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These NCCN Guidelines Insights focus on some of the major updates to the 2014 NCCN Guidelines for Thyroid Carcinoma. Kinase inhibitor therapy may be used to treat thyroid carcinoma that is symptomatic and/or progressive and not amenable to treatment with radioactive iodine. Sorafenib may be considered for select patients with metastatic differentiated thyroid carcinoma, whereas vandetanib or cabozantinib may be recommended for select patients with metastatic medullary thyroid carcinoma. Other kinase inhibitors may be considered for select patients with either type of thyroid carcinoma. A new section on "Principles of Kinase Inhibitor Therapy in Advanced Thyroid Cancer" was added to the NCCN Guidelines to assist with using these novel targeted agents.

Concomitant inhibition of multiple cancer-driving kinases is an established strategy to improve the durability of clinical responses to targeted therapies. The difficulty of discovering kinase inhibitors with an appropriate multitarget profile has, however

Mice are a widely utilized in vivo model for translational salivary gland research but must be used with caution. Specifically, mouse salivary glands are similar in many ways to human salivary glands (i.e., in terms of their anatomy, histology, and physiology) and are both readily available and relatively easy and affordable to maintain. However, there are some significant differences between the two organisms, and by extension, the salivary glands derived from them must be taken into account for translational studies. The current review details pertinent similarities and differences between human and mouse salivary glands and offers practical guidelines for using both for research purposes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: In a cohort that spanned all of childhood and suffered equivalent types of traumas, the authors examined diagnostic validity and risk factors for posttraumatic stress disorder (PTSD). For older children, parent-child agreement was investigated. METHOD: Sixty-two children ages 0-18 years who were hospitalized with injuries were assessed 2 months later for PTSD. Mothers were interviewed, and concurrent interviews were conducted with 24 adolescents. RESULTS: Children did not attain the DSM-IV threshold of three criterion C items until age 7. The 0-6-year-old group had significantly fewer criterion C symptoms (mean=0.43) than the 12-18-year-olds (mean=1.17). The impact of altering thresholds for criteria C and D was examined. Older children reported symptoms meeting criterion B significantly more often (79.2%) than parents (45.8%). Combined parent-child reports yielded significantly more symptoms and higher rates for criteria B, C, and D (almost a twofold increase) and for the overall diagnosis (37.5%) than parent report alone (4.2%). This 8.9-fold increase in diagnosis from combined reports suggests that the diagnostic rates for children who cannot make self-reports may greatly underestimate the true numbers. The interaction between pretrauma externalizing behavior and witnessing a threat to a caregiver had a significant effect on the total number of PTSD symptoms. CONCLUSIONS: These findings provide additional support for lowering the requirement of three criterion C symptoms for preschool children and raise questions about the appropriateness of this threshold for prepubertal children. The validity of studies that do not assess symptoms with combined parent and child reports is limited. [ABSTRACT FROM AUTHOR]

Empyema resulting as a complication of penetrating diaphragmatic injuries is a subject that requires further investigation, and the aim of this study was to determine the risk factors associated with empyema in patients with penetrating trauma. Consecutive adult trauma patients from a level 1 trauma center were searched for penetrating diaphragm injuries. Data were collected on patient demographics, pre-existing conditions, injury type and severity, hospital interventions, in-hospital complications, and outcomes. Patients were stratified by empyema formation and univariant analyses were performed. 164 patients were identified, and 17 patients (10.4%) developed empyema. Empyema was associated with visible abdominal contamination (35.3% vs 15%, P = .04), thoracotomy (35.5% vs 13.6%, P = .03), pneumonia (41.2% vs 14.3%, P = .01), sepsis (35.3% vs 8.8%, P = .006), increased hospital length of stay (25.5 vs 10.1 days, p =<.001), increased intensive care unit length of stay (9.6 vs 4.3 days, P = .01), and decreased in-hospital mortality (0% vs 20.4%, P = .04)., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This study presents data on pre-trauma steroid use, a topic underrepresented in the trauma literature. Long-term steroid use has been linked to impaired wound healing, compromised immune responses, and hindrance of bone healing, alongside the potential for adrenal insufficiency during traumatic events. The aim of this study was to conduct a retrospective analysis of clinical outcomes for trauma patients with chronic steroid use. Examining adult trauma cases with pre-trauma steroid use at a level 1 trauma center (January 2016-September 2023), we identified 18 patients (58.6 ± 19.4 years, 55.6% males). All were on prednisone prior to trauma activation and 66.7% had autoimmune disease. Complications included orthopedic fractures (72.2%), ICU admissions (16.7%), and low mortality (5.6%). Future larger, multi-center studies are needed to determine the impact of immunosuppression and pre-trauma steroids on clinical outcomes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Extracorporeal