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Abstract Background The pathogenetic mechanisms that underlie the interstitial lung disease cryptogenic fibrosing alveolitis (CFA) may involve an immunological reaction to unidentified antigens in the lung, resulting in tissue damage. Method In order to identify the range of target autoantigens, we used expression cloning, employing serum from an index patient as the probe against an expressed cDNA library that was derived from a tumour cell line. We screened over 5 × 105 recombinants and obtained sequence information on three antigens that had provoked strong responses with immunoglobulin heavy chain class switching, presumably as a consequence of T-cell recognition. Results All of the antigens were identifiable by comparison with sequence data from the US National Center for Biotechnology Information. Alanyl tRNA synthetase (ATS) was picked on six occasions; five of these incidences reflected independent recombination events, indicating that the library was not biased. Antibodies to ATS (anti-PL-12) represent the most common reactivity that defines the antisynthetase syndrome, which is typically expressed as polymyositis, dermatomyositis and interstitial lung disease (ILD). The index patient never showed symptoms other than those associated with alveolitis, even though sera obtained from him over a period of 2 years contained antibodies with the same specificity. Autoantibodies to ATS were never detected in serial bleeds from 11 other patients with CFA, and neither did we detect antibodies to the other two antigens identified from the serum of the index patient. Conclusion The humoral response in patients with CFA can be dominated by autoantibodies with private specificities. This suggests that the antibodies are epiphenomenal and are a secondary feature of tissue damage induced by some other mechanism.

Abstract Background New Zealand Māori have a poorer outcome from breast cancer than non-Māori, yet prognostic data are sparse. The objective of this study was to quantify levels of prognostic factors in a cohort of self-declared Māori and European breast cancer patients from Christchurch, New Zealand. Methods and Results Clinicopathological and survival data from 337 consecutive breast cancer patients (27 Māori, 310 European) were evaluated. Fewer tumours were high grade in Māori women than European women (p = 0.027). No significant ethnic differences were detected for node status, tumour type, tumour size, human epidermal growth factor receptor, oestrogen and progesterone receptor (ER/PR) status, or survival. In addition, tumour and serum samples from a sub-cohort of 14 Māori matched to 14 NZ European patients were analyzed by immunohistochemistry and enzyme linked immunosorbent assay for molecular prognostic factors. Significant correlations were detected between increased grade and increased levels of hypoxia inducible factor-1 (HIF-1α), glucose transporter-1 (GLUT-1), microvessel density (MVD) and cytokeratins CK5/6 (p < 0.05). High nodal status correlated with reduced carbonic anhydrase IX (CA-IX). Negative ER/PR status correlated with increased GLUT-1, CA-IX and MVD. Within the molecular factors, increased HIF-1α correlated with raised GLUT-1, MVD and CK5/6, and CK5/6 with GLUT-1 and MVD (p < 0.05). The small number of patients in this sub-cohort limited discrimination of ethnic differences. Conclusions In this Christchurch cohort of breast cancer patients, Māori women were no more likely than European women to have pathological or molecular factors predictive of poor prognosis. These data contrast with data from the North Island NZ, and suggest potential regional differences.

Abstract Background A functional vascular network is essential for the survival, growth and spread of solid tumours, making blood vessels a key target for therapeutic strategies. Combretastatin A-4 phosphate (CA-4-P) is a tubulin-depolymerising agent in Phase II clinical trials as a vascular disrupting agent. Not much is known of the molecular effect of CA-4-P under tumour conditions. The tumour microenvironment differs markedly from that in normal tissue, specifically with respect to oxygenation (hypoxia). Gene regulation under tumour conditions is governed by hypoxia inducible factor 1 (HIF-1), controlling angiogenic and metastatic pathways. Methods We investigated the effect of CA-4-P on factors of the upstream and downstream signalling pathway of HIF-1 in vitro. Results CA-4-P treatment under hypoxia tended to reduce HIF-1 accumulation in a concentration-dependent manner, an effect which was more prominent in endothelial cells than in cancer cell lines. Conversely, CA-4-P increased HIF-1 accumulation under aerobic conditions in vitro. At these concentrations of CA-4-P under aerobic conditions, nuclear factor κB was activated via the small GTPase RhoA, and expression of the HIF-1 downstream angiogenic effector gene, vascular endothelial growth factor (VEGF-A), was increased. Conclusion Our findings advance the understanding of signal transduction pathways involved in the actions of the anti-vascular agent CA-4-P.

Male subfertility or infertility is a common condition often characterized by men producing a low number of sperm with poor quality. To gain insight into this condition, we performed a quantitative proteomic analysis of semen samples obtained from infertile and fertile men. At least 6 proteins showed significant differences in regulation of alternatively spliced isoforms. To investigate this link between aberrant alternative splicing and production of poor-quality spermatozoa, we overexpressed the hnrnpH/F-orthologue Glorund (Glo) in Drosophila, which was also found to be abundant in poor quality human sperm. Transgenic animals produced low numbers of morphologically defective spermatozoa and aberrant formation of the "dense body," an organelle akin to the mammalian manchette. Furthermore, fertility trials demonstrated that transgenic flies were either completely infertile or highly subfertile. These findings suggest that dysregulation of hnrnpH/F is likely to result in the production of low-quality semen, leading to subfertility or infertility in men., Competing Interests: M.A.B has filed an international (“PCT”) patent application number PCT/AU2024/050211. All other authors declare no competing interests., (Crown Copyright © 2024 Published by Elsevier Inc.)

