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A variety of equations are used to estimate glomerular filtration rate (eGFR). These formulas have never been validated in the setting of traumatic amputation. In this retrospective study involving 255 military personnel with traumatic amputations at a single outpatient center, muscle mass lost was estimated using percentage of estimated body weight lost (% EBWL). Serum creatinine (Scr) and eGFR by the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations were compared to % EBWL for each patient. The average Scr for the group studied was also compared with a cohort matched for age, sex, and race from the Third National Health and Nutrition Examination Survey (NHANES III). Percentage EBWL correlated significantly with Scr (R2 = 0.095, p < 0.0001), eGFR by MDRD (R2 = 0.077, p < 0.0001), and eGFR by CKD-EPI (R2 = 0.074, p < 0.0001). The average Scr was significantly lower than a similar population from NHANES III (0.83 +/- 0.137 mg/dL vs. 1.14 +/- 0.127 mg/dL, p < 0.0001). Percentage EBWL has a significant correlation with Scr and eGFR by both the MDRD and CKD-EPI equations. Furthermore, patients with traumatic amputation have significantly lower Scr values than the general population. Creatinine-based estimators of GFR may overestimate renal function in the setting of traumatic amputation. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury (TBI) is associated with a variety of adverse long-term outcomes and increases sympathetic nervous system activation, which could increase the risk of arrhythmias including atrial fibrillation or atrial flutter (AF/AFL)., Objective: We examined episodes of TBI and subsequent AF/AFL in a large cohort of post-9/11 servicemembers and veterans., Methods: The variable of interest was TBI, stratified by severity (mild, moderate/severe, and penetrating). The outcome was a subsequent diagnosis of AF/AFL. We used Fine-Gray competing risks models to evaluate the potential risk imparted by TBI on subsequent AF/AFL., Results: Of the 1,924,900 participants included in the analysis, 369,891 (19.2%) experienced an episode of documented TBI. Most were young (63% <35 years), male (81.7%), and non-Hispanic White (62.7%). AF/AFL was diagnosed in 22,087 patients. On univariate analysis, only penetrating TBI (hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.84-2.23; P < .001) was associated with AF/AFL compared with veterans without TBI. After adjustment in the full multivariable model (adjusted for age, sex, race and ethnicity, service branch, rank, component, and comorbidities), mild (HR 1.27, 95% CI 1.22-1.32; P < .001), moderate/severe (HR, 1.34; 95% CI, 1.24-1.44; P < .001), and penetrating TBI (HR, 1.82; 95% CI, 1.65-2.02; P < .001) were significantly associated with AF/AFL compared with no TBI. Post hoc analyses demonstrated that the risk of AF/AFL was concentrated in female and younger patients., Conclusion: We found that an episode of TBI, particularly penetrating TBI, significantly increased the risk for AF/AFL. Further work is needed to delineate the long-term risk of arrhythmias after TBI., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Published by Elsevier Inc.)

Objective: We investigated the potential of acute canagliflozin administration to mitigate acute kidney injury (AKI) and attenuate deleterious pro-inflammatory cytokine release in a clinically relevant swine model of severe renal ischemia reperfusion injury (IRI) induced by hemorrhage and aortic occlusion., Background: Long-term canagliflozin use attenuates renal function decline and reduces AKI in diabetes mellitus and heart failure patients. Whilst several reports indicate prophylactic SGLT2 inhibition prevents AKI in IRI, the efficacy of acute administration on IRI and inflammation is not known., Methods: Female swine (n=16) underwent controlled hemorrhage of 25% blood volume, followed by 90 min of aortic occlusion at the level of the renal ostia (via Resuscitative Endovascular Balloon Occlusion of the Aorta). A single 300 mg dose of oral canagliflozin or vehicle (saline) was delivered 5 mins into aortic occlusion. Hemodynamic monitoring, markers of renal function (serum creatinine, blood urea nitrogen, proteinuria and urinary neutrophil gelatinase-associated lipocalin) and serum cytokine concentrations (including interleukins: IL-1RA, IL-6, IL-8, IL-10, IL-18; and Tumor necrosis factor alpha) were analyzed after IRI, and during a 6h critical care phase., Results: Compared to controls, animals receiving canagliflozin had less severe AKI, improved creatinine clearance, reduced proteinuria, and significantly lower tubular damage as evidenced by histopathology and urinary NGAL. Furthermore, the pro-inflammatory cytokine IL-6 was markedly attenuated without reduction in anti-inflammatory cytokines (IL-1RA and IL-10)., Conclusions: A single dose of canagliflozin administered shortly into ischemic insult mitigates AKI and attenuates harmful pro-inflammatory cytokine release following trauma or surgery. These findings suggest a potential novel therapeutic role for canagliflozin in mitigating the effects of renal IRI worthy of further investigation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Disease and non-battle injury (DNBI) has historically been the leading casualty type among service members in warfare and a leading health problem confronting military personnel, resulting in significant loss of manpower. Studies show a significant increase in disease burden for DNBI when compared to combat-related injuries. Understanding the causes of and trends in DNBI may help guide efforts to develop preventive measures and help increase medical readiness and resiliency. However, despite its significant disease burden within the military population, DNBI remains less studied than battle injury. In this review, we aimed to evaluate the recently published literature on DNBI and to describe the characteristics of these recently published studies., Materials and Methods: This systematic review is reported in the Prospective Register of Systematic Reviews database. The systematic search for published articles was conducted through July 21, 2022, in Cumulative Index of Nursing and Allied Health, Cochrane Library, Defense Technical Information Center, Embase, and PubMed. Guided by the Preferred Reporting Items for Systematic Reviews and Meta-analyses, the investigators independently screened the reference lists on the Covidence website (covidence.org). An article was excluded if it met any of the following criteria: (1) Published not in English; (2) published before 2010; (3) data used before 2001; (4) case reports, commentaries, and editorial letters; (5) systematic reviews or narrative reviews; (6) used animal models; (7) mechanical or biomechanical studies; (8) outcome was combat injury or non-specified; (9) sample was veterans, DoD civilians, contractors, local nationals, foreign military, and others; (10) sample was U.S. Military academy; (11) sample was non-deployed; (12) bioterrorism study; (13) qualitative study. The full-text review of 2 independent investigators reached 96% overall agreement (166 of 173 articles; κ = 0.89). Disagreements were resolved by a third reviewer. Study characteristics and outcomes were extracted from each article. Risk of bias was assessed using the Newcastle-Ottawa Scale. Meta-analysis of pooled estimates of incidence rates for disease (D), non-battle injury (NBI), and combined DNBI was created using random-effects models., Results: Of the 3,401 articles, 173 were included for the full review and 29 (16.8%) met all inclusion criteria. Of the 29 studies included, 21 (72.4%) were retrospective designs, 5 (17.2%) were prospective designs, and 3 (10.3%) were surveys. Across all studies, the median number of total cases reported was 1,626 (interquartile range: 619.5-10,203). The results of meta-analyses for 8 studies with reported incidence rates (per 1,000 person-years) for D (n = 3), NBI (n = 7), and DNBI (n = 5) showed pooled incidence rates of 22.18 per 1,000 person-years for D, 19.86 per 1,000 person-years for NBI, and 50.97 per 1,000 person-years for combined DNBI. Among 3 studies with incidence rates for D, NBI, and battle injury, the incidence rates were 20.32 per 1,000 person-years for D, 6.88 per 1,000 person-years for NBI, and 6.83 per 1,000 person-years for battle injury., Conclusions: DNBI remains the leading cause of morbidity in conflicts involving the U.S. Military over the last 20 years. More research with stronger designs and consistent measurement is needed to improve medical readiness and maintain force lethality., Level of Evidence: Systematic Review and Meta-Analysis, Level III., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

PURIFY-OBS-1 is an observational study evaluating the safety and efficacy of Seraph 100 ® Microbind Affinity Blood Filter (Seraph 100) use for COVID-19 patients with respiratory failure admitted to the intensive care unit (ICU). The Seraph 100 is a hemoperfusion device containing heparin-coated beads that can bind to, and reduce levels of, some circulating pathogens and inflammatory molecules. This study evaluated whether treatment with the Seraph 100 affected circulating and mucosal antibody levels in critically ill COVID-19 subjects. SARS-CoV-2 anti-spike and anti-nucleocapsid IgG and IgA levels in serum were evaluated at enrollment and on days 1, 4, 7, and 28 after Seraph 100 application, while anti-spike and nucleocapsid IgG, IgA, and secretory IgA levels in tracheal aspirates were evaluated at enrollment and on days 1, 2, 3, 7, and 28. Serum samples were also collected from the pre- and post-filter lines at 1 and 4 h following Seraph 100 application to evaluate the direct impact of the filter on circulating antibody levels. Treatment with the Seraph 100 did not alter the levels of circulating or mucosal antibodies in critically ill COVID-19 subjects admitted to the ICU.