membrane oxygenation (ECMO) is a cardiopulmonary bypass device commonly used to treat cardiac arrest in children. The American Heart Association guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiovascular care recommend using amiodarone as a first-line agent to treat ventricular arrhythmias in children with cardiac arrest. However, there are no dosing recommendations for amiodarone to treat ventricular arrhythmias in pediatric patients on ECMO. Amiodarone has a high propensity for adsorption to the ECMO components due to its physicochemical properties leading to altered pharmacokinetics (PK) in ECMO patients. The change in amiodarone PK due to interaction with ECMO components may result in a difference in optimal dosing in patients on ECMO when compared with non-ECMO patients. To address this clinical knowledge gap, a physiologically-based pharmacokinetic model of amiodarone was developed in adults and scaled to children, followed by the addition of an ECMO compartment. The pediatric model included ontogeny functions of cytochrome P450 (CYP450) enzyme maturation across various age groups. The ECMO compartment was parameterized using the adsorption data of amiodarone obtained from ex vivo studies. Model predictions captured observed concentrations of amiodarone in pediatric patients with ECMO well with an average fold error between 0.5 and 2. Model simulations support an amiodarone intravenous (i.v) bolus dose of 22 mg/kg (neonates), 13 mg/kg (infants), 8 mg/kg (children), and 6 mg/kg (adolescents). This PBPK modeling approach can be applied to explore the dosing of other drugs used in children on ECMO., (© 2024 The Author(s). CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Introduction: The United States has one of the highest rates of gun violence and mass shootings. Timely medical attention in such events is critical. The objective of this study was to assess geographic disparities in mass shootings and access to trauma centers., Methods: Data for all Level I and II trauma centers were extracted from the American College of Surgeons and the Trauma Center Association of America registries. Mass shooting event data (4+ individuals shot at a single event) were taken from the Gun Violence Archive between 2014 and 2018., Results: A total of 564 trauma centers and 1672 mass shootings were included. Ratios of the number of mass shootings vs trauma centers per state ranged from 0 to 11.0 mass shootings per trauma center. States with the greatest disparity (highest ratio) included Louisiana and New Mexico., Conclusion: States in the southern regions of the US experience the greatest disparity due to a high burden of mass shootings with less access to trauma centers. Interventions are needed to increase access to trauma care and reduce mass shootings in these medically underserved areas., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Loneliness may exacerbate poor health outcomes particularly among cancer survivors during the COVID-19 pandemic. Little is known about the risk factors of loneliness among cancer survivors. We evaluated the risk factors of loneliness in the context of COVID-19 pandemic-related prevention behaviors and lifestyle/psychosocial factors among cancer survivors. Cancer survivors (n = 1471) seen at Huntsman Cancer Institute completed a survey between August-September 2020 evaluating health behaviors, medical care, and psychosocial factors including loneliness during COVID-19 pandemic. Participants were classified into two groups: 'lonely' (sometimes, usually, or always felt lonely in past month) and 'non-lonely' (never or rarely felt lonely in past month). 33% of cancer survivors reported feeling lonely in the past month. Multivariable logistic regression showed female sex, not living with a spouse/partner, poor health status, COVID-19 pandemic-associated lifestyle factors including increased alcohol consumption and marijuana/CBD oil use, and psychosocial stressors such as disruptions in daily life, less social interaction, and higher perceived stress and financial stress were associated with feeling lonely as compared to being non-lonely (all p < 0.05). A significant proportion of participants reported loneliness, which is a serious health risk among vulnerable populations, particularly cancer survivors. Modifiable risk factors such as unhealthy lifestyle behaviors and psychosocial stress were associated with loneliness. These results highlight the need to screen for unhealthy lifestyle factors and psychosocial stressors to identify cancer survivors at increased risk of loneliness and to develop effective management strategies., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The standard for managing traumatic pneumothorax (PTX), hemothorax (HTX), and hemopneumothorax (HPTX) has historically been large-bore (LB) chest tubes (>20-Fr). Previous studies have shown equal efficacy of small-bore (SB) chest tubes (≤19-Fr) in draining PTX and HTX/HPTX. This study aimed to evaluate provider practice patterns, treatment efficacy, and complications related to the selection of chest tube sizes for patients with thoracic trauma., Methods: A retrospective chart review was performed on adult patients who underwent tube thoracostomy for traumatic PTX, HTX, or HPTX at a Level 1 Trauma Center from January 2016 to December 2021. Comparison was made between SB and LB thoracostomy tubes. The primary outcome was indication for chest tube placement based on injury pattern. Secondary outcomes included retained hemothorax, insertion-related complications, and duration of chest tube placement. Univariate and multivariate