Hypertrophic cardiomyopathy (HCM) is a common contemporary, treatable, genetic disorder that can be compatible with normal longevity. While current medical therapies are ubiquitous, they are limited by a lack of solid evidence, are often inadequate, poorly tolerated, and do not alter the natural disease course. As such, there has long been a need for effective, evidence-based, and targeted disease-modifying therapies for HCM. In this review, we redefine HCM as a treatable condition, evaluate current strategies for therapeutic intervention, and discuss novel myosin inhibitors. The majority of patients with HCM have elevated left ventricular outflow tract gradients, which predicts worse symptoms and adverse outcomes. Conventional pharmacological therapies for symptomatic HCM can help improve symptoms but are often inadequate and poorly tolerated. Septal reduction therapies (surgical myectomy and alcohol septal ablation) can safely and effectively reduce refractory symptoms and improve outcomes in patients with obstructive HCM. However, they require expertise that is not universally available and are not without risks. Currently, available therapies do not alter the disease course or the progressive cardiac remodeling that ensues, nor subsequent heart failure and arrhythmias. This has been regarded as an unmet need in the care of HCM patients. Novel targeted pharmacotherapies, namely cardiac myosin inhibitors, have emerged to reverse key pathophysiological changes and alter disease course. Their favorable outcomes led to the early Food and Drug Administration approval of mavacamten, a first-in-class myosin modulator, changing the paradigm for the pharmacological treatment of HCM., (© 2024 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background: Traditionally, the columella can be difficult to reconstruct because of its unique contours, paucity of adjacent soft tissues, and tenuous vascularity. When local or regional tissues are unavailable, microsurgical transfer can provide a means for reconstruction. In this retrospective review, the authors report their experience with microsurgical reconstruction of the columella., Methods: Seventeen patients were enrolled in this study and divided into two groups: group 1, isolated columella defects; and group 2, defects of the columella and portions of adjacent soft tissues., Results: There were 10 patients in group 1. Their average age was 41.2 years. Average follow-up was 10.1 years. Causes of the columellar defects included trauma, complication of nasal reconstruction, and complication of rhinoplasty. The first dorsal metacarpal artery flap was used in seven cases, and the radial forearm flap was used in five. Two flap losses were salvaged with a second free flap. The average number of surgical revisions was 1.5. In group 2, there were seven patients with an average follow-up of 10.1 years. Causes of the columella defects included cocaine injury, carcinoma, and complication of rhinoplasty. The average number of surgical revisions was 3.3. The radial forearm flap was used in all cases. There were no flap losses. All 17 cases in this series were brought to a successful conclusion., Conclusions: The authors' experience shows that microsurgical reconstruction of the columella provides a reliable and aesthetic means for reconstruction. This technique avoids the facial disfigurement and visible scarring that often accompany use of local flaps. In addition, microsurgical flaps can be preformed "off site," which may provide certain advantages in selected cases., Clinical Question/level of Evidence: Therapeutic, IV., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Background Clinically relevant aortic dilatation (>40 mm) and increased cardiovascular risk are common among retired professional American-style football athletes. Among younger athletes, the effect of American-style football participation on aortic size is incompletely understood. We sought to determine changes in aortic root (AR) size and associated cardiovascular phenotypes across the collegiate career. Methods and Results This was a multicenter, longitudinal repeated-measures observational cohort study of athletes across 3 years of elite collegiate American-style football participation. A total of 247 athletes (119 [48%] Black, 126 [51%] White, 2 [1%] Latino; 91 [37%] linemen, 156 [63%] non-linemen) were enrolled as freshmen and studied at pre- and postseason year 1, postseason year 2 (N=140 athletes), and postseason year 3 (N=82 athletes). AR size was measured with transthoracic echocardiography. AR diameter increased over the study period from 31.7 (95% CI, 31.4-32.0) to 33.5 mm (95% CI, 33.1-33.8; P <0.001). No athlete developed an AR ≥40 mm. Athletes also demonstrated increased weight (cumulative mean Δ, 5.0 [95% CI, 4.1-6.0] kg, P <0.001), systolic blood pressure (cumulative mean Δ, 10.6 [95% CI, 8.0-13.2] mm Hg, P <0.001), pulse wave velocity (cumulative mean Δ, 0.43 [95% CI, 0.31-0.56] m/s, P <0.001), and left ventricular mass index (cumulative mean Δ, 21.2 [95% CI, 19.2-23.3] g/m 2 , P <0.001), and decreased E ' velocity (cumulative mean Δ, -2.4 [95%CI, -2.9 to -1.9] cm/s, P <0.001). Adjusting for height, player position, systolic blood pressure, and diastolic blood pressure, higher weight ( β =0.030, P =0.003), pulse wave velocity ( β =0.215, P =0.02), and left ventricular mass index ( β =0.032, P <0.001) and lower E ' ( β =-0.082, P =0.001) were associated with increased AR diameter. Conclusions Over the collegiate American-style football career, athletes demonstrate progressive AR dilatation associated with cardiac and vascular functional impairment. Future studies delineating aortic outcomes are necessary to determine whether AR dilation is indicative of maladaptive vascular remodeling in this population.