The endothelial glycocalyx, a gel-like layer that lines the luminal surface of blood vessels, is composed of proteoglycans, glycoproteins, and glycosaminoglycans. The endothelial glycocalyx plays an essential role in vascular homeostasis, and its degradation in trauma and sepsis can lead to microvascular dysfunction and organ injury. While there are no proven therapies for preventing or treating endothelial glycocalyx degradation, some initial literature suggests that plasma may have a therapeutic role in trauma and sepsis patients. Overall, the literature suggesting the use of plasma as a therapy for endothelial glycocalyx degradation is non-clinical basic science or exploratory. Plasma is an established therapy in the resuscitation of patients with hemorrhage for restoration of coagulation factors. However, plasma also contains other bioactive components, including sphingosine-1 phosphate, antithrombin, and adiponectin, which may protect and restore the endothelial glycocalyx, thereby helping to maintain or restore vascular homeostasis. This narrative review begins by describing the endothelial glycocalyx in health and disease: we discuss the overlapping disease mechanisms in trauma and sepsis that lead to its damage and introduce plasma transfusion as a potential therapy for prevention and treatment of endothelial glycocalyx degradation. Second, we review the literature on plasma as an exploratory therapy for endothelial glycocalyx degradation in trauma and sepsis. Third, we discuss the safety of plasma transfusion by reviewing the adverse events associated with plasma and other blood product transfusions, and we examine modern transfusion precautions that have enhanced the safety of plasma transfusion. We conclude that the literature proposes that plasma may have the potential to prevent and treat endothelial glycocalyx degradation in trauma and sepsis, indicating the need for further research., (© 2024. The Author(s).)

Introduction: United States Military operations in resource limited areas are increasing. Furthermore, future peer or near-peer conflicts will require caring for larger numbers of casualties with limited resources. In this setting, traditional renal replacement therapy is not feasible and novel methods are required to address severe acute kidney injury in austere environments lacking definitive therapies. Here, we describe experiments designed to determine the efficacy of a novel peritoneal packing material (Potassium Binding Pack-PBP, CytoSorbents INC) for the acute management of severe hyperkalemia., Materials and Methods: Male swine (52 ±1 kg) were nephrectomized via midline laparotomy under a plane of anesthesia and randomized into one of two experimental groups (PBP & CON). Exogenous potassium was infused to achieve a serum potassium level of 7.5 mEq/L. Novel potassium absorbing packs (PBP) or sham packs (CON) were placed in the right and left upper quadrants, and the right and left paracolic gutters of the abdomen to simulate four-quadrant packing (n = 6, n = 5, respectively). Two liters of peritoneal dialysis fluid was instilled into the abdomen and temporary closure performed. Animals were observed for 12 hours. Serum and peritoneal fluid (dialysate) potassium levels were sampled at T = 15, 30, 60 min, and Q60min thereafter. Animals were humanely euthanized at the end of the observation period., Results: Baseline characteristics were similar between groups. Pairwise analysis showed that serum potassium concentrations were significantly lower in the PBP group compared to CON at T = 540 and T = 720 (P = 0.006 and P = 0.015, respectively). Potassium concentrations were significantly lower in dialysate of the PBP group compared to CON at all time points after T = 15 (T = 30, P = 0.017; T = 60 through T = 720, P < 0.001)., Conclusions: This is the first demonstration of an effective technology for the management of hyperkalemia in trauma in the absence of standard of care; renal replacement therapy. We identified that PBP was able to consistently maintain a concentration gradient between dialysate in the peritoneum and system potassium concentration throughout the experiment. Furthermore, systemic potassium concentrations were reduced in a clinically relevant manner in the PBP group compared to CON. This suggests that peritoneal packing technology for the management of metabolic disturbances in trauma has potential for clinical application. These results are preliminary and should be interpreted with caution., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aggregate statistics can provide intra-conflict and inter-conflict mortality comparisons and trends within and between U.S. combat operations. However, capturing individual-level data to evaluate medical and non-medical factors that influence combat casualty mortality has historically proven difficult. The Department of Defense (DoD) Trauma Registry, developed as an integral component of the Joint Trauma System during recent conflicts in Afghanistan and Iraq, has amassed individual-level data that have afforded greater opportunity for a variety of analyses and comparisons. Although aggregate statistics are easily calculated and commonly used across the DoD, other issues that require consideration include the impact of individual medical interventions, non-medical factors, non-battle-injured casualties, and incomplete or missing medical data, especially for prehospital care and forward surgical team care. Needed are novel methods to address these issues in order to provide a clearer interpretation of aggregate statistics and to highlight solutions that will ultimately increase survival and eliminate preventable death on the battlefield. Although many U.S. military combat fatalities sustain injuries deemed non-survivable, survival among these casualties might be improved using primary and secondary prevention strategies that prevent injury or reduce injury severity. The current commentary proposes adjustments to traditional aggregate combat casualty care statistics by integrating statistics from the DoD Military Trauma Mortality Review process as conducted by the Joint Trauma System and Armed Forces Medical Examiner System., (2024.)

Introduction: The extent of racial/ethnic disparities and whether they are attenuated in the Veteran population compared to the total US population is not well understood. We aimed to assess racial/ethnic mortality disparities from all-cause, cardiovascular (CVD) and cancer among post-9/11 military Veterans with and without exposure to TBI, compared to the total US population., Methods: This cohort study included 2,502,101 US military Veterans (18,932,083 person-years) who served after 09/11/2001 with 3 or more years of care in the Military Health System (MHS); or had 3 or more years of care in the MHS and 2 or more years of care in the Veterans Health Administration. Mortality follow-up occurred from 01/01/2002 to 12/31/2020. Mortality rate ratios (MRR) from negative binomial regression models were reported for racial/ethnic groups compared to White non-Hispanic Veterans for all-cause, CVD and cancer mortality. Veteran MRR were compared to the total US population., Results: Mortality rates for Black Non-Hispanic Veterans were higher for all-cause (MRR = 1.21;95%CI: 1.13-1.29; p < 0.001), CVD (MRR = 1.78;95%CI: 1.62-1.96; p < 0.001) and cancer (MRR = 1.17;95%CI: 1.10-1.25; p < 0.001) than in White Non-Hispanic Veterans. Among Veterans with TBI, only Black Non-Hispanics had higher mortality than White Non-Hispanics and only for CVD (MRR = 1.32;95%CI: 1.12-1.54; p < 0.001), while CVD mortality was higher among Veterans without TBI (MRR = 1.77;95%CI: 1.63-1.93;p < 0.001). MRR for Black Non-Hispanics in the total US population, were consistently higher than those in the Veteran population for all-cause (MRR = 1.52;95%CI: 1.46-1.58; p < 0.001), CVD (MRR = 2.03;95%CI: 1.95-2.13; p < 0.001) and cancer (MRR = 1.26;95%CI: 1.22-1.30; p < 0.001)., Conclusion: This Veteran cohort experienced less racial/ethnic disparity in mortality than the total US population, especially among Veterans with TBI., (© 2024. W. Montague Cobb-NMA Health Institute.)

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is used to control noncompressible hemorrhage not addressed with traditional tourniquets. However, REBOA is associated with acute kidney injury (AKI) and subsequent mortality in severely injured trauma patients. Here, we investigated how the degree of aortic occlusion altered the extent of AKI in a porcine model. Female Yorkshire-cross swine ( n = 16, 68.1 ± 0.7 kg) were anesthetized and had carotid and bilateral femoral arteries accessed for REBOA insertion and distal and proximal blood pressure monitoring. Through a laparotomy, a 6-cm liver laceration was performed and balloon inflation was performed in zone 1 of the aorta for 90 min, during which animals were randomized to target distal mean arterial pressures of 25 or 45 mmHg via balloon volume adjustment. Blood draws were taken at baseline, end of occlusion, and time of death, at which point renal tissues were harvested 6 h after balloon deflation for histological and molecular analyses. Renal blood flow was lower in the 25-mmHg group (48.5 ± 18.3 mL/min) than in the 45-mmHg group (177.9 ± 27.2 mL/min) during the occlusion phase, which recovered and was not different after balloon deflation. AKI was more severe in the 25-mmHg group, as evidenced by circulating creatinine, blood urea nitrogen, and urinary neutrophil gelatinase-associated lipocalin. The 25-mmHg group had increased tubular necrosis, lower renal citrate synthase activity, increased tissue and circulating syndecan-1, and elevated systemic inflammatory cytokines. The extent of renal ischemia-induced AKI is associated with the magnitude of mitochondrial biomass and systemic inflammation, highlighting potential mechanistic targets to combine with partial REBOA strategies to prevent AKI. NEW & NOTEWORTHY Large animal models of ischemia-reperfusion acute kidney injury (IR-AKI) are lacking. This report establishes a titratable IR-AKI model in swine in which a balloon catheter can be used to alter distal pressures experienced by the kidney, thus controlling renal blood flow. Lower blood flow results in greater renal dysfunction and structural damage, as well as lower mitochondrial biomass, elevated systemic inflammation, and vascular dysfunction.