analyses were performed., Results: Three hundred and forty-one patients were included and 297 (87.1%) received LB tubes. No significant differences were found between the groups concerning tube failure and insertion-related complications. LB tubes were more frequently placed in patients with penetrating MOI, higher average ISS, and higher average thoracic AIS. Patients who received LB chest tubes experienced a higher incidence of retained HTX., Discussion: In patients with thoracic trauma, both SB and LB chest tubes may be used for treatment. SB tubes are typically placed in nonemergent situations, and there is apparent provider bias for LB tubes. A future randomized clinical trial is needed to provide additional data on the usage of SB tubes in emergent situations., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Traumatic abdominal wall hernias are a rare complication of high energy blunt trauma. There exist several studies evaluating and outlining potential management options but still no generalized consensus on management. This series was meant to evaluate the diagnosis and management of traumatic abdominal wall hernias. A prospectively maintained database was used to identify patients with TAWH from 2021 to 2022. The primary outcome was operative management. Secondary outcomes included: time to diagnosis and post-operative outcomes. Of the 19 patients in this case series, 100% (n = 19/19) were secondary to blunt trauma with a mean ISS of 21. Exploratory laparotomy was performed in 17 cases. 14 cases had concomitant traumatic injuries to visceral structures. Complications were found in nearly half of the patients with 3 experiencing wound dehiscence. Future studies should be aimed at standardizing management approach taking into account nature of the mechanism and concomitant injuries., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Fibula free flaps (FFF) are one of the most common bony flaps utilized. This paper describes a quality improvement project aimed at increasing early ambulation., Methods: A review of FFF patients at an academic hospital was completed (2014-2023). In 2018, an institutional change to encourage early ambulation without placement of a boot was made. Changes in hospital disposition and physical therapy outcomes were evaluated., Results: A total of 168 patients underwent FFF reconstruction. There was a statistically significant lower length of stay in Group 2 (early ambulation, no boot) (8.1 vs. 9.4; p = 0.04). A higher rate of discharge to a skilled nursing facility was noted in Group 1 (delayed ambulation with boot) (21.3% vs. 11.9%; p = 0.009). A higher proportion of patients in Group 2 demonstrated independence during bed mobility, transfers, and gait (p < 0.05)., Conclusions: Early ambulation without boot placement after FFF is associated with decreased length of hospital stay, improved disposition to home and physical therapy outcomes., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Objective: Primary hyperparathyroidism (PHPT) affects approximately 0.86% of the population, with surgical resection as the treatment of choice. A 4D computed tomography (CT) is a highly effective tool in localizing parathyroid adenomas; however, there is currently no defined role for 4D CT when stratified against ultrasonography (USG) and nuclear medicine Technetium Sestamibi SPECT/CT (SES) imaging., Study Design: Retrospective Study., Setting: University Hospital., Methods: All patients who underwent parathyroidectomy for PHPT between 2014 and 2019 at a single institution were reviewed. Patients who had a 4D CT were included. We compared outcomes of 4D CT as a second line imaging modality to those of USG and SES as first line modalities. An imaging algorithm was proposed based on these findings., Results: There were 84 patients identified who had a 4D CT after unsuccessful first line imaging. A 4D CT localized parathyroid adenoma to the correct quadrant in 64% of cases, and to the correct laterality in 75% of cases. Obese patients had significantly lower rates of adenoma localization with USG (33.4%), compared to non-obese patients (67.5%; P  = .006). In determining multigland disease the sensitivity of 4D CT was 86%, while the specificity was 87%., Conclusions: A 4D CT has impressive rates of accurate localization of parathyroid adenomas; however due to the radiation exposure involved, it should remain a second line imaging modality. PHPT patients should first be evaluated with USG, with 4D CT used if this is unsuccessful and patients are greater than 40 years old, have a high BMI, or are having revision surgery., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Optimal treatment of infants with many renally cleared drugs must account for maturational differences in renal transporter (RT) activity. Pediatric physiologically-based pharmacokinetic (PBPK) models may incorporate RT activity, but this requires ontogeny profiles for RT activity in children, especially neonates, to predict drug disposition. Therefore, RT expression measurements from human kidney postmortem cortical tissue samples were normalized to represent a fraction of mature RT activity. Using these data, maximum likelihood estimated the distributions of RT activity across the pediatric age spectrum, including preterm and term neonates. PBPK models of four RT substrates (acyclovir, ciprofloxacin, furosemide, and meropenem) were evaluated with and without ontogeny profiles using average fold error (AFE), absolute average fold error (AAFE), and proportion of observations within the 5-95% prediction interval. Novel maximum likelihood profiles estimated ontogeny