A novel reactor methodology was developed for chemical looping ammonia synthesis processes using microwave plasma for pre-activation of the stable dinitrogen molecule before reaching the catalyst surface. Microwave plasma-enhanced reactions benefit from higher production of activated species, modularity, quick startup, and lower voltage input than competing plasma-catalysis technologies. Simple, economical, and environmentally benign metallic iron catalysts were used in a cyclical atmospheric pressure synthesis of ammonia. Rates of up to 420.9 μmol min -1 g -1 were observed under mild nitriding conditions. Reaction studies showed that both surface-mediated and bulk-mediated reaction domains were found to exist depending on the time under plasma treatment. The associated density functional theory (DFT) calculations indicated that a higher temperature promoted more nitrogen species in the bulk of iron catalysts but the equilibrium limited the nitrogen converion to ammonia, and vice versa. Generation of vibrationally active N 2 and, N 2 + ions is associated with lower bulk nitridation temperatures and increased nitrogen contents versus thermal-only systems. Additionally, the kinetics of other transition metal chemical looping ammonia synthesis catalysts (Mn and CoMo) were evaluated by high-resolution time-on-stream kinetic analysis and optical plasma characterization. This study sheds new light on phenomena arising in transient nitrogen storage, kinetics, effect of plasma treatment, apparent activation energies, and rate-limiting reaction steps.

Herein, we compare the different experimental regimes used to induce testicular heat stress and summarise their impact on sperm production and male fertility. Irrespective of the protocol used, scrotal heat stress causes loss of sperm production. This is first seen 1-2 weeks post heat stress, peaking 4-5 weeks thereafter. The higher the temperature, or the longer the duration of heat, the more pronounced germ cell loss becomes, within extreme cases this leads to azoospermia. The second, and often underappreciated impact of testicular hyperthermia is the production of poor-quality spermatozoa. Typically, those cells that survive hyperthermia develop into morphologically abnormal and poorly motile spermatozoa. While both apoptotic and non-apoptotic pathways are known to contribute to hyperthermic germ cell loss, the mechanisms leading to formation of poor-quality sperm remain unclear. Mechanistically, it is unlikely that testicular hyperthermia affects messenger RNA (mRNA) abundance, as a comparison of four different mammalian studies shows no consistent single gene changes. Using available evidence, we propose two novel models to explain how testicular hyperthermia impairs sperm formation. Our first model suggests aberrant alternative splicing, while the second model proposes a loss of RNA repression. Importantly, neither model requires consistent changes in RNA species., (© 2022 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.)

Using semen data from 1271 ejaculates (79 different bulls, 11 different breeds) we have investigated the variability of semen quality in cattle living in sub-tropical conditions. Modelling shows definitive evidence of seasonal variation. Semen quality from the same bulls had a 90% "pass rate" for cryopreservation purposes in winter, dropping to less than 50% in summer. Notably, individual bulls could be classified as either "heat-tolerant" (produce good quality spermatozoa all year regardless of temperature) or "heat-sensitive" (only produce good quality sperm in summer). Nominal logistic regression demonstrated when temperatures reach 30.5 °C, 40% of heat-sensitive bulls fail a semen analysis 17 days later. At 34 °C, the proportion of bulls failing reached 63%. Ratifying this, the purposeful heating of bulls to 40 °C for 12 h showed that individual animals had different degrees of heat-sensitivity. Using historical temperature data, we then modelled how many days/decade bulls would be subject to heat-events. Beginning from 1939 to 1949, on average, the area in which bulls were kept recorded 19, 7 and 1 day over 38 °C, 39 °C and 40 °C respectively. This number steadily increases and of last decade (2010-2010), the numbers of days per decade over 38 °C, 39 °C and 40 °C jumped to a staggering 75, 39 and 15 respectively. These data show the urgent need to identify heat-tolerant bulls as future sires. Such variation likely explains why the veterinary bull breeding test often fails to accurately predict bull breeding potential., (© 2022. The Author(s).)