Sickle cell nephropathy (SCN) is a leading cause of morbidity and mortality in sickle cell disease (SCD). Early intervention is crucial for mitigating its effects. However, current diagnostic methods rely on generic tests and may not detect SCN until irreversible renal damage occurs. Therefore, specific biomarkers for early diagnosis of SCN are needed. Urinary exosomes, membrane-bound vesicles secreted by renal podocytes and epithelial cells, contain both common and cell type-specific membrane and cytosolic proteins, reflecting the physiologic and pathophysiologic states of the kidney. Using proteomics, we analyzed the proteomes of urinary exosomes from humanized SCD mice at 2 months (without albuminuria) and 4 months (with albuminuria) of age. Excretion of 164 proteins were significantly increased and 176 proteins was significantly decreased in the exosomes when mice developed albuminuria. Based on the relevance to SCD, chronic kidney disease and Western blot confirmation in mice, we analyzed protein abundance of heparanase, cathepsin C, α2-macroglobulin and sarcoplasmic endoplasmic Ca 2+ ATPase-3 (SERCA3) in the urinary exosomes and urine of 18 SCD subjects without albuminuria and 12 subjects with albuminuria using Western blot analyses. Both male and female subjects increased or tended to increase the excretion of these proteins in their urinary exosomes upon developing albuminuria, but female subjects demonstrated stronger correlations between the excretion of these proteins and urine albumin creatinine ratio (UACR) compared to male subjects. In contrast, exosomal excretion of Tamm-Horsfall protein, β-actin and SHP-1 was independent of albuminuria. These findings provide a foundation for a time-course study to determine whether increases in the levels of these proteins precede the onset of albuminuria in patients, which will help determine the potential of these proteins as biomarkers for early detection of SCN., Competing Interests: 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Packialakshmi, Limerick, Ackerman, Lin, Nekhai, Oliver, Stewart, Knepper, Fitzhugh and Zhou.)

Importance: While brain cancer is rare, it has a very poor prognosis and few established risk factors. To date, epidemiologic work examining the potential association of traumatic brain injury (TBI) with the subsequent risk of brain cancer is conflicting. Further data may be useful., Objective: To examine whether a history of TBI exposure is associated with the subsequent development of brain cancer., Design, Setting, and Participants: A retrospective cohort study was conducted from October 1, 2004, to September 20, 2019, and data analysis was performed between January 1 and June 26, 2023. The median follow-up for the cohort was 7.2 (IQR, 4.1-10.1) years. Veterans Affairs (VA) and Department of Defense (DoD) administrative data on 1 919 740 veterans from the Long-Term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium were included., Exposure: The main exposure of interest was TBI severity (categorized as mild, moderate or severe [moderate/severe], and penetrating)., Main Outcomes and Measures: The outcome of interest was the development of brain cancer based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic codes in either the DoD/VA medical records or from the National Death Index., Results: After 611 107 exclusions (predominately for no encounter during the study period), a cohort including 1 919 740 veterans was included, most of whom were male (80.25%) and non-Hispanic White (63.11%). Median age at index date was 31 (IQR, 25-42) years. The cohort included 449 880 individuals with TBI (mild, 385 848; moderate/severe, 46 859; and penetrating, 17 173). Brain cancer occurred in 318 individuals without TBI (0.02%), 80 with mild TBI (0.02%), 17 with moderate/severe TBI (0.04%), and 10 or fewer with penetrating TBI (≤0.06%). After adjustment, moderate/severe TBI (adjusted hazard ratio [AHR], 1.90; 95% CI, 1.16-3.12) and penetrating TBI (AHR, 3.33; 95% CI, 1.71-6.49), but not mild TBI (AHR, 1.14; 95% CI, 0.88-1.47), were associated with the subsequent development of brain cancer., Conclusions and Relevance: In this cohort study of veterans of the Iraq and Afghanistan wars, moderate/severe TBI and penetrating TBI, but not mild TBI, were associated with the subsequent development of brain cancer.

Glioblastoma multiforme (GBM) is an aggressive variant of central nervous system gliomas that carries a dismal prognosis. Although GBM is the most frequently occurring and malignant type of glioma accounting for more than 60% of all brain tumors in adults, its overall incidence is rare, occurring at a rate of 3.21 per 100,000 persons. Little is known about the etiology of GBM, but one proposed theory is that GBM pathogenesis may be linked to a chronic inflammatory course initiated by traumatic injury to the brain. Limited case reports have suggested an association between GBMs and traumatic brain injury (TBI), but larger case-control and epidemiologic studies have been inconclusive. We present three service members (two active duty and one retired) who developed GBM near the original site of prior head trauma. Each service member's military occupation was in the special operations community and shared a common theme of TBI following head trauma/injury. The current research on the association between TBI and GBM is limited and conflicting, predominantly due to the low incidence of the disease in the general population. Evidence has indicated that TBI should be considered a chronic disease with long-term health impacts, including long-term disability, dementia, epilepsy, mental health conditions, and cardiovascular diseases. With the addition of our patients, as well as a recently published study proposing a molecular association between trauma and GBM, further research is needed to better understand the potential relationship., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Introduction: Novel hemoperfusion systems are emerging for the treatment of sepsis. These devices can directly remove pathogens, pathogen-associated molecular patterns, cytokines, and other inflammatory markers from circulation. However, significant safety concerns such as potential antibiotic clearance need to be addressed prior to these devices being used in large clinical studies., Methods: Prospective, observational study of 34 participants undergoing treatment with the Seraph 100® Microbind Affinity Blood Filter (Seraph 100) device at 6 participating sites in the USA. Patients were included for analysis if they had a record of receiving an antibiotic concurrent with Seraph 100 treatment. Patients were excluded if there was missing information for blood flow rate. Blood samples were drawn pre- and post-filter at 1 h and 4 h after treatment initiation. These average pre- and post-filter time-concentration observations were then used to estimate antibiotic clearance in L/h (CLSeraph) due to the Seraph 100 device., Results: Of the 34 participants in the study, 17 met inclusion and exclusion criteria for the antibiotic analysis. Data were obtained for 7 antibiotics (azithromycin, cefazolin, cefepime, ceftriaxone, linezolid, piperacillin, and vancomycin) and one beta-lactamase inhibitor. Mean CLSeraph for the antibiotics investigated ranged from -0.57 to 0.47 L/h. No antibiotic had a CLSeraph statistically significant from 0., Discussion/conclusion: The Seraph 100 did not significantly clear any measured antibiotic in clinical samples. These data give further evidence to suggest that these therapies may be safely administered to critically ill patients and will not impact concentrations of administered antibiotics., (© 2024 S. Karger AG, Basel.)

Background: Patients with kidney failure are at risk for lethal complications from hyperkalemia. Resuscitation, medications, and hemodialysis are used to mitigate increased potassium (K + ) levels in circulating blood; however, these approaches may not always be readily available or effective, especially in a resource limited environment. We tested a sorbent cartridge (KC, K + ontrol CytoSorbents Medical Inc., Monmouth Junction, New Jersey) which contains a resin adsorber for K + . The objective of this study was to test the utility of KC in an ex vivo circulation system. We hypothesized that KC reduces K + levels in extracorporeal circulation of donor swine whole blood infused with KCl., Methods: A six-hour circulation study was carried out using KC, a NxStage (NxStage Medical, Inc., Lawrence, MA) membrane, blood bag containing heparinized whole blood with KCl infusion, 3/16-inch ID tubing, a peristaltic pump, and flow sensors. The NxStage permeate line was connected back to the main circuit in the Control group ( n = 6), creating a recirculation loop. For KC group ( n = 6), KC was added to the recirculation loop, and a continuous infusion of KCl at 10 mEq/hour was administered for two hours. Blood samples were acquired at baseline and every hour for 6 h., Results: In the control group, K + levels remained at ∼9 mmol/L; 9.1 ± 0.4 mmol/L at 6 h. In the KC group, significant decreases in K + at hour 1 (4.3 ± 0.3 mmol/L) and were sustained for the experiment duration equilibrating at 4.6 ± 0.4 mmol/L after 6 h ( p = 0.042). Main loop blood flow was maintained under 400 mL/min; recirculation loop flow varied between 60 and 70 mL/min in the control group and 45-55 mL/min in the KC group. Decreases in recirculation loop flow in KC group required 7% increase of pump RPM., Conclusions: During ex-vivo extracorporeal circulation using donor swine blood, KC removed approximately 50% of K + , normalizing circulating levels., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: T.D.G., M.G., T.K., T.G., P.P.C. are employed by CytoSorbents Corporation and receive salary and stock compensation.

Hemorrhage is a leading cause of death in trauma. Tourniquets are effective at controlling extremity hemorrhage and have saved lives. However, tourniquets can cause ischemia reperfusion injury of limbs, leading to systemic inflammation and other adverse effects, which results in secondary damage to the kidney, lung, and liver. A clinically relevant animal model is critical to understanding the pathophysiology of this process and developing therapeutic interventions. Despite the importance of animal models, tourniquet-induced lower limb ischemia/reperfusion (TILLIR) models to date lack a hemorrhage component. We sought to develop a new TILLIR model that included hemorrhage and analyze the subsequent impact on kidney, lung and liver injuries. Four groups of mice were examined: group 1) control, group 2) hemorrhage, group 3) tourniquet application, and group 4) hemorrhage and tourniquet application. The hemorrhagic injury consisted of the removal of 15% of blood volume through the submandibular vein. The tourniquet injury consisted of orthodontic rubber bands applied to the inguinal area bilaterally for 80 min. Mice were then placed in metabolic cages individually for 22 h to collect urine. Hemorrhage alone did not significantly affect transcutaneous glomerular filtration rate (tGFR), blood urea nitrogen (BUN) or urinary kidney injury molecule-1 (KIM-1) levels. Without hemorrhage, TILLIR decreased tGFR by 46%, increased BUN by 162%, and increased KIM-1 by 27% ( p < 0.05 for all). With hemorrhage, TILLIR decreased the tGFR by 72%, increased BUN by 395%, and increased urinary KIM-1 by 37% ( p < 0.05 for all). These differences were statistically significant ( p < 0.05). While hemorrhage had no significant effect on TILLIR-induced renal tubular degeneration and necrosis, it significantly increased TILLIR-induced lung total injury scores and congestion, and fatty liver. In conclusion, hemorrhage exacerbates TILLIR-induced acute kidney injury and structural damage in the lung and liver., Competing Interests: 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 Packialakshmi, Burmeister, Anderson, Morgan, Cannon, Kiang, Feng, Lee, Stewart and Zhou.)