distributions for the following RT: OAT1, OAT3, OCT2, P-gp, URAT1, BCRP, MATE1, MRP2, MRP4, and MATE-2 K. Profiles for OAT3, P-gp, and MATE1 improved infant furosemide and neonate meropenem PBPK model AFE from 0.08 to 0.70 and 0.53 to 1.34 and model AAFE from 12.08 to 1.44 and 2.09 to 1.36, respectively, and improved the percent of data within the 5-95% prediction interval from 48% to 98% for neonatal ciprofloxacin simulations, respectively. Even after accounting for other critical population-specific maturational differences, novel RT ontogeny profiles substantially improved neonatal PBPK model performance, providing validated estimates of maturational differences in RT activity for optimal dosing in children., (© 2023 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Objectives: Patients with sepsis are at significant risk for multiple organ dysfunction, including the lungs and kidneys. To manage the morbidity associated with kidney impairment, continuous renal replacement therapy (CRRT) may be required. The extent of anakinra pharmacokinetics in CRRT remains unknown. The objectives of this study were to investigate the anakinra-circuit interaction and quantify the rate of removal from plasma., Design: The anakinra-circuit interaction was evaluated using a closed-loop ex vivo CRRT circuit. CRRT was performed in three phases based on the method of solute removal: 1) hemofiltration, 2) hemodialysis, and 3) hemodiafiltration. Standard control samples of anakinra were included to assess drug degradation., Setting: University research laboratory., Patients: None., Interventions: Anakinra was administered to the CRRT circuit and serial prefilter blood samples were collected along with time-matched control and hemofiltrate samples. Each circuit was run in triplicate to assess inter-run variability. Concentrations of anakinra in each reference fluid were measured by enzyme-linked immunosorbent assay. Transmembrane filter clearance was estimated by the product of the sieving coefficient/dialysate saturation constant and circuit flow rates., Measurements and Main Results: Removal of anakinra from plasma occurred within minutes for each CRRT modality. Average drug remaining (%) in plasma following anakinra administration was lowest with hemodiafiltration (34.9%). The average sieving coefficient was 0.34, 0.37, and 0.41 for hemodiafiltration, hemofiltration, and hemodialysis, respectively. Transmembrane clearance was fairly consistent across each modality with the highest during hemodialysis (5.53 mL/min), followed by hemodiafiltration (4.99 mL/min), and hemofiltration (3.94 mL/min). Percent drug remaining within the control samples (93.1%) remained consistent across each experiment, indicating negligible degradation within the blood., Conclusions: The results of this analysis are the first to demonstrate that large molecule therapeutic proteins such as anakinra, are removed from plasma with modern CRRT technology. Current dosing recommendations for patients with severe renal impairment may result in subtherapeutic anakinra concentrations in those receiving CRRT., Competing Interests: Dr. Watt received support for the article research from the National Institutes of Health. The research grant titled Physiologically Based Pharmacokinetic Approach to Determine Dosing on Extracorporeal Life Support (1R01HD097775) was awarded to the University of Utah. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Meropenem is a broad-spectrum carbapenem-type antibiotic commonly used to treat critically ill patients infected with extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. As many of these patients require extracorporeal membrane oxygenation (ECMO) and/or continuous renal replacement therapy (CRRT), it is important to understand how these extracorporeal life support circuits impact meropenem pharmacokinetics. Based on the physicochemical properties of meropenem, it is expected that ECMO circuits will minimally extract meropenem, while CRRT circuits will rapidly clear meropenem. The present study seeks to determine the extraction of meropenem from ex vivo ECMO and CRRT circuits and elucidate the contribution of different ECMO circuit components to extraction., Methods: Standard doses of meropenem were administered to three different configurations (n = 3 per configuration) of blood-primed ex vivo ECMO circuits and serial sampling was conducted over 24 h. Similarly, standard doses of meropenem were administered to CRRT circuits (n = 4) and serial sampling was conducted over 4 h. Meropenem was administered to separate tubes primed with circuit blood to serve as controls to account for drug degradation. Meropenem concentrations were quantified, and percent recovery was calculated for each sample., Results: Meropenem was cleared at a similar rate in ECMO circuits of different configurations (n = 3) and controls (n = 6), with mean (standard deviation) recovery at 24 h of 15.6% (12.9) in Complete circuits, 37.9% (8.3) in Oxygenator circuits, 47.1% (8.2) in Pump circuits, and 20.6% (20.6) in controls. In CRRT circuits (n = 4) meropenem was cleared rapidly compared with controls (n = 6) with a mean recovery at 2 h of 2.36% (1.44) in circuits and 93.0% (7.1) in controls., Conclusion: Meropenem is rapidly cleared by hemodiafiltration during CRRT. There is minimal adsorption of meropenem to ECMO circuit components; however, meropenem undergoes significant degradation and/or plasma metabolism at physiological conditions. These ex vivo findings will advise pharmacists and physicians on the appropriate dosing of meropenem., (© The Author(s), published by EDP Sciences, 2023.)