Background: Aging is accompanied by a dramatic decline in the interleukin (IL)-2 production capacity of human immune cells, thus making seniors more susceptible to a variety of age-related diseases. A common cause of impaired cytokine production in advanced age is a deficiency of the essential micronutrient zinc. Nevertheless, the molecular mechanisms underlying a zinc deficiency-induced decrease in IL-2 production have not yet been satisfactorily elucidated. Recent animal and in vitro data suggested that the transcription factor cAMP-responsive element modulator (CREM) [Formula: see text] plays a critical role in T cells´ disturbed IL-2 production in suboptimal zinc conditions. However, its role in the human aging process and the possibility of influencing this detrimental process by short-term zinc supplementation have not yet been evaluated., Results: Comparing peripheral lymphocytes of 23 young and 31 elderly subjects with either high, intermediate, or deficient zinc status, we observed zinc-dependent regulation of the IL-2 production mediated by the transcription factor CREM [Formula: see text]. For the first time in humans, we report a mutual relationship between low zinc levels, high CREM [Formula: see text] expression, subsequent impaired IL-2 production, and vice versa. Remarkably, an average of only 6 days of in vivo zinc supplementation to zinc-deficient seniors was sufficient to rapidly improve zinc status, reverse CREM [Formula: see text] overexpression, and counteract subsequent low IL-2 production rates., Conclusions: Our ex vivo and in vivo data identify zinc deficiency-mediated CREM [Formula: see text] overexpression as a key cellular mechanism underlying impaired IL-2 production in the elderly and point toward the use of zinc as a rapidly immune-enhancing add-on nutraceutical in geriatric therapy. During the aging process, there is a progressive decrease in zinc status, which in turn leads to overexpression of the transcription factor CREM[Formula: see text] in peripheral lymphocytes. CREMα is a negative regulator of the IL-2 gene, the overexpression of which dramatically limits adequate IL-2 production. This deleterious mechanism can be counteracted by short-term oral zinc administration, which can adjust IL-2 production in old, zinc-deficient individuals to a level similar to that of young adults., (© 2022. The Author(s).)

Background Ventricular-arterial (VA) coupling is defined as the ratio between arterial elastance (EA) and left ventricular elastance (ELV). VA uncoupling, as occurs in hypertensive heart disease, is associated with adverse outcomes. This study sought to determine the relationship between American football (AF)-associated hypertension and VA uncoupling. Methods and Results This was a multicenter, longitudinal, and repeated measures observational study of collegiate AF athletes across 3 years of AF participation. Of 200 freshman athletes initially enrolled, 142 (67 Black [47%]/75 White [53%], 58 linemen [41%]/84 nonlinemen [59%]) were prospectively studied with echocardiography and applanation tonometry. Primary echocardiographic VA coupling outcome measures were EA/ELV and ΔEA/ELV, with increased EA/ELV indicating VA uncoupling. Adjusting for race and player position, AF athletes demonstrated increased EA/ELV (mean [95% CI]Δ, 0.10 [0.04-0.15]; P =0.001) and systolic blood pressure (SBP) (mean [95% CI]Δ, 11.4 [8.3-14.5] mm Hg, P <0.001) over their collegiate AF careers. In combination with longitudinal VA uncoupling, hypertension prevalence (including both stage 1 and 2) increased from 54% at baseline to 77% (44% stage 2) at the end of the study period ( P <0.001). In multivariable mixed-effects linear regression analysis, higher SBP (β=0.021, P =0.02), lower E' (β=-0.010, P =0.03), and worse global longitudinal strain (β=0.036, P <0.001) were associated with higher EA/ELV. Increased SBP (ΔSBP, β=0.029, P =0.02) and worsened global longitudinal strain (Δglobal longitudinal strain, β=0.045, P <0.001) also predicted increased ΔEA/ELV. Conclusions VA uncoupling is associated with pathologically increased SBP and subclinical impairments in left ventricular systolic function in collegiate AF athletes, indicating a key mechanism underlying maladaptive cardiovascular phenotypes observed in this population. Future studies analyzing whether targeted clinical interventions improve VA coupling and health outcomes are warranted.