Health behaviors may be core contributors to cognition and mental health following mild traumatic brain injury (TBI). The aims of the present study examined: (1) whether health behaviors including sleep duration, alcohol use, and physical activity differed in injured military personnel with and without deployment-related mild TBI history and (2) the relative contributions of health behaviors and deployment-related mild TBI history to self-reported cognitive, posttraumatic stress disorder (PTSD), and depressive symptoms. Participants included 3076 military personnel injured on deployment participating in the Wounded Warrior Recovery Project, an ongoing web-based study. Military personnel with deployment-related mild TBI history reported similar rates of physical activity and levels of alcohol problems as those without, but were less likely to report receiving the recommended duration of sleep. When adjusting for demographic and injury variables, all three health behaviors were associated with cognitive, PTSD, and depressive symptoms. Alcohol problems demonstrated significant but small effects across all outcomes measures (η p 2 =.01) whereas physical activity was associated with slightly larger effects albeit still within the small range (η p 2 =.02-0.04). Duration of sleep bordered a medium effect for cognitive symptoms (η p 2 =.05) and was in the medium range for PTSD and depressive symptoms (η p 2 =.06). Although deployment-related mild TBI history was significant in all models, effect sizes were small (η p 2 =.01). Findings from the present study provide support that health behaviors have stronger effects with regard to cognitive, PTSD, and depressive symptoms compared to deployment-related mild TBI history in military personnel and, given their modifiable nature, may represent treatment targets in this population., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Over the last two decades, the conflicts in Iraq and Afghanistan have cost the United States significantly in terms of lives lost, disabling injuries, and budgetary expenditures. This manuscript calculates the differences in costs between veterans with combat injuries vs veterans without combat injuries. This work could be used to project future costs in subsequent studies., Materials and Methods: In this retrospective cohort study, we randomly selected 7,984 combat-injured veterans between February 1, 2002, and June 14, 2016, from Veterans Affairs Health System administrative data. We matched injured veterans 1:1 to noninjured veterans on year of birth (± 1 year), sex, and first service branch. We observed patients for a maximum of 10 years. This research protocol was reviewed and approved by the David Grant USAF Medical Center institutional review board (IRB), the University of Utah IRB, and the Research Review Committee of the VA Salt Lake City Health Care System in accordance with all applicable Federal regulations., Results: Patients were primarily male (98.1% in both groups) and White (76.4% for injured patients, 72.3% for noninjured patients), with a mean (SD) age of 26.8 (6.6) years for the injured group and 27.7 (7.0) years for noninjured subjects. Average total costs for combat-injured service members were higher for each year studied. The difference was highest in the first year ($16,050 compared to $4,135 for noninjured). These differences remained significant after adjustment. Although this difference was greatest in the first year (marginal effect $12,386, 95% confidence interval $9,736-$15,036; P < 0.001), total costs continued to be elevated in years 2-10, with marginal effects ranging from $1,766 to $2,597 (P < 0.001 for all years). More severe injuries tended to increase costs in all categories., Conclusions: Combat injured patients have significantly higher long-term health care costs compared to their noninjured counterparts. If this random sample is extrapolated to the 53,251 total of combat wounded service members, it implies a total excess cost of $1.6 billion to date after adjustment for covariates and a median follow-up time of 10 years. These costs are likely to increase as injured veterans age and develop additional chronic conditions., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Introduction: Examinations of risk factors for suicide attempt in United States service members at high risk of mental health diagnoses, such as those with combat injuries, are essential to guiding prevention and intervention efforts., Methods: Retrospective cohort study of 8727 combat-injured patients matched to deployed, non-injured patients utilizing Department of Defense and Veterans Affairs administrative records., Results: Combat injury was positively associated with suicide attempt in the univariate model (HR = 1.75, 95% CI 1.5-2.1), but lost significance after adjustment for mental health diagnoses. Utilizing Latent Transition Analysis in the combat-injured group, we identified five mental/behavioral health profiles: (1) Few mental health diagnoses, (2) PTSD and depressive disorders, (3) Adjustment disorder, (4) Multiple mental health comorbidities, and (5) Multiple mental health comorbidities with alcohol use disorder (AUD). Multiple mental health comorbidities with AUD had the highest suicide attempt rate throughout the study and more than four times that of Multiple mental health comorbidities in the first study year (23.4 vs. 5.1 per 1000 person years, respectively)., Conclusion: Findings indicate that (1) combat injury's impact on suicide attempt is attenuated by mental health and (2) AUD with multiple mental health comorbidities confers heightened suicide attempt risk in combat-injured service members., (© 2022 American Association of Suicidology. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Sepsis is caused by the host response to an infectious organism. It is common among hospitalized patients and is associated with significant morbidity and mortality. The current standard of care for sepsis is predominantly supportive, with early detection followed by prompt antibiotic administration. While this approach has undoubtedly improved patient outcomes, it has significant limitations. First, mortality from sepsis remains unacceptably high. Second, emerging pathogen resistance to antimicrobial therapies threatens a return to the pre-antimicrobial era of patient care. Lastly, the early stages of a pandemic (e.g., the recent coronavirus 19 pandemic) lack effective therapeutics. Given these limitations, novel treatment strategies are needed to advance the field and care for patients. One potential class of therapy is extracorporeal blood purification (EBP). While EBP is a broad classification, encompassing a wide range of techniques, this article will focus on three emerging EBP therapies that have been shown to bind and remove a wide variety of viral, bacterial, and fungal pathogens directly from circulation. These devices utilize different mechanisms of action for pathogen removal. The Seraph® 100 is composed of heparin coated beads. The Hemopurifier® combines the concept of plasma exchange with mannose-binding lectin (MBL). Lastly, the GARNET® utilizes a MBL fused to an IgG antibody. Via these mechanisms, these devices have been demonstrated to remove pathogens and pathogen-associated molecular patterns. The hope is that by directly removing pathogens, these EBP techniques may result in the biggest breakthrough in the management of sepsis since the advent of antibiotics almost 100 years ago., (© 2023 S. Karger AG, Basel.)

Introduction: The Seraph® 100 Microbind® Affinity Blood Filter (Seraph 100) is a hemoperfusion device that can remove pathogens from central circulation. However, the effect of Seraph 100 on achieving pharmacodynamic (PD) targets is not well described. We sought to determine the impact of Seraph 100 on ability to achieve PD targets for commonly used antibiotics., Methods: Estimates of Seraph 100 antibiotic clearance were obtained via literature. For vancomycin and gentamicin, published pharmacokinetic models were used to explore the effect of Seraph 100 on ability to achieve probability of target attainment (PTA). For meropenem and imipenem, the reported effect of continuous kidney replacement therapy (CKRT) on achieving PTA was used to extrapolate decisions for Seraph 100., Results: Seraph 100 antibiotic clearance is likely less than 0.5 L/h for most antibiotics. Theoretical Seraph 100 clearance up to 0.5 L/h and 2 L/h had a negligible effect on vancomycin PTA in virtual patients with creatinine clearance (CrCl) = 14 mL/min and CrCl >14 mL/min, respectively. Theoretical Seraph 100 clearance up to 0.5 L/h and 2 L/h had a negligible effect on gentamicin PTA in virtual patients with CrCl = 120 mL/min and CrCl <60 mL/min, respectively. CKRT intensity resulting in antibiotic clearance up to 2 L/h generally does not require dose increases for meropenem or imipenem. As Seraph 100 is prescribed intermittently and likely contributes far less to antibiotic clearance, dose increases would also not be required., Conclusion: Seraph 100 clearance of vancomycin, gentamicin, meropenem, and imipenem is likely clinically insignificant. There is insufficient evidence to recommend increased doses. For aminoglycosides, we recommend extended interval dosing and initiating Seraph 100 at least 30 min to 1 h after completion of infusion to avoid the possibility of interference with maximum concentrations., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Previous studies have identified combat exposure and combat traumatic experience as problematic drinking risk factors. Increasing evidence suggests that opioid use increases the risk of alcohol use disorder. This study investigated the association between opioid prescription use after injury and (1) alcohol use disorder and (2) severity of alcohol use disorder among deployed military servicemembers., Methods: Deidentified health records data of 9,029 deployed servicemembers from a retrospective cohort study were analyzed. Data were randomly selected from the Department of Defense Trauma Registry and included servicemembers with combat injuries during deployment in Iraq or Afghanistan (2002-2016). Pharmacy records and International Classification of Diseases, Ninth and Tenth Revision diagnosis codes were used. Three groups were identified (no opioid prescription use, nonpersistent opioid prescription use, and persistent opioid prescription use) and were compared on the basis of alcohol use disorder risk using Cox proportional hazard models. Data analyses were performed in 2021., Results: Of the 9,029 servicemembers with combat injury, 2,262 developed alcohol use disorder (1,322 developed severe alcohol use disorder). Compared with no opioid prescription use, increased alcohol use disorder risk was associated with persistent opioid prescription use, with a hazard ratio of 1.13 (95% CI=1.02, 1.26). After covariate adjustment, increased risk remained statistically significant (hazards ratio=1.24; 95% CI=1.10, 1.39). There was no significant difference in alcohol use disorder risk between no opioid prescription use and nonpersistent opioid prescription use. The risk of severe alcohol use disorder did not vary by opioid use among servicemembers with alcohol use disorder diagnosis., Conclusions: The findings of the study suggest that the incidence of alcohol use disorder was higher among injured servicemembers with persistent opioid prescription use than among those without opioid use. If replicated in prospective studies, the findings highlight the need for clinicians to consider the current and history of alcohol use of patients in initiating treatment involving opioids., (Published by Elsevier Inc.)

