0.784). CONCLUSION: Resuscitative endovascular balloon occlusion of the aorta survival is increased at high versus low utilization centers. Increased experience with REBOA may be associated with earlier deployment and subsequently improved patient outcomes. LEVEL OF EVIDENCE: Therapeutic/Care Management, level IV.

Increasing age is associated with worse outcomes in elderly patients with severe liver injury.

While the incidence of geriatric trauma continues to increase, outcomes following severe blunt liver injury (BLI) are unknown. We sought to investigate independent predictors of mortality among elderly trauma patients with severe BLI. A retrospective study of the NTDB (2014-15) identified patients with isolated, high-grade BLI. Patients were stratified into two groups, non-elderly (<65 years) and elderly (≥65 years), and then two management groups: operative within 24 h of admission and non-operative. Demographics and outcomes were compared. Multivariable logistic regression was used to estimate association with mortality. A total of 1133 patients met our inclusion criteria. 107 patients required surgery and 1011 patients were managed non-operatively. Age was independently associated with mortality (AOR 1.04, p < .001). For patients <65 years, need for operative intervention was associated with a 55 times greater likelihood of death (AOR 55.1, p < .001). In patients ≥65 years, operative intervention was associated with a 122 times greater likelihood of death (AOR 122.09, p = .005). Age is independently associated with mortality in patients with high grade BLI.

Is trauma center designation associated with disparities in discharge to rehabilitation centers among elderly patients with Traumatic Brain Injury?

BACKGROUND: We sought to evaluate the role of trauma center designation in the association of race and insurance status with disposition to rehabilitation centers among elderly patients with Traumatic Brain Injury (TBI). METHODS: The National Trauma Data Bank (2014-2015) was used to identify elderly (age ≥ 65) patients with isolated moderate to severe blunt TBI who survived to discharge. Race, insurance status, and outcomes were stratified by trauma center designation and compared. RESULTS: 3,292 patients met the inclusion criteria. Black patients were 1.5 times less likely (AOR 0.64, p = 0.01) and Latino patients were 1.7 times less likely (AOR 0.58, p = 0 0.007) to be discharged to rehabilitation centers as compared with White patients. Asian patients at Level I hospitals were more likely to be discharged to rehabilitation centers if they had private vs. non-private insurance (42.9% versus 12.7%, p = 0.01). CONCLUSION: Black and Latino patients were less likely to be discharged to rehabilitation centers compared to White patients. The etiology of these disparities deserves further study.

Factors Affecting Pediatric Dyslipidemia Screening and Treatment.

Identification and management of dyslipidemia in childhood can reduce future cardiovascular risk. We performed a retrospective cohort study of children ages 2 to 18 years during 2009 to 2013 to evaluate factors that affect screening and treatment of pediatric dyslipidemia related to 2011 National Heart, Lung, and Blood Institute (NHLBI) guidelines. Logistic regression analysis determined the impact of NHLBI-identified factors on odds of being screened, elevated low-density lipoprotein cholesterol (LDL-C), and receiving pharmacotherapy. A total of 1 736 032 children were included; 113 780 (6.6%) were screened for dyslipidemia. Screening in 9 to 11 year olds increased from 2009 to 2012. Of children screened, 18 801 (16.5%) had elevated LDL-C; 425 (2.3%) were treated pharmacologically. Parental dyslipidemia, diabetes mellitus, chronic kidney disease, Kawasaki disease, human immunodeficiency virus infection, nephrotic syndrome, liver, thyroid, and other endocrine disorders increased odds of screening. Older age, nephrotic syndrome, chronic kidney disease, diabetes mellitus, and hypertension increased odds of having elevated LDL-C and receiving treatment. Pediatric dyslipidemia screening rates remain low.

A Founder Mutation in VPS11 Causes an Autosomal Recessive Leukoencephalopathy Linked to Autophagic Defects.

Genetic leukoencephalopathies (gLEs) are a group of heterogeneous disorders with white matter abnormalities affecting the central nervous system (CNS). The causative mutation in ~50% of gLEs is unknown. Using whole exome sequencing (WES), we identified homozygosity for a missense variant, VPS11: c.2536T>G (p.C846G), as the genetic cause of a leukoencephalopathy syndrome in five individuals from three unrelated Ashkenazi Jewish (AJ) families. All five patients exhibited highly concordant disease progression characterized by infantile onset leukoencephalopathy with brain white matter abnormalities, severe motor impairment, cortical blindness, intellectual disability, and seizures. The carrier frequency of the VPS11: c.2536T>G variant is 1:250 in the AJ population (n = 2,026). VPS11 protein is a core component of HOPS (homotypic fusion and protein sorting) and CORVET (class C core vacuole/endosome tethering) protein complexes involved in membrane trafficking and fusion of the lysosomes and endosomes. The cysteine 846 resides in an evolutionarily conserved cysteine-rich RING-H2 domain in carboxyl terminal regions of VPS11 proteins. Our data shows that the C846G mutation causes aberrant ubiquitination and accelerated turnover of VPS11 protein as well as compromised VPS11-VPS18 complex assembly, suggesting a loss of function in the mutant protein. Reduced VPS11 expression leads to an impaired autophagic activity in human cells. Importantly, zebrafish harboring a vps11 mutation with truncated RING-H2 domain demonstrated a significant reduction in CNS myelination following extensive neuronal death in the hindbrain and midbrain. Thus, our study reveals a defect in VPS11 as the underlying etiology for an autosomal recessive leukoencephalopathy disorder associated with a dysfunctional autophagy-lysosome trafficking pathway.