Background: Ceftazidime and clindamycin are commonly prescribed to critically ill patients who require extracorporeal life support such as ECMO and CRRT. The effect of ECMO and CRRT on the disposition of ceftazidime and clindamycin is currently unknown., Methods: Ceftazidime and clindamycin extraction were studied with ex vivo ECMO and CRRT circuits primed with human blood. The percent recovery of these drugs over time was calculated to determine the degree of interaction between these drugs and circuit components., Results: Neither ceftazidime nor clindamycin exhibited measurable interactions with the ECMO circuit. In contrast, CRRT cleared 100% of ceftazidime from the experimental circuit within the first 2 h. Clearance of clindamycin from the CRRT circuit was slower, with about 20% removed after 6 h., Conclusion: Clindamycin and ceftazidime dosing adjustments are likely required in patients who are supported with CRRT, and future studies to quantify these adjustments should consider the pathophysiology of the patient in combination with the clearance due to CRRT. Dosing adjustments to account for adsorption to ECMO circuit components are likely unnecessary and should focus instead on the pathophysiology of the patient and changes in volume of distribution. These results will help improve the safety and efficacy of ceftazidime and clindamycin in patients requiring ECMO and CRRT., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Thyroid receptor signaling controls major physiological processes and disrupted signaling can cause severe disorders that negatively impact human life. Consequently, methods to detect thyroid receptor ligands are of great toxicologic and pharmacologic importance. Previously, we reported thyroid receptor ligand detection with cell-free protein synthesis of a chimeric fusion protein composed of the human thyroid receptor beta (hTRβ) receptor activator and a β-lactamase reporter. Here, we report a 60% reduction in sensing cost by reengineering the chimeric fusion protein biosensor to include a reporter system composed of either the full-length beta galactosidase (β-gal), the alpha fragment of β-gal (β-gal-α), or a split alpha fragment of the β-gal (split β-gal-α). These biosensor constructs are deployed using E. coli XL1-Blue cell extract to (1) avoid the β-gal background activity abundant in BL21 cell extract and (2) facilitate β-gal complementation reporter activity to detect human thyroid receptor ligands. These results constitute a promising platform for high throughput screening and potentially the portable detection of human thyroid receptor ligands.

Background: Rampage mass shootings (RMS) are a subset of mass shootings occurring in public involving random victims. Due to rarity, RMS are not well-characterized. We aimed to compare RMS and NRMS. We hypothesized that RMS and NRMS would be significantly different with respect to time/season, location, demographics, victim number/fatality rate, victims being law enforcement, and firearm characteristics., Study Design: Mass shootings (4 or more victims shot at a single event) from 2014-2018 were identified in the Gun Violence Archive (GVA). Data were collected from the public domain (e.g. news). Crude comparisons between NRMS and RMS were performed using Chi-squared or Fisher's exact tests. Parametric models of victim and perpetrator characteristics were conducted at the event level using negative binomial regression and logistic regression., Results: There were 46 RMS and 1626 NRMS. RMS occurred most in businesses (43.5%), whereas NRMS occurred most in streets (41.1%), homes (28.6%), and bars (17.9%). RMS were more likely to occur between 6AM-6PM (OR=9.0 (4.8-16.8)). RMS had more victims per incident (23.6 vs. 4.9, RR: 4.8 (4.3,5.4)). Casualties of RMS were more likely to die (29.7% vs. 19.9%, OR: 1.7 (1.5,2.0)). RMS were more likely to have at least one police casualty (30.4% versus 1.8%, OR: 24.1 (11.6,49.9)) or police death (10.9% versus 0.6%, OR: 19.7 (6.4,60.3)). RMS had significantly greater odds that casualties were adult (OR: 1.3 (1.0,1.6)) and female (OR: 1.7 (1.4,2.1)). Deaths in RMS were more likely to be female (OR: 2.0 (1.5,2.5)) and White (OR: 8.6 (6.2,12.0) and less likely to be children (OR: 0.4 (0.2,0.8)). Perpetrators of RMS were more likely to die by suicide (34.8%), be killed by police (28.3%), or be arrested at the scene (26.1%), while more than half of perpetrators from NRMS escaped without death or apprehension (55.8%). Parametric models of perpetrator demographics indicated significant increases in the odds that a RMS shooter was White (OR: 13.9 (7.3,26.6)) or Asian (OR: 16.9 (3.7,78.4)). There was no significant difference in weapon type used (p=0.35)., Conclusion: The demographics, temporality, and location differ between RMS and NRMS, suggesting that they are dissimilar and require different preventive approaches., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2023. Published by Elsevier Ltd.)