Nowadays, aging is understood as a dynamic and multifaceted dysregulation process that spares almost no human organ or cell. The immune system being among the most affected, it has been shown predominantly that its integrity determines the tightrope walk between the difference of escaping or suffering from age-related diseases. Next to drug-based anti-aging strategies, micronutrient intervention may represent an emerging but less radical way to slow immune aging. While a sufficient supply of a variety of micronutrients is undeniably important, adequate intake of the trace element zinc appears to tower over others in terms of reaching old age. Inconveniently, zinc deficiency prevalence among the elderly is high, which in turn contributes to increased susceptibility to infection, decreased anti-tumor immunity as well as attenuated response to vaccination. Driven by this research, this review aims to provide a comprehensive and up-to-date overview of the various rebalancing capabilities of zinc in the unbalanced immune system of the elderly. This includes an in-depth and cell type-centered discussion on the role of zinc in immunosenescence and inflammaging. We further address upcoming translational aspects e.g. how zinc deficiency promotes the flourishing of certain pathogenic taxa of the gut microbiome and how zinc supply counteracts such alterations in a manner that may contribute to longevity. In the light of the ongoing COVID-19 pandemic, we also briefly review current knowledge on the interdependency between age, zinc status, and respiratory infections. Based on two concrete examples and considering the latest findings in the field we conclude our remarks by outlining tremendous parallels between suboptimal zinc status and accelerated aging on the one hand and an optimized zinc status and successful aging on the other hand., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Many photoactivated processes involve a change in oxidation state during the reaction pathway and formation of highly reactive photoactivated species. Isolating these reactive species and studying their early-stage femtosecond to nanosecond (fs-ns) photodynamics can be challenging. Here we introduce a combined ultrafast transient absorption-spectroelectrochemistry (TA-SEC) approach using freestanding boron doped diamond (BDD) mesh electrodes, which also extends the time domain of conventional spectrochemical measurements. The BDD electrodes offer a wide solvent window, low background currents, and a tuneable mesh size which minimises light scattering from the electrode itself. Importantly, reactive intermediates are generated electrochemically, via oxidation/reduction of the starting stable species, enabling their dynamic interrogation using ultrafast TA-SEC, through which the early stages of the photoinduced relaxation mechanisms are elucidated. As a model system, we investigate the ultrafast spectroscopy of both anthraquinone-2-sulfonate (AQS) and its less stable counterpart, anthrahydroquinone-2-sulfonate (AH 2 QS). This is achieved by generating AH 2 QS in situ from AQS via electrochemical means, whilst simultaneously probing the associated early-stage photoinduced dynamical processes. Using this approach we unravel the relaxation mechanisms occurring in the first 2.5 ns, following absorption of ultraviolet radiation; for AQS as an extension to previous studies, and for the first time for AH 2 QS. AQS relaxation occurs via formation of triplet states, with some of these states interacting with the buffered solution to form a transient species within approximately 600 ps. In contrast, all AH 2 QS undergoes excited-state single proton transfer with the buffered solution, resulting in formation of ground state AHQS - within approximately 150 ps., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: The incidence and severity of civilian public mass shooting (CPMS) events continue to rise. Understanding the wounding pattern and incidence of potentially preventable death (PPD) after CPMS is key to updating prehospital response strategy., Methods: A retrospective study of autopsy reports after CPMS events identified via the Federal Bureau of Investigation CPMS database from December 1999 to December 31, 2017 was performed. Sites of injury, fatal injury, and incidence of PPD were determined independently by a multidisciplinary panel composed of trauma surgery, emergency medicine, critical care paramedicine, and forensic pathology., Results: Nineteen events including 213 victims were reviewed. Mean number of gunshot wounds per victim was 4.1. Sixty-four percent of gunshots were to the head and torso. The most common cause of death was brain injury (52%). Only 12% (26 victims) were transported to the hospital and the PPD rate was 15% (32 victims). The most commonly injured organs in those with PPD were the lung (59%) and spinal cord (24%). Only 6% of PPD victims had a gunshot to a vascular structure in an extremity., Conclusions: The PPD rate after CPMS is high and is due mostly to non-hemorrhaging chest wounds. Prehospital care strategy should focus on immediate point of wounding care by both laypersons and medical personnel, as well as rapid extrication of victims to definitive medical care., (Copyright © 2019 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Micronutrient deficiency, also known as the hidden hunger, affects over two billion people worldwide. Potato is the third most consumed food crops in the world, and is therefore a fundamental element of food security for millions of people. Increasing the amount of micronutrients in food crop could help alleviate worldwide micronutrient malnutrition. In the present study, we report on the identification of single nucleotide polymorphism (SNP) markers associated with folate, an essential micronutrient in the human diet. A high folate diploid clone Fol 1.6 from the wild potato relative Solanum boliviense (PI 597736) was crossed with a low/medium folate diploid S. tuberosum clone USW4self#3. The resulting F1 progeny was intermated to generate an F2 population, and tubers from 94 F2 individuals were harvested for folate analysis and SNP genotyping using a SolCap 12K Potato SNP array. Folate content in the progeny ranged from 304 to 2,952 ng g-1 dry weight. 6,759 high quality SNPs containing 4,174 (62%) polymorphic and 2,585 (38%) monomorphic SNPs were used to investigate marker-trait association. Association analysis was performed using two different approaches: survey SNP-trait association (SSTA) and SNP-trait association (STA). A total of 497 significant SNPs were identified, 489 by SSTA analysis and 43 by STA analysis. Markers identified by SSTA were located on all twelve chromosomes while those identified by STA were confined to chromosomes 2, 4, and 6. Eighteen of the significant SNPs were located within or in close proximity to folate metabolism-related genes. Forty two SNPs were identical between SSTA and STA analyses. These SNPs have potential to be used in marker-assisted selection for breeding high folate potato varieties.

Background: Early identification of patients with pelvic fractures at risk of severe bleeding requiring intervention is critical. We performed a multi-institutional study to test our hypothesis that pelvic fracture patterns predict the need for a pelvic hemorrhage control intervention., Methods: This prospective, observational, multicenter study enrolled patients with pelvic fracture due to blunt trauma. Inclusion criteria included shock on admission (systolic blood pressure <90 mm Hg or heart rate >120 beats/min and base deficit >5, and the ability to review pelvic imaging). Demographic data, open pelvic fracture, blood transfusion, pelvic hemorrhage control intervention (angioembolization, external fixator, pelvic packing, and/or REBOA [resuscitative balloon occlusion of the aorta]), and mortality were recorded. Pelvic fracture pattern was classified according to Young-Burgess in a blinded fashion. Predictors of pelvic hemorrhage control intervention and mortality were analyzed by univariate and multivariate regression analyses., Results: A total of 163 patients presenting in shock were enrolled from 11 Level I trauma centers. The most common pelvic fracture pattern was lateral compression I, followed by lateral compression I, and vertical shear. Of the 12 patients with an anterior-posterior compression III fracture, 10 (83%) required a pelvic hemorrhage control intervention. Factors associated with the need for pelvic fracture hemorrhage control intervention on univariate analysis included vertical shear pelvic fracture pattern, increasing age, and transfusion of blood products. Anterior-posterior compression III fracture patterns and open pelvic fracture predicted the need for pelvic hemorrhage control intervention on multivariate analysis. Overall in-hospital mortality for patients admitted in shock with pelvic fracture was 30% and did not differ based on pelvic fracture pattern on multivariate analysis., Conclusion: Blunt trauma patients admitted in shock with anterior-posterior compression III fracture patterns or patients with open pelvic fracture are at greatest risk of bleeding requiring pelvic hemorrhage control intervention., Level of Evidence: Prognostic/epidemiologic study, level III.