Prevalence of Diagnosed Sleep Disorders and Related Diagnostic and Surgical Procedures in Children with Autism Spectrum Disorders.

OBJECTIVE: Sleep disorders are common and important comorbid conditions in children with autism spectrum disorder (ASD) and can contribute to cognitive and behavioral problems. Sleep-disordered breathing (SDB) is a diagnosable and treatable cause of behavioral problems in children. We aimed to quantify the relative risk for children with ASD versus controls of being diagnosed with sleep disorders including SDB and undergoing related diagnostic and surgical procedures. METHOD: This retrospective case-cohort study included 48,762 children with ASD aged 2 to 18 years enrolled in the military health system (MHS) from 2000 to 2013. Children with ASD were matched 1:5 by birthdate, sex, and enrollment time to children without an ASD diagnosis. The MHS database was queried for International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for sleep disorders or ICD-9-CM and Current Procedural Terminology codes for diagnostic and surgical procedures. Relative risks (RR) and 95% confidence intervals (CI) were determined with binary Poisson regression conditional on the match and adjusting for confounders. RESULTS: Children with ASD were at higher risk of receiving any sleep disorder diagnosis (RR: 1.97 [95% CI, 1.91-2.02]) including SDB (RR: 1.96 [95% CI, 1.88-2.05]). Children with ASD also were at increased risk of undergoing polysomnography (RR: 3.74 [95% CI, 3.56-3.93]) and sleep disorder-related surgery (RR: 1.50 [95% CI, 1.46-1.54]). CONCLUSION: Children with ASD are more likely to be given a sleep disorder diagnosis including SDB and are more likely to undergo related diagnostic and surgical procedures compared with controls without ASD.

A Comprehensive Strategy for Accurate Mutation Detection of the Highly Homologous PMS2.

Germline mutations in the DNA mismatch repair gene PMS2 underlie the cancer susceptibility syndrome, Lynch syndrome. However, accurate molecular testing of PMS2 is complicated by a large number of highly homologous sequences. To establish a comprehensive approach for mutation detection of PMS2, we have designed a strategy combining targeted capture next-generation sequencing (NGS), multiplex ligation-dependent probe amplification, and long-range PCR followed by NGS to simultaneously detect point mutations and copy number changes of PMS2. Exonic deletions (E2 to E9, E5 to E9, E8, E10, E14, and E1 to E15), duplications (E11 to E12), and a nonsense mutation, p.S22*, were identified. Traditional multiplex ligation-dependent probe amplification and Sanger sequencing approaches cannot differentiate the origin of the exonic deletions in the 3' region when PMS2 and PMS2CL share identical sequences as a result of gene conversion. Our approach allows unambiguous identification of mutations in the active gene with a straightforward long-range-PCR/NGS method. Breakpoint analysis of multiple samples revealed that recurrent exon 14 deletions are mediated by homologous Alu sequences. Our comprehensive approach provides a reliable tool for accurate molecular analysis of genes containing multiple copies of highly homologous sequences and should improve PMS2 molecular analysis for patients with Lynch syndrome.

Molecular characterization of two anthranilate synthase alpha subunit genes in Camptotheca acuminata.

The potent anticancer and antiviral compound camptothecin (CPT) is a monoterpene indole alkaloid produced by Camptotheca acuminata. In order to investigate the biosynthetic pathway of CPT, we studied the early indole pathway, a junction between primary and secondary metabolism, which generates tryptophan for both protein synthesis and indole alkaloid production. We cloned and characterized the alpha subunit of anthranilate synthase (ASA) from Camptotheca (designated CaASA), catalyzing the first committed reaction of the indole pathway. CaASA is encoded by a highly conserved gene family in Camptotheca. The two CaASA genes are differentially regulated. The level of CaASA2 is constitutively low in Camptotheca and was found mainly in the reproductive tissues in transgenic tobacco plants carrying the CaASA2 promoter and beta-glucuronidase gene fusion. CaASA1 was detected to varying degrees in all Camptotheca organs examined and transiently induced to a higher level during seedling development. The spatial and developmental regulation of CaASA1 paralleled that of the previously characterized Camptotheca gene encoding the beta subunit of tryptophan synthase as well as the accumulation of CPT. These data suggest that CaASA1, rather than CaASA2, is responsible for synthesizing precursors for CPT biosynthesis in Camptotheca and that the early indole pathway and CPT biosynthesis are coordinately regulated.