Background: ER-Resuscitative Endovascular Balloon Occlusion of the Aorta (ER-REBOA) is an adjunct tool to achieve hemostasis in trauma patients with non-compressible torso hemorrhage. The development of the partial REBOA (pREBOA) allows for distal perfusion of organs while maintaining occlusion of the aorta. The primary aim of this study was to compare rates of acute kidney injury (AKI) in trauma patients who had placement of either a pREBOA or ER-REBOA., Methods: A retrospective chart review of adult trauma patients who underwent REBOA placement between September 2017 and February 2022 was performed. Baseline demographics, information on REBOA placement, and post-procedure complications including AKI, amputations, and mortality were recorded. Chi-squared and T-test analyses were performed with P < .05 considered to be significant., Results: A total of 68 patients met study inclusion criteria with 53 patients (77.9%) having an ER-REBOA. 6.7% of patients treated with pREBOA had a resulting AKI, while 40% of patients treated with ER-REBOA had a resulting AKI, and this difference was significant ( P < .05). The rates of rhabdomyolysis, amputations, and mortality were not significantly different between the two groups., Conclusion: The results from this case series suggest that patients treated with pREBOA have a significantly lower incidence of developing an AKI compared to ER-REBOA. There were no significant differences in rates of mortality, and amputations. Future prospective studies are needed to further characterize the indications and optimal use for pREBOA.

Automobile collisions with driver side intrusion >12 inches or >18 elsewhere meet criteria for trauma activation. However, vehicle safety features have improved since this inception. We hypothesized vehicle intrusion (VI) alone as mechanism-of-injury (MOI) criteria inadequately predicts trauma center activation. A retrospective, single-center chart review of adult patients involved in motor vehicle collisions presenting to a level 1 trauma center from July 2016 to March 2022 was performed. Patients were divided by MOI criteria: VI vs. multiple MOI criteria. 2940 patients met inclusion criteria. The VI group reported lower injury severity scores ( P = 0.004), higher incidence of ED discharge ( P = 0.001), lower ICU admissions ( P = 0.004), and fewer in-hospital procedures ( P = 0.03). Vehicle intrusion was found to have a positive likelihood ratio of 0.889 for predicting trauma center need. According to current guidelines, these results suggest that VI criteria alone may not be an accurate predictor for trauma center transport and require further investigation.

Background: The COVID-19 pandemic has significant impacts on the US socioeconomic structure. Gun violence is a major public health issue and the effects on this area have not been well-elucidated. The objective of this study was to determine the impacts of the pandemic on mass shootings in six major United States cities with historically high rates of gun violence., Methods: Mass shooting data were extracted from an open-source database, Gun Violence Archive. Mass shooting was defined as four or more people shot at a single event. Data from six cities with the highest incidence of mass shootings were analyzed in 2019 versus 2020 (Baltimore, Chicago, Detroit, New Orleans, Philadelphia, and St. Louis). Geographic data were examined to assess changes in each city's mass shooting geographic distribution over time. Quantitative changes were assessed using the Area Deprivation Index (ADI), and qualitative data were assessed using ArcGIS., Results: In 2020, the overall percentage of mass shootings increased by 46.7% though there was no change in the distribution of these events when assessed quantitatively (no change in average ADI) nor qualitatively (using ArcGIS). In the six cities analyzed, the total proportion of mass shooting events was unchanged during the pandemic (21.8% vs 20.6%, p = 0.64). Chicago, the US city with the highest incidence of mass shootings, did not experience a significant change in 2020 (n = 34/91, 37.3% vs. n = 53/126, 42.1%, p = 0.57). Baltimore had a significant decrease in mass shooting events (n = 18/91, 19.8% vs. 10/126, 7.9%, p = 0.01). The other four cities had no significant change in the number of mass shootings (p>0.05)., Conclusion: This study is the first to use ArcGIS technology to describe the patterns of mass shooting in six major US cities during the COVID-19 pandemic. The number of mass shootings in six US cities remained largely unchanged which suggests that changes in mass shootings is likely occurring in smaller cities. Future studies should focus on the changing patterns of homicides in at-risk communities and other possible social influences., Competing Interests: Declaration of Competing Interest AS is a paid consultant for Aroa Biologics. PG is a paid consultant and speaker for Zimmer Biomet and DePuy Synthes. The other authors declare no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Intravenous (IV) fluids are one of the most widely prescribed medications. Despite their frequent usage, IV fluids are often not used appropriately. High-quality evidence to guide the surgeon in the perioperative period is sparse. A plethora of choices for IV fluids exists with limited evidence to help guide the surgeon in specific patient populations and situations. To address this, the authors have set out to provide a critical review of commonly used IV fluids to treat surgical patients. Gaps in the existing literature for the surgical population will also be discussed as potential target areas for future research.