Importance: Traumatic brain injury (TBI) was common among US service members deployed to Iraq and Afghanistan. Although there is some evidence to suggest that TBI increases the risk of cardiovascular disease (CVD), prior reports were predominantly limited to cerebrovascular outcomes. The potential association of TBI with CVD has not been comprehensively examined in post-9/11-era veterans., Objective: To determine the association between TBI and subsequent CVD in post-9/11-era veterans., Design, Setting, and Participants: This was a retrospective cohort study conducted from October 1, 1999, to September 30, 2016. Participants were followed up until December 31, 2018. Included in the study were administrative data from the US Department of Veterans Affairs and the Department of Defense from the Long-term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium. Participants were excluded if dates did not overlap with the study period. Data analysis was conducted between November 22, 2021, and June 28, 2022., Exposures: History of TBI as measured by diagnosis in health care records., Main Outcomes and Measures: Composite end point of CVD: coronary artery disease, stroke, peripheral artery disease, and cardiovascular death., Results: Of the 2 530 875 veterans from the consortium, after exclusions, a total of 1 559 928 veterans were included in the analysis. A total of 301 169 veterans (19.3%; median [IQR] age, 27 [23-34] years; 265 217 male participants [88.1]) with a TBI history and 1 258 759 veterans (80.7%; median [IQR] age, 29 [24-39] years; 1 012 159 male participants [80.4%]) without a TBI history were included for analysis. Participants were predominately young (1 058 054 [67.8%] <35 years at index date) and male (1 277 376 [81.9%]). Compared with participants without a history of TBI, diagnoses of mild TBI (hazard ratio [HR], 1.62; 95% CI, 1.58-1.66; P < .001), moderate to severe TBI (HR, 2.63; 95% CI, 2.51-2.76; P < .001), and penetrating TBI (HR, 4.60; 95% CI, 4.26-4.96; P < .001) were associated with CVD in adjusted models. In analyses of secondary outcomes, all severities of TBI were associated with the individual components of the composite outcome except penetrating TBI and CVD death., Conclusions and Relevance: Results of this cohort study suggest that US veterans with a TBI history were more likely to develop CVD compared with veterans without a TBI history. Given the relatively young age of the cohort, these results suggest that there may be an increased burden of CVD as these veterans age and develop other CVD risk factors. Future studies are needed to determine if the increased risk associated with TBI is modifiable.

In late 2019, a novel betacoronavirus, later termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was discovered in patients with an unknown respiratory illness in Wuhan, China. SARS-CoV-2 and the disease caused by the novel coronavirus, coronavirus disease 2019 (COVID-19), spread rapidly and resulted in the World Health Organization declaring a pandemic in March 2020. In a minority of patients infected with SARS-CoV-2, severe illness develops characterized by a dysregulated immune response, acute respiratory distress syndrome, and multisystem organ failure. Despite the development of antiviral and multiple immunomodulatory therapies, outcomes of severe illness remain poor. In response, the Food and Drug Administration in the United States authorized the emergency use of several extracorporeal blood purification (EBP) devices for critically ill patients with COVID-19. Extracorporeal blood purification devices target various aspects of the host response to infection to reduce immune dysregulation. This review highlights the underlying technology, currently available literature on use in critically ill COVID-19 patients, and future studies involving four EBP platforms: 1) oXiris filter, 2) CytoSorb filter, 3) Seraph 100 Microbind blood affinity filter, and 4) the Spectra Optia Apheresis System with the Depuro D2000 Adsorption Cartridge., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASAIO.)

Cognitive difficulties typically resolve within days to weeks following mild traumatic brain injury (mTBI); however, a sizable proportion of individuals continue to report cognitive symptoms months to years later that are often associated with posttraumatic stress disorder (PTSD) and depression to a greater degree than a history of mTBI. The current study sought to evaluate the prevalence of self-reported cognitive difficulties as well as the relative contributions of demographic, injury-related, and mental health variables in a large study of U.S. military personnel injured during deployment since 2001. Slightly fewer than half (42.0%) of participants reported elevated cognitive difficulties compared with a normative population; however, this was driven primarily by those who screened positive for PTSD or depression. Hierarchical linear regression revealed that various demographic and injury factors, including lower educational attainment, retired or separated military status, enlisted rank, and a history of deployment-related mTBI, were associated with more self-reported cognitive difficulties, f 2 = 0.07. Screening positive for PTSD or depression accounted for 32.1% of the variance in self-reported cognitive symptoms, f 2 = 0.63, whereas injury variables, including a history of deployment-related mTBI, albeit significant in the model, accounted for 1.6%. The current findings add to the growing body of literature underscoring the importance of screening for and treating mental health conditions in injured military personnel., (Published 2022. This article is a U.S. Government work and is in the public domain in the USA.)

Introduction: Although retrospective analyses have found that combat-injured service members are at high risk for mental and physical health outcomes following injury, relatively little is known about the long-term health of injured service members. To better understand long-term health outcomes after combat injury, a large, prospective observational cohort collecting both subjective and objective health data is needed. Given that a study of this nature would be costly and face many logistical challenges, we first conducted a pilot to assess the feasibility of a larger, definitive study., Materials and Methods: We ran a prospective, observational pilot study of 119 combat-injured service members and veterans who completed (1) at least one set of laboratory measurements (blood and urine sample collection and vitals measurements) at Clinical Laboratory Improvement Amendment of 1988 compliant laboratory locations and (2) at least one online assessment for the Wounded Warrior Recovery Project (WWRP), a 15-year examination of patient-reported outcomes among service members injured on combat deployment. We recruited the pilot study cohort from WWRP participants who met eligibility criteria and indicated interest in additional research opportunities. We collected laboratory values and patient-reported outcomes at baseline and again 1 year later, and obtained demographic, injury, and military service data from the Expeditionary Medical Encounter Database. The David Grant USAF Medical Center Institution Review Board (IRB) and the Naval Health Research Center IRB reviewed and approved the study protocols., Results: During recruitment for the pilot study, 624 study candidates were identified from WWRP. Of the 397 candidates we contacted about the pilot study, 179 (45.1%) enrolled and 119 (66.4%) of those who enrolled completed the first year of participation. The second study year was suspended due to the coronavirus disease-2019 pandemic. At the time of suspension, 72 (60.5%) participants completed follow-up laboratory appointments, and 111 (93.3%) completed second-year WWRP assessments. Participants in the pilot study were predominately male (95.0%) and non-Hispanic White (55.5%), with a median (interquartile range) age of 38.3 (34.1-45.4) years., Conclusions: Collection of patient-reported outcomes and laboratory samples in a geographically dispersed cohort of combat-injured service members is possible. While significant challenges exist, our pilot study results indicate that a larger, longitudinal, cohort study is feasible., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2021. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Objectives: To assess traumatic brain injury (TBI)-related risks factors for early-onset dementia (EOD)., Background: Younger Post-9/11 Veterans may be at elevated risk for EOD due to high rates of TBI in early/mid adulthood. Few studies have explored the longitudinal relationship between traumatic brain injury (TBI) and the emergence of EOD subtypes., Methods: This matched case-control study used data from the Veterans Health Administration (VHA) to identify Veterans with EOD. To address the low positive predictive value (PPV = 0.27) of dementia algorithms in VHA records, primary outcomes were Alzheimer's disease (AD) and frontotemporal dementia (FTD). Logistic regression identified conditions associated with dementia subtypes., Results: The EOD cohort included Veterans with AD (n = 689) and FTD (n = 284). There were no significant demographic differences between the EOD cohort and their matched controls. After adjustment, EOD was significantly associated with history of TBI (OR: 3.05, 2.42-3.83), epilepsy (OR: 4.8, 3.3-6.97), other neurological conditions (OR: 2.0, 1.35-2.97), depression (OR: 1.35, 1.12-1.63) and cardiac disease (OR: 1.36, 1.1-1.67)., Conclusion: Post-9/11 Veterans have higher odds of EOD following TBI. A sensitivity analysis across TBI severity confirmed this trend, indicating that the odds for both AD and FTD increased after more severe TBIs.