Background: Traumatic injury to the pancreas is rare but is associated with significant morbidity and mortality, including fistula, sepsis, and death. There are currently no practice management guidelines for the medical and surgical management of traumatic pancreatic injuries. The overall objective of this article is to provide evidence-based recommendations for the physician who is presented with traumatic injury to the pancreas., Methods: The MEDLINE database using PubMed was searched to identify English language articles published from January 1965 to December 2014 regarding adult patients with pancreatic injuries. A systematic review of the literature was performed, and the Grading of Recommendations Assessment, Development and Evaluation framework was used to formulate evidence-based recommendations., Results: Three hundred nineteen articles were identified. Of these, 52 articles underwent full text review, and 37 were selected for guideline construction., Conclusion: Patients with grade I/II injuries tend to have fewer complications; for these, we conditionally recommend nonoperative or nonresectional management. For grade III/IV injuries identified on computed tomography or at operation, we conditionally recommend pancreatic resection. We conditionally recommend against the routine use of octreotide for postoperative pancreatic fistula prophylaxis. No recommendations could be made regarding the following two topics: optimal surgical management of grade V injuries, and the need for routine splenectomy with distal pancreatectomy., Level of Evidence: Systematic review, level III.

Background: Recent guidelines from the Eastern Association for the Surgery of Trauma conditionally recommend cervical collar removal after a negative cervical computed tomography in obtunded adult blunt trauma patients. Although the rates of missed injury are extremely low, the impact of chronic care costs and litigation upon decision making remains unclear. We hypothesize that the cost-effectiveness of strategies that include additional imaging may contradict current guidelines., Methods: A cost-effectiveness analysis was performed for a base-case 40-year-old, obtunded man with a negative computed tomography. Strategies compared included adjunct imaging with cervical magnetic resonance imaging (MRI), collar maintenance for 6 weeks, or removal. Data on the probability for long-term collar complications, spine injury, imaging costs, complications associated with MRI, acute and chronic care, and litigation were obtained from published and Medicare data. Outcomes were expressed as 2014 US dollars and quality-adjusted life-years., Results: Collar removal was more effective and less costly than collar use or MRI (19.99 vs. 19.35 vs. 18.70 quality-adjusted life-years; $675,359 vs. $685,546 vs. $685,848) in the base-case analysis. When the probability of missed cervical injury was greater than 0.04 adjunct imaging with MRI dominated, however, collar removal remained cost-effective until the probability of missed injury exceeded 0.113 at which point collar removal exceeded the $50,000 threshold. Collar removal remained the most cost-effective approach until the probability of complications from collar use was reduced to less than 0.009, at which point collar maintenance became the most cost-effective strategy. Early collar removal dominates all strategies until the risk of complications from MRI positioning is reduced to 0.03 and remained cost-effective even when the probability of complication was reduced to 0., Conclusion: Early collar removal in obtunded adult blunt trauma patients appears to be the most effective and least costly strategy for cervical clearance based on the current literature available., Level of Evidence: Economic evaluation, level III; therapeutic study, level IV.

Introduction: Thoracic trauma is the second most prevalent nonintentional injury in the United States and is associated with significant morbidity. Analgesia for blunt thoracic trauma was first addressed by the Eastern Association for the Surgery of Trauma (EAST) with a practice management guideline published in 2005. Since that time, it was hypothesized that there have been advances in the analgesic management for blunt thoracic trauma. As a result, updated guidelines for this topic using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework recently adopted by EAST are presented., Methods: Five systematic reviews were conducted using multiple databases. The search retrieved articles regarding analgesia for blunt thoracic trauma from January1967 to August 2015. Critical outcomes of interest were analgesia, postoperative pulmonary complications, changes in pulmonary function tests, need for endotracheal intubation, and mortality. Important outcomes of interest examined included hospital and intensive care unit length of stay., Results: Seventy articles were identified. Of these, 28 articles were selected to construct the guidelines. The overall risk of bias for all studies was high. The majority of included studies examined epidural analgesia. Epidural analgesia was associated with lower short-term pain scores in most studies, but the quality and quantity of evidence were very low, and no firm evidence of benefit or harm was found when this modality was compared with other analgesic interventions. The quality of evidence for paravertebral block, intrapleural analgesia, multimodal analgesia, and intercostal nerve blocks was very low as assessed by GRADE. The limitations with the available literature precluded the formulation of strong recommendations by our panel., Conclusion: We propose two evidence-based recommendations regarding analgesia for patients with blunt thoracic trauma. The overall risk of bias for all studies was high. The limitations with the available literature precluded the formulation of strong recommendations by our panel. We conditionally recommend epidural analgesia and multimodal analgesia as options for patients with blunt thoracic trauma, but the overall quality of evidence supporting these modalities is low in trauma patients. These recommendations are based on very low-quality evidence but place a high value on patient preferences for analgesia. These recommendations are in contradistinction to the previously published Practice Management Guideline published by EAST.