Cell-free protein synthesis (CFPS) is a versatile biotechnology platform enabling a broad range of applications including clinical diagnostics, large-scale production of officinal therapeutics, small-scale on-demand production of personal magistral therapeutics, and exploratory research. The shelf stability and scalability of CFPS systems also have the potential to overcome cost and infrastructure challenges for distributing and using essential medical tests at home in both high- and low-income countries. However, CFPS systems are often more time-consuming and expensive to prepare than traditional in vivo systems, limiting their broader use. Much work has been done to lower CFPS costs by optimizing cell extract preparation, small molecule reagent recipes, and DNA template preparation. In order to further reduce reagent cost and preparation time, this work presents a CFPS system that does not require separately purified DNA template. Instead, a DNA plasmid encoding the recombinant protein is transformed into the cells used to make the extract, and the extract preparation process is modified to allow enough DNA to withstand homogenization-induced shearing. The finished extract contains sufficient levels of intact DNA plasmid for the CFPS system to operate. For a 10 mL scale CFPS system expressing recombinant sfGFP protein for a biosensor, this new system reduces reagent cost by more than half. This system is applied to a proof-of-concept glutamine sensor compatible with smartphone quantification to demonstrate its viability for further cost reduction and use in low-resource settings., (© 2023 American Institute of Chemical Engineers.)

Introduction: Continuous prediction surveillance modeling is an emerging tool giving dynamic insight into conditions with potential mitigation of adverse events (AEs) and failure to rescue. The Epic electronic medical record contains a Deterioration Index (DI) algorithm that generates a prediction score every 15 min using objective data. Previous validation studies show rapid increases in DI score (≥14) predict a worse prognosis. The aim of this study was to demonstrate the utility of DI scores in the trauma intensive care unit (ICU) population., Methods: A prospective, single-center study of trauma ICU patients in a Level 1 trauma center was conducted during a 3-mo period. Charts were reviewed every 24 h for minimum and maximum DI score, largest score change (Δ), and AE. Patients were grouped as low risk (ΔDI <14) or high risk (ΔDI ≥14)., Results: A total of 224 patients were evaluated. High-risk patients were more likely to experience AEs (69.0% versus 47.6%, P = 0.002). No patients with DI scores <30 were readmitted to the ICU after being stepped down to the floor. Patients that were readmitted and subsequently died all had DI scores of ≥60 when first stepped down from the ICU., Conclusions: This study demonstrates DI scores predict decompensation risk in the surgical ICU population, which may otherwise go unnoticed in real time. This can identify patients at risk of AE when transferred to the floor. Using the DI model could alert providers to increase surveillance in high-risk patients to mitigate unplanned returns to the ICU and failure to rescue., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We describe an experimental campaign that replicated the performance assessment of logic gates engineered into cells of Saccharomyces cerevisiae by Gander et al. Our experimental campaign used a novel high-throughput experimentation framework developed under Defense Advanced Research Projects Agency's Synergistic Discovery and Design program: a remote robotic lab at Strateos executed a parameterized experimental protocol. Using this protocol and robotic execution, we generated two orders of magnitude more flow cytometry data than the original experiments. We discuss our results, which largely, but not completely, agree with the original report and make some remarks about lessons learned. Graphical Abstract ., (© The Author(s) 2022. Published by Oxford University Press.)

Background: Combat applications of tourniquets for extremity trauma have led to increased civilian prehospital tourniquet use. Studies have demonstrated that appropriate prehospital tourniquet application can decrease the incidence of arrival in shock without increasing limb complications. The aim of this study was to examine outcomes of prehospital tourniquet placement without definitive vascular injury., Methods: Retrospective review was performed of a prospectively maintained database by the American Association for the Surgery of Trauma from 29 trauma centers. Patients in this subset analysis did not have a significant vascular injury as determined by imaging or intra-operatively. Patients who received prehospital tourniquets (PHTQ) were compared to patients without prehospital tourniquets (No-PHTQ). Outcomes were amputation rates, nerve palsy, compartment syndrome, and in-hospital mortality., Results: A total of 622 patients had no major vascular injury. The incidence of patients without major vascular injury was higher in the PHTQ group (n = 585/962, 60.8 vs n = 37/88, 42.0%, P < .001). Cohorts were similar in age, gender, penetrating mechanism, injury severity scores (ISS), abbreviated injury score (AIS), and mortality ( P > .05). Amputation rates were 8.3% (n = 49/585) in the PHTQ group compared to 0% (n = 0/37) in the No-PHTQ group. Amputation rates were higher in PHTQ than No-PHTQ with similar ISS and AIS ( P = .96, P = .59). The incidence of nerve palsy and compartment syndrome was not different ( P > .05)., Conclusions: This study showed a significant amount of prehospital tourniquets are being placed on patients without vascular injuries. Further studies are needed to elucidate the appropriateness of prehospital tourniquets, including targeted education of tourniquet placement.