The Seraph100 Microbind Affinity Blood Filter (Seraph 100) (ExThera Medical, Martinez, CA) is an extracorporeal therapy that can remove pathogens from blood, including severe acute respiratory syndrome coronavirus 2. The aim of this study was to evaluate safety and efficacy of Seraph 100 treatment for COVID-19., Design: Retrospective cohort study., Setting: Nine participating ICUs., Patients: COVID-19 patients treated with Seraph 100 ( n = 53) and control patients matched by study site ( n = 53)., Intervention: Treatment with Seraph 100., Measurements and Main Results: At baseline, there were no differences between the groups in terms of sex, race/ethnicity, body mass index, and need for mechanical ventilation. However, patients in the Seraph 100 group were younger (median age, 54 yr; interquartile range [IQR], 41-65) compared with controls (median age, 64 yr; IQR, 56-69; p = 0.009). Charlson comorbidity index scores were lower in the Seraph 100 group (2; IQR, 0-3) compared with the control group (3; IQR, 2-4; p = 0.006). Acute Physiology and Chronic Health Evaluation II scores were also lower in Seraph 100 subjects (12; IQR, 9-17) compared with controls (16; IQR, 12-21; p = 0.011). The Seraph 100 group had higher vasopressor-free days with an incidence rate ratio of 1.30 on univariate analysis. This difference was not significant after adjustment. Seraph 100-treated subjects were less likely to die compared with controls (32.1% vs 64.2%; p = 0.001), a difference that remained significant after adjustment. However, no difference in mortality was observed in a post hoc analysis utilizing an external control group. In the full cohort of 86 treated patients, there were 177 total treatments, in which only three serious adverse events were recorded., Conclusions: Although this study did not demonstrate consistently significant clinical benefit across all endpoints and comparisons, the findings suggest that broad spectrum, pathogen agnostic, blood purification can be safely deployed to meet new pathogen threats while awaiting targeted therapies and vaccines., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

The mechanisms by which lower limb ischemia/reperfusion induces acute kidney injury (AKI) remain largely uncharacterized. We hypothesized that tourniquet-induced lower limb ischemia/reperfusion (TILLIR) would inhibit mitochondrial function in the renal cortex. We used a murine model to show that TILLIR of the high thigh regions inflicted time-dependent AKI as determined by renal function and histology. This effect was associated with decreased activities of mitochondrial complexes I, II, V and citrate synthase in the kidney cortex. Moreover, TILLIR reduced mRNA levels of a master regulator of mitochondrial biogenesis PGC-1α, and its downstream genes NDUFS1 and ATP5o in the renal cortex. TILLIR also increased serum corticosterone concentrations. TILLIR did not significantly affect protein levels of the critical regulators of mitophagy PINK1 and PARK2, mitochondrial transport proteins Tom20 and Tom70, or heat-shock protein 27. TILLIR had no significant effect on mitochondrial oxidative stress as determined by mitochondrial ability to generate reactive oxygen species, protein carbonylation, or protein levels of MnSOD and peroxiredoxin1. However, TILLIR inhibited classic autophagic flux by increasing p62 protein abundance and preventing the conversion of LC3-I to LC3-II. TILLIR increased phosphorylation of cytosolic and mitochondrial ERK1/2 and mitochondrial AKT1, as well as mitochondrial SGK1 activity. In conclusion, lower limb ischemia/reperfusion induces distal AKI by inhibiting mitochondrial function through reducing mitochondrial biogenesis. This AKI occurs without significantly affecting PINK1-PARK2-mediated mitophagy or mitochondrial oxidative stress in the kidney cortex., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Importance: Emerging evidence suggests that harmful exposures during military service, such as traumatic brain injury (TBI), may contribute to mental health, chronic disease, and mortality risks., Objective: To assess the mortality rates and estimate the number of all-cause and cause-specific excess deaths among veterans serving after the September 11, 2001, terrorist attacks (9/11) with and without exposure to TBI., Design, Setting, and Participants: This cohort study analyzed administrative and mortality data from January 1, 2002, through December 31, 2018, for a cohort of US military veterans who served during the Global War on Terrorism after the 9/11 terrorist attacks. Veterans who served active duty after 9/11 with 3 or more years of care in the Military Health System or had 3 or more years of care in the Military Health System and 2 or more years of care in the Veterans Health Administration were included for analysis. The study used data from the Veterans Affairs/Department of Defense Identity Repository database, matching health records data from the Military Health Service Management Analysis and Reporting tool, the Veterans Health Administration Veterans Informatics and Computing Infrastructure, and the National Death Index. For comparison with the total US population, the study used the Centers for Disease Control and Prevention WONDER database. Data analysis was performed from June 16 to September 8, 2021., Exposure: Traumatic brain injury., Main Outcomes and Measures: Multivariable, negative binomial regression models were used to estimate adjusted all-cause and cause-specific mortality rates for the post-9/11 military veteran cohort, stratified by TBI severity level, and the total US population. Differences in mortality rates between post-9/11 military veterans and the total US population were used to estimate excess deaths from each cause of death., Results: Among 2 516 189 post-9/11 military veterans (2 167 736 [86.2%] male; and 45 324 [1.8%] American Indian/Alaska Native, 160 178 [6.4%], Asian/Pacific Islander, 259 737 [10.3%] Hispanic, 387 926 [15.4%] non-Hispanic Black, 1 619 834 [64.4%] non-Hispanic White, and 43 190 [1.7%] unknown), 17.5% had mild TBI and 3.0% had moderate to severe TBI; there were 30 564 deaths. Adjusted, age-specific mortality rates were higher for post-9/11 military veterans than for the total US population and increased with TBI severity. There were an estimated 3858 (95% CI, 1225-6490) excess deaths among all post-9/11 military veterans. Of these, an estimated 275 (95% CI, -1435 to 1985) were not exposed to TBI, 2285 (95% CI, 1637 to 2933) had mild TBI, and 1298 (95% CI, 1023 to 1572) had moderate to severe TBI. Estimated excess deaths were predominantly from suicides (4218; 95% CI, 3621 to 4816) and accidents (2631; 95% CI, 1929 to 3333). Veterans with moderate to severe TBI accounted for 33.6% of total excess deaths, 11-fold higher than would otherwise be expected., Conclusions and Relevance: This military veteran cohort experienced more excess mortality compared with the total US population than all combat deaths from 9/11/01 through 9/11/21, concentrated among individuals exposed to TBI. These results suggest that a focus on what puts veterans at risk for accelerated aging and increased mortality is warranted.

Study Objectives: Obstructive sleep apnea is prevalent among military members despite fewer traditional risk factors. We sought to determine the incidence and longitudinal predictors of obstructive sleep apnea in a large population of survivors of combat-related traumatic injury and a matched control group., Methods: Retrospective cohort study of military service members deployed to conflict zones from 2002-2016 with longitudinal follow-up in the Veterans Affairs and Military Health Systems. Two cohorts of service members were developed: (1) those who sustained combat injuries and (2) matched, uninjured participants., Results: 17,570 service members were retrospectively analyzed for a median of 8.4 years. After adjustment, traumatic brain injury (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.20-1.60), posttraumatic stress disorder (HR 1.24, 95% CI 1.05-1.46), depression (HR 1.52, 95% CI 1.30-1.79), anxiety (HR 1.40, 95% CI 1.21-1.62), insomnia (HR 1.71, 95% CI 1.44-2.02), and obesity (HR 2.40, 95% CI 2.09-2.74) were associated with development of obstructive sleep apnea. While combat injury was associated with obstructive sleep apnea in the univariate analysis (HR 1.25, 95% CI 1.17-1.33), the direction of this association was reversed in the multivariable model (HR 0.74, 95% CI 0.65-0.84). In a nested analysis, this was determined to be due to the effect of mental health diagnoses., Conclusions: The incidence of obstructive sleep apnea is higher among injured service members (29.1 per 1,000 person-years) compared to uninjured service members (23.9 per 1,000 person-years). This association appears to be driven by traumatic brain injury and the long-term mental health sequelae of injury., Citation: Haynes ZA, Stewart IJ, Poltavskiy EA, et al. Obstructive sleep apnea among survivors of combat-related traumatic injury: a retrospective cohort study. J Clin Sleep Med . 2022;18(1):171-179., (© 2022 American Academy of Sleep Medicine.)

Objective: To determine whether persistent opioid use after injury is associated with subsequent long-term development of clinically recognized opioid abuse., Summary Background Data: Opioid abuse is an epidemic in the United States and trauma can initiate persistent use; however, it remains unclear whether persistent opioid use contributes to the subsequent development of opioid abuse. The care of combat casualties by the Departments of Defense and Veterans Affairs uniquely allows investigation of this long-term outcome., Methods: This retrospective cohort study randomly selected 10,000 battle-injured United States military personnel. We excluded patients who died during initial hospitalization or within 180 days of discharge, had a preinjury opioid abuse diagnosis, or had missing data in a preselected variable. We defined persistent opioid use as filling an opioid prescription 3 to 6 months after discharge and recorded clinically recognized opioid abuse using relevant diagnosis codes., Results: After exclusion, 9284 subjects were analyzed, 2167 (23.3%) of whom developed persistent opioid use. During a median follow-up time of 8 years, 631 (6.8%) patients developed clinically recognized opioid abuse with a median time to diagnosis of 3 years. Injury severity and discharge opioid prescription amount were associated with persistent opioid use after trauma. After adjusting for patient and injury-specific factors, persistent opioid use was associated with the long-term development of clinically recognized opioid abuse (adjusted hazard ratio, 2.39; 95% confidence interval, 1.99-2.86)., Conclusions: Nearly a quarter of patients filled an opioid prescription 3 to 6 months after discharge, and this persistent use was associated with long-term development of opioid abuse., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Dialysis patients may not have access to conventional renal replacement therapy (RRT) following disasters. We hypothesized that improvised renal replacement therapy (ImpRRT) would be comparable to continuous renal replacement therapy (CRRT) in a porcine acute kidney injury model., Methods: Following bilateral nephrectomies and 2 hours of caudal aortic occlusion, 12 pigs were randomized to 4 hours of ImpRRT or CRRT. In the ImpRRT group, blood was circulated through a dialysis filter using a rapid infuser to collect the ultrafiltrate. Improvised replacement fluid, made with stock solutions, was infused pre-pump. In the CRRT group, commercial replacement fluid was used. During RRT, animals received isotonic crystalloids and norepinephrine., Results: There were no differences in serum creatinine, calcium, magnesium, or phosphorus concentrations. While there was a difference between groups in serum potassium concentration over time (P < 0.001), significance was lost in pairwise comparison at specific time points. Replacement fluids or ultrafiltrate flows did not differ between groups. There were no differences in lactate concentration, isotonic crystalloid requirement, or norepinephrine doses. No difference was found in electrolyte concentrations between the commercial and improvised replacement solutions., Conclusion: The ImpRRT system achieved similar performance to CRRT and may represent a potential option for temporary RRT following disasters.