Background/purpose: This study aims to investigate differences in imaging, procedure utilization, and clinical outcomes of severely injured adolescents treated at adult versus pediatric trauma centers., Methods: The National Trauma Data Bank was queried retrospectively for adolescents, 15-19years old, with a length of stay (LOS) >1day and Injury Severity Score (ISS) >25 treated at adult (ATC) or pediatric (PTC) Level 1 trauma centers from 2007 to 2011. Patient demographics and utilization of imaging and procedures were analyzed. Univariate and multivariate regression analysis was used to compare outcomes., Results: Of 12,861 adolescents, 51% were treated at ATC. Older age and more nonwhites were seen at ATC (p<0.01). Imaging and invasive procedures were more common at ATC (p<0.01). Shorter LOS (p=0.03) and higher home discharge rates (p<0.01) were seen at PTC. ISS and mortality did not differ. Age, race, ATC care (all p<0.01), and admission systolic blood pressure (SBP) (p=0.03) were predictors of CT utilization. ISS, SBP, and race (p<0.01) were risk factors for overall mortality; SBP (p=0.03) and ISS (p<0.01) predicted death from penetrating injury., Conclusions: Severely injured adolescents experience improved outcomes and decreased imaging and invasive procedures without additional mortality risk when treated at PTC. PTC is an appropriate destination for severely injured adolescents., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: There is no consensus as to the optimal treatment paradigm for patients presenting with hemorrhage from severe pelvic fracture. This study was established to determine the methods of hemorrhage control currently being used in clinical practice., Methods: This prospective, observational multi-center study enrolled patients with pelvic fracture from blunt trauma. Demographic data, admission vital signs, presence of shock on admission (systolic blood pressure < 90 mm Hg or heart rate > 120 beats per minute or base deficit < -5), method of hemorrhage control, transfusion requirements, and outcome were collected., Results: A total of 1,339 patients with pelvic fracture were enrolled from 11 Level I trauma centers. Fifty-seven percent of the patients were male, with a mean ± SD age of 47.1 ± 21.6 years, and Injury Severity Score (ISS) of 19.2 ± 12.7. In-hospital mortality was 9.0 %. Angioembolization and external fixator placement were the most common method of hemorrhage control used. A total of 128 patients (9.6%) underwent diagnostic angiography with contrast extravasation noted in 63 patients. Therapeutic angioembolization was performed on 79 patients (5.9%). There were 178 patients (13.3%) with pelvic fracture admitted in shock with a mean ± SD ISS of 28.2 ± 14.1. In the shock group, 44 patients (24.7%) underwent angiography to diagnose a pelvic source of bleeding with contrast extravasation found in 27 patients. Thirty patients (16.9%) were treated with therapeutic angioembolization. Resuscitative endovascular balloon occlusion of the aorta was performed on five patients in shock and used by only one of the participating centers. Mortality was 32.0% for patients with pelvic fracture admitted in shock., Conclusion: Patients with pelvic fracture admitted in shock have high mortality. Several methods were used for hemorrhage control with significant variation across institutions. The use of resuscitative endovascular balloon occlusion of the aorta may prove to be an important adjunct in the treatment of patients with severe pelvic fracture in shock; however, it is in the early stages of evaluation and not currently used widely across trauma centers., Level of Evidence: Prognostic study, level II; therapeutic study, level III.

Background: The management of penetrating rectal trauma invokes a complex decision tree that advocates the principles of proximal diversion (diversion) of the fecal stream, irrigation of stool from the distal rectum, and presacral drainage based on data from World War II and the Vietnam War. This guideline seeks to define the initial operative management principles for nondestructive extraperitoneal rectal injuries., Methods: A systematic review of the MEDLINE database using PubMed was performed. The search retrieved English language articles regarding penetrating rectal trauma from January 1900 to July 2014. Letters to the editor, case reports, book chapters, and review articles were excluded. Topics of investigation included the management principles of diversion, irrigation of stool from the distal rectum, and presacral drainage using the GRADE methodology., Results: A total of 306 articles were screened leading to a full-text review of 56 articles. Eighteen articles were used to formulate the recommendations of this guideline., Conclusion: This guideline consists of three conditional evidence-based recommendations. First, we conditionally recommend proximal diversion for management of these injuries. Second, we conditionally recommend the avoidance of routine presacral drains and distal rectal washout in the management of these injuries.