Purpose: The COVID-19 pandemic has disrupted many facets of life. We evaluated pandemic-related health care experiences, COVID-19 prevention behaviors and measures, health behaviors, and psychosocial outcomes among rural and urban cancer patients., Methods: Among 1,472 adult cancer patients, who visited Huntsman Cancer Institute in the past 4 years and completed a COVID-19 survey (August-September 2020), we assessed the impact of the pandemic on medical appointments, prevention/health behaviors, and psychosocial factors, stratified by urbanicity., Findings: Mean age was 61 years, with 52% female, 97% non-Hispanic White, and 27% were residing in rural areas. Rural versus urban patients were more likely to be older, not employed, uninsured, former/current smokers, consume alcohol, and have pandemic-related changes/cancellations in surgery appointments (all P<.05). Changes/cancellations in other health care access (eg, doctor's visits) were also common, particularly among urban patients. Urban versus rural patients were more likely to socially distance, use masks and hand sanitizer, and experience changes in exercise habits and in their daily lives (all P<.05). Less social interaction and financial stress were common among cancer patients but did not differ by urbanicity., Conclusions: These findings suggest that the COVID-19 pandemic had a substantial impact on cancer patients, with several challenges specific to rural patients. This comprehensive study provides unique insights into the first 6 months of COVID-19 pandemic-related experiences and continuity of care among rural and urban cancer patients predominantly from Utah. Further research is needed to better characterize the pandemic's short- and long-term effects on rural and urban cancer patients and appropriate interventions., (© 2022 National Rural Health Association.)

Introduction: Venous thromboembolism (VTE) contributes to significant morbidity in trauma patients while increasing hospital costs and length of stay. Standard trauma prophylaxis dosing with enoxaparin 30 mg twice daily may be inadequate to prevent VTEs. The objective of this study was to compare standard dosing of enoxaparin to an increased dose of enoxaparin 40 mg twice daily for trauma patients. We hypothesized that increasing thromboprophylaxis dosing leads to an increase in therapeutic anti-Xa levels and reduced VTE rates., Methods: A retrospective study was performed from January 2020 to June 2021 at a Level I trauma center, following implementation of an increased enoxaparin dosing strategy. Patients with increased enoxaparin dosing were compared with those who received standard dosing. The primary outcome evaluated was the incidence of subtherapeutic anti-Xa levels. Secondary outcomes evaluated VTE rates and clinically significant bleed., Results: A total of 204 trauma patients were identified. Ninety-one patients received an increased enoxaparin dose compared to 113 who received standard dosing. The baseline demographics of both groups were similar ( P > .05). Subtherapeutic levels were higher with standard dosing compared to the increased dose (50 vs 22%, P = .003). Higher VTE rates were observed with standard dosing compared to higher dosing (6.2 vs 3.3%) but with a lower incidence of major bleed (1.8 vs 4.4%). Overall annual VTE rates decreased from 1.6 to 1.3% after implementation of the increased dosing regimen., Conclusions: This study demonstrated that an increased dosing strategy decreased rates of subtherapeutic anti-Xa levels and trended toward lower overall VTE rates in trauma.

Differentiated thyroid carcinomas is associated with an excellent prognosis. The treatment of choice for differentiated thyroid carcinoma is surgery, followed by radioactive iodine ablation (iodine-131) in select patients and thyroxine therapy in most patients. Surgery is also the main treatment for medullary thyroid carcinoma, and kinase inhibitors may be appropriate for select patients with recurrent or persistent disease that is not resectable. Anaplastic thyroid carcinoma is almost uniformly lethal, and iodine-131 imaging and radioactive iodine cannot be used. When systemic therapy is indicated, targeted therapy options are preferred. This article describes NCCN recommendations regarding management of medullary thyroid carcinoma and anaplastic thyroid carcinoma, and surgical management of differentiated thyroid carcinoma (papillary, follicular, Hürthle cell carcinoma).