Study Objectives: Insomnia is a diagnosis with broad health and economic implications that has been increasingly recognized in military service members. This trend was concurrent with an increase in traumatic wartime injuries. Accordingly, we sought to determine longitudinal predictors of persistent insomnia in combat veterans who sustained traumatic injuries., Methods: Retrospective cohort study of service members deployed to conflict zones from 2002 to 2016, with longitudinal follow-up in the Veterans Affairs and Military Health Systems. Two cohorts were derived: (1) service members who sustained traumatic injuries and (2) an age-, sex-, and service component-matched cohort of uninjured service members who deployed to a combat zone. Insomnia was defined using International Classification of Diseases, Ninth Revision or International Classification of Diseases, 10th Revision-Clinical Modification codes., Results: The final population of 17,374 service members was followed from date of injury (or date of matched participant's injury) for a median of 8.4 (interquartile range, 5.3-10.7) years. Service members with traumatic injury were at significantly greater risk of developing insomnia than uninjured service members (hazard ratio = 1.43; 95% confidence interval, 1.30-1.58) after adjustment. Traumatic brain injury was associated with insomnia compared with patients without traumatic brain injury in the multivariable model: mild/unclassified traumatic brain injury (hazard ratio = 2.07; 95% confidence interval, 1.82-2.35) and moderate/severe/ penetrating traumatic brain injury (hazard ratio = 2.43; 95% confidence interval, 2.06-2.86). Additionally, burn injury (hazard ratio = 1.95; 95% confidence interval, 1.47-2.59) and amputation (hazard ratio = 1.61; 95% confidence interval, 1.26-2.06) significantly increased the risk of a diagnosis., Conclusions: Traumatic injuries significantly predicted a diagnosis of insomnia after controlling for mental health disorders. Our findings strongly suggest the need for long-term surveillance of sleep disorders in trauma survivors., Citation: Haynes ZA, Collen JF, Poltavskiy EA, et al. Risk factors of persistent insomnia among survivors of traumatic injury: a retrospective cohort study. J Clin Sleep Med. 2021;17(9):1831-1840., (© 2021 American Academy of Sleep Medicine.)

Introduction: Atrial fibrillation and atrial flutter (AF/AFL), the most common atrial arrhythmias, have never been examined in combat casualties. In this study, we investigated the impact of traumatic injury on AF/AFL among service members with deployment history., Methods: Sampled from the Department of Defense (DoD) Trauma Registry (n = 10,000), each injured patient in this retrospective cohort study was matched with a non-injured service member drawn from the Veterans Affairs/DoD Identity Repository. The primary outcome was AF/AFL diagnosis identified using ICD-9-CM and ICD-10-CM codes. Competing risk regressions based on Fine and Gray subdistribution hazards model with were utilized to assess the association between injury and AF/AFL., Results: There were 130 reported AF/AFL cases, 90 of whom were injured and 40 were non-injured. The estimated cumulative incidence rates of AF/AFL for injured was higher compared to non-injured patients (hazards ratio [HR] = 2.04; 95% confidence interval [CI] = 1.44, 2.87). After adjustment demographics and tobacco use, the association did not appreciably decrease (HR = 1.90; 95% CI = 1.23, 2.93). Additional adjustment for obesity, hypertension, diabetes, and vascular disorders, the association between injury and AF/AFL was no longer statistically significant (HR = 1.51; 95% CI = 0.99, 2.52)., Conclusion: Higher AF/AFL incidence rate was observed among deployed service members with combat injury compared to servicemembers without injury. The association did not remain significant after adjustment for cardiovascular-related covariates. These findings highlight the need for combat casualty surveillance to further understand the AF/AFL risk within the military population and to elucidate the potential underlying pathophysiologic mechanisms., (© 2021 Wiley Periodicals LLC.)

Background: The relationship between traumatic injury and subsequent mental health diagnoses is not well understood and may have significant implications for patient screening and clinical intervention. We sought to determine the adjusted association between traumatic injury and the subsequent development of post-traumatic stress disorder (PTSD), depression, and anxiety., Methods: Using Department of Defense and Veterans Affairs datasets between February 2002 and June 2016, we conducted a retrospective cohort study of 7,787 combat-injured United States service members matched 1:1 to combat-deployed, uninjured service members. The primary exposure was combat injury versus no combat injury. Outcomes were diagnoses of PTSD, depression, and anxiety, defined by International Classification of Diseases 9th and 10th Revision Clinical Modification codes., Results: Compared to noninjured service members, injured service members had higher observed incidence rates per 100 person-years for PTSD (17.1 vs. 5.8), depression (10.4 vs. 5.7), and anxiety (9.1 vs. 4.9). After adjustment, combat-injured patients were at increased risk of development of PTSD (HR 2.92, 95%CI 2.68-3.17), depression (HR 1.47, 95%CI 1.36-1.58), and anxiety (HR 1.34, 95%CI 1.24-1.45)., Conclusions: Traumatic injury is associated with subsequent development of PTSD, depression, and anxiety. These findings highlight the importance of increased screening, prevention, and intervention in patients with exposure to physical trauma., (© 2021 The McConnell Group, Inc. Brain and Behavior published by Wiley Periodicals LLC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Background: Traditionally, patient risk scoring is done by evaluating vital signs and clinical severity scores with clinical intuition. Urinary biomarkers can add objectivity to these models to make risk prediction more accurate. We used metabolomics to identify prognostic urinary biomarkers of mortality or need for renal replacement therapy (RRT). Additionally, we assessed acute kidney injury (AKI) diagnosis, injury severity score (ISS), and AKI stage., Methods: Urine samples (n = 82) from a previous study of combat casualties were evaluated using proton nuclear magnetic resonance ( 1 H-NMR) spectroscopy. Chenomx software was used to identify and quantify urinary metabolites. Metabolite concentrations were normalized by urine output, autoscaled, and log-transformed. Partial least squares discriminant analysis (PLS-DA) and statistical analysis were performed. Receiver operating characteristic (ROC) curves were used to assess prognostic utility of biomarkers for mortality and RRT., Results: Eighty-four (84) metabolites were identified and quantified in each urine sample. Of these, 11 were identified as drugs or drug metabolites and excluded. The PLS-DA models for ISS and AKI diagnosis did not have acceptable model statistics. Therefore, only mortality/RRT and AKI stage were analyzed further. Of 73 analyzed metabolites, 9 were significantly associated with mortality/RRT (p < 0.05) and 11 were significantly associated with AKI stage (p < 0.05). 1-Methylnicotinamide was the only metabolite to be significantly associated (p < 0.05) with all outcomes and was significantly higher (p < 0.05) in patients with adverse outcomes. Elevated lactate and 1-methylnicotinamide levels were associated with higher AKI stage and mortality and RRT, whereas elevated glycine levels were associated with patients who survived and did not require RRT, or had less severe AKI. ROC curves for each of these metabolites and the combined panel had good predictive value (lactate AUC = 0.901, 1-methylnicotinamide AUC = 0.864, glycine AUC = 0.735, panel AUC = 0.858)., Conclusions: We identified urinary metabolites associated with AKI stage and the primary outcome of mortality or need for RRT. Lactate, 1-methylnicotinamide, and glycine may be used as a panel of predictive biomarkers for mortality and RRT. 1-Methylnicotinamide is a novel biomarker associated with adverse outcomes. Additional studies are necessary to determine how these metabolites can be utilized in clinically-relevant risk prediction models.

Background: A better understanding of the long-term health effects of combat injury is important for the management of veterans' health in the Department of Defense (DoD) and Veterans Affairs (VA) health care systems and may have implications for primary care management of civilian trauma patients., Objective: To determine the impact of traumatic injury on the subsequent development of hypertension (HTN), diabetes mellitus (DM), and coronary artery disease (CAD) after adjustment for sociodemographic, health behavior, and mental health factors., Design: Retrospective cohort study of current and former US military personnel with data obtained from both the DoD and VA health care systems., Participants: Combat injured (n = 8727) service members between 1 February 2002 and 14 June 2016 randomly selected from the DoD Trauma Registry matched 1:1 based on year of birth, sex, and branch of service to subjects that deployed to a combat zone but were not injured., Main Measures: Traumatic injury, stratified by severity, compared with no documented injury. Diagnoses of HTN, DM, and CAD defined by International Classification of Diseases 9th or 10th Revision Clinical Modification codes., Key Results: After adjustment, severe traumatic injury was significantly associated with HTN (HR 2.78, 95% CI 2.18-3.55), DM (HR 4.45, 95% CI 2.15-9.18), and CAD (HR 4.87, 95% CI 2.11-11.25), compared with no injury. Less severe injury was associated with HTN (HR 1.14, 95% CI 1.05-1.24) and CAD (HR 1.62, 95% CI 1.11-2.37)., Conclusions: Severe traumatic injury is associated with the subsequent development of HTN, DM, and CAD. These findings have profound implications for the primary care of injured service members in both the DoD/VA health systems and may be applicable to civilian trauma patients as well. Further exploration of pathophysiologic, health behavior, and mental health changes after trauma is warranted to guide future intervention strategies.

A growing body of literature on military personnel and veterans' health suggests that prior military service may be associated with exposures that increase the risk of cardiovascular disease (CVD), which may differ by race/ethnicity. This study examined the hypothesis that differential telomere shortening, a measure of cellular aging, by race/ethnicity may explain prior findings of differential CVD risk in racial/ethnic groups with military service. Data from the first two continuous waves of the National Health and Nutrition Examination Survey (NHANES), administered from 1999-2002 were analyzed. Mean telomere length in base pairs was analyzed with multivariable adjusted linear regression with complex sample design, stratified by sex. The unadjusted mean telomere length was 225.8 base shorter for individuals with prior military service. The mean telomere length for men was 47.2 (95% CI: -92.9, -1.5; p < 0.05) base pairs shorter for men with military service after adjustment for demographic, socioeconomic, and behavioral variables, but did not differ significantly in women with and without prior military service. The interaction between military service and race/ethnicity was not significant for men or women. The results suggest that military service may contribute to accelerated aging as a result of health damaging exposures, such as combat, injury, and environmental contaminants, though other unmeasured confounders could also potentially explain the results.

While extensive research using animal models has improved the understanding of acute kidney injury (AKI), this knowledge has not been translated into effective treatments. Many promising interventions for AKI identified in mice and rats have not been validated in subsequent clinical trials. As a result, the mortality rate of AKI patients remains high. Inflammation plays a fundamental role in the pathogenesis of AKI, and one reason for the failure to translate promising therapeutics may lie in the profound difference between the immune systems of rodents and humans. The immune systems of large animals such as swine, nonhuman primates, sheep, dogs and cats, more closely resemble the human immune system. Therefore, in the absence of a basic understanding of the pathophysiology of human AKI, large animals are attractive models to test novel interventions. However, there is a lack of reviews on large animal models for AKI in the literature. In this review, we will first highlight differences in innate and adaptive immunities among rodents, large animals, and humans in relation to AKI. After illustrating the potential merits of large animals in testing therapies for AKI, we will summarize the current state of the evidence in terms of what therapeutics have been tested in large animal models. The aim of this review is not to suggest that murine models are not valid to study AKI. Instead, our objective is to demonstrate that large animal models can serve as valuable and complementary tools in translating potential therapeutics into clinical practice.

Background: Renal cystic disease arising from various etiologies results in fluid-filled cavities within the kidneys. Moreover, preexisting renal dysfunction has been shown to exacerbate multiple pathologies. While swine bred for biomedical research are often clinically inspected for illness/parasites, more advanced diagnostics may aid in uncovering underlying renal abnormalities., Methods: Computed tomography was performed in 54 female prepubertal Yorkshire swine to characterize renal cysts; urine and blood chemistry, and histology of cysts were also performed., Results: Digital reconstruction of right and left kidneys demonstrated that roughly one-third of the animals (17/54; 31%) had one or more renal cyst. Circulating biomarkers of renal function were not different between animals that had cysts and those that did not. Alternatively, urinary glucose ( P  = .03) was higher and sodium ( P  = .07) tended to be lower in animals with cysts compared to animals without, with no differences in protein ( P  = .14) or potassium ( P = .20). Aspiration of cystic fluid was feasible in two animals, which revealed that the cystic fluid urea nitrogen (97.6 ± 28.7 vs 911.3 ± 468.2 mg/dL), potassium (29.8 ± 14.4 vs 148.2 ± 24.85 mmol/L), uric acid (2.55 ± 1.35 vs 11.4 ± 5.65 mg/dL), and creatinine (60.34 ± 17.26 vs 268.99 ± 95.79 mg/dL) were much lower than in the urine. Histology demonstrated a cyst that markedly compresses the adjacent cortex and is lined by a single layer of flattened epithelium, bounded by fibrous connective tissue which extends into the parenchyma. There is tubular atrophy and loss in these areas., Conclusion: This study provides valuable insight for future studies focusing on kidney function in swine bred for biomedical research., Competing Interests: None., (Published 2020. This article is a U.S. Government work and is in the public domain in the USA. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

Background: Although the long-term effects of combat injury are not well understood, there is emerging concern that exposure to combat environments and subsequent injury may increase the risk of hypertension through changes in inflammatory responses, psychological stress and mental health, and health behaviors., Methods: Data from the Millennium Cohort Study and the Department of Defense Trauma Registry were used to identify combat-exposed and combat-injured participants. Incident hypertension diagnoses were ascertained from the Millennium Cohort survey. The associations between combat exposure/injury and hypertension risk was estimated using multivariable complementary log-log survival models., Results: The final analysis sample consisted of 38 734 participants. Of these, 50.8% deployed but were not exposed to combat, 48.6% deployed and were exposed to combat, and 0.6% had combat injury. Overall prevalence of hypertension was 7.6%. Compared with participants who deployed but did not experience combat (mild exposure), elevated odds of hypertension were observed among those who experienced combat but not wounded (moderate exposure; AOR, 1.28; 95% CI, 1.19-1.38) and those wounded in combat (high exposure; AOR, 1.46; 95% CI, 1.07-2.00). Sleep duration of less than 4 h (AOR, 1.21; 95% CI, 1.03-1.43), sleep duration of 4-6 h (AOR, 1.16; 95% CI, 1.05-1.29), posttraumatic stress disorder (AOR, 1.54; 95% CI, 1.26-1.87), and overweight (AOR, 1.77; 95% CI, 1.61-1.95) and obese (AOR, 2.77; 95% CI, 2.45-3.12) status were also associated with higher odds of hypertension., Conclusion: Results support the hypotheses that combat exposure increases hypertension risk and that combat injury exacerbates this risk.

Acute kidney injury (AKI) is associated with high mortality in burn patients. Urinary biomarkers can aid in the prediction of AKI and its consequences, such as death and the need for renal replacement therapy (RRT). The purpose of this study was to investigate a novel methodology for detecting urinary biomarkers, the NephroCheck® Test System, and assess its ability to predict death or the need for RRT in burn patients. Burn patients admitted to the United States Army Institute of Surgical Research (USAISR) burn intensive care unit were prospectively enrolled between March 2016 and April 2018. A urine sample was obtained from all study participants using the NephroCheck® system. Patient and injury characteristics were gathered, and descriptive statistics were calculated and multivariable logistic regression analyses were performed using these data. Of the 69 patients in this study, 15 patients (21.7%) attained the composite outcome of death or needing RRT within 30 days of urine collection. NephroCheck® scores were higher for patients with the composite outcome, with P = 0.06 for centrifuged scores and P = 0.04 for noncentrifuged scores. Centrifuged and noncentrifuged scores were in high agreement and correlation (R2 = 0.97, P < 0.0001). Noncentrifuged scores were significant in the unadjusted analysis, but they were not significant in the adjusted analysis. Although these scores had a lower sensitivity and negative predictive value compared with other parameters, they had the second highest specificity and positive predictive value. NephroCheck® scores were higher in burn patients with the composite outcome of death or needing RRT, and they demonstrated comparable sensitivity and specificity to creatinine and TBSA., (Published by Oxford University Press on behalf of the American Burn Association 2020.)

Accurate assessment of coagulation in porcine studies is essential. We sought to establish normal values for porcine rotational thromboelastometry (ROTEM) according to the American Society for Veterinary Clinical Pathology guidelines and to assess the effects of various preanalytical parameters on those measurements. Healthy Yorkshire-cross pigs ( n = 81; 46 males and 35 females) were anesthetized. By using a 18-gauge needle attached to a vacuum phlebotomy tube, blood was acquired from the cranial vena cava. Tubes were filled in the following order: evacuation clot tube, EDTA tube, heparin tube, and 2 citrate tubes. The citrate tubes were randomly assigned to 30 min with or without constant agitation on a rocker. The following parameters were reported according to the manufacturer's recommendations: clotting time, clot formation time, α, (tangent to the clot formation curve when the clot firmness is 20 mm), clot firmness after 10 and 20 min, maximal clot firmness, maximum lysis, and lysis indexes at 30 and 45 min. Reference intervals were reported as mean ± 2 SD (parametric distribution) or 2.5th and 97.5th percentile of the population's results (nonparametric distribution). The effects of sex, sampling order, and agitation on ROTEM results were analyzed through linear regression. Neither sex nor sample agitation influenced any of the ROTEM parameters. Combined reference intervals were established for each ROTEM parameter by pooling data from the nonagitated tubes for both male and female pigs. This study is the first to establish ROTEM reference intervals from a large number of male and female adult Yorkshire-cross pigs and to provide a detailed description of preanalytical sample processing.