Introduction: Delirium is a fluctuating disturbance in consciousness associated with increased mortality. Injured warriors represent a unique unstudied population. We hypothesized delirium is common because of high injury severity scores and multidrug sedation regimens., Methods: Mandatory delirium screening using the confusion assessment method (CAM) was initiated at Craig Joint Theater Hospital in Bagram, Afghanistan. Data were collected in July to August 2012 from the first 50 English-speaking trauma patients with CAM for the Intensive Care Unit (ICU) scores., Results: Patients were male with mean age of 27.8 years; 88% of them were U.S. military personnel. Injury mechanisms were blast (68%) and gunshot (26%). Mean injury severity score was 20. Average ICU length of stay was 2.3 days; 64% were ventilated (for mean 1.2 days). Average time from arrival to CAM assessment was 7 hours, and 26 hours from the time of injury. Of patients, 44% were delirious, 36% at first CAM assessment. Fentanyl (62%) and ketamine (16%) were used for pain control (62%) and propofol for sedation (52%). There was no relationship between delirium and mechanism (p = 0.5) or ketamine on first ICU day (p = 0.2262). Delirium increased with vent days (p < .0001) and was associated with admission and mechanical ventilation (p = 0.0025)., Conclusions: This study demonstrates a high rate of delirium in this unique population., (Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.)

Background: Optimal airway management following repair of cervical tracheal injuries is unknown. This study aimed to determine the optimal airway strategy following cervical tracheal injury repair., Methods: Patients with cervical tracheal injuries admitted from January 2000 to January 2014 at seven US Level I trauma centers were identified. Patients were grouped depending on postoperative airway management: immediate or early extubation (≤24 hours, EXT), prolonged intubation (>24 hours, INT), and immediate tracheostomy (TRACH). Following univariate analysis, a multivariate model was then developed to evaluate for surgical site infection (SSI) and intensive care unit-free and ventilator-free days, comparing INT and TRACH with EXT as the reference., Results: A total of 120 cervical tracheal injuries were treated at seven Level I trauma centers. Ten patients were excluded for incomplete data, and seven died within 24 hours of admission, leaving 103 patients included in the study. Patients were grouped based on airway management: 40 (39%) in the EXT, 30 (29%) in the INT, and 33 (32%) in the TRACH group. There were no differences in demographics or injury mechanism. The INT and TRACH groups were more severely injured than the EXT group (median Injury Severity Score [ISS]: INT, 25; TRACH, 17 vs. EXT, 16; p < 0.01). Despite a higher SSI rate (TRACH, 21% vs. INT, 13% vs. EXT, 2%; p = 0.11), the TRACH group had a lower mortality rate (TRACH, 0% vs. INT, 13% vs. EXT, 0%, p < 0.01) and more ventilator-free days compared with the INT cohort. On multivariate analysis, tracheostomy was associated with an increased risk in the odds of SSI (odds ratio, 9.56; 95% confidence interval, 1.35-67.95) compared with both EXT and INT, while INT was associated with fewer ventilator-free days (correlation coefficient, -9.24; 95% confidence interval, -12.30 to -6.18) compared with both EXT and TRACH., Conclusion: In patients with a cervical tracheal injury, immediate or early extubation was common and safe. However, among those with more severe injuries, immediate tracheostomy versus prolonged intubation presents a risk-benefit decision. Immediate tracheostomy is associated with increased risk of SSI, while prolonged intubation is associated with higher risk of mortality and fewer ventilator-free days., Level of Evidence: Therapeutic study, level IV.

Background: The relationship between the prehospital airway device used and later development of ventilator-associated pneumonia (VAP) is unknown. We sought to determine if the prehospital airway device choice is associated with an increased risk of VAP in risk-adjusted critically injured patients., Methods: We performed a retrospective analysis of all trauma patients requiring definitive airway placement before intensive care unit admission at a Level I trauma center from 2008 to 2012. Prehospital airway management strategies were classified as extraglottic device placement, endotracheal intubation, bag-valve mask ventilation (BVM), or lack of a prehospital airway with subsequent intubation at the trauma center. Patients were excluded if they were hospital transfers, were dead on arrival, died in the emergency department, or did not require at least 48 hours of mechanical ventilation. The primary end point was the development of VAP as determined by institutional guidelines for diagnosis. Logistic regression was used to determine risk factors for VAP., Results: A total of 317 patients met inclusion criteria. The median age was 37 years (interquartile range, 25-51 years), 75% were male, 78% sustained a blunt injury, and the median Injury Severity Score (ISS) was 29 (interquartile range, 21-34). Ninety-seven patients (30.6%) developed VAP. Prehospital airway strategies were as follows: 17 (5.4%) had extraglottic device placement, 28 (8.8%) had BVM, 84 (26.5%) had endotracheal intubation, and 188 (59.3%) had no prehospital airway placement and were intubated after arrival. The type of prehospital airway was not statistically significant in terms of VAP development (range, 26.1-42.9%; p = 0.15). The only statistically significant predictor of VAP was length of mechanical ventilation (univariate: odds ratio, 1.14; 95% confidence interval, 1.10-1.18; p ≤ 0.01; multivariate: odds ratio, 1.15; 95% confidence interval, 1.10-1.20; p ≤ 0.01)., Conclusion: Our data suggest that the prehospital airway device used was not associated with the development of VAP., Level of Evidence: Therapeutic study, level IV; epidemiologic study, level III.

Malnutrition is one of the world's largest health concerns. Folate (also known as vitamin B₉) is essential in the human diet, and without adequate folate intake, several serious health concerns, such as congenital birth defects and an increased risk of stroke and heart disease, can occur. Most people's folate intake remains sub-optimal, even in countries that have a folic acid food fortification program in place. Staple crops, such as potatoes, represent an appropriate organism for biofortification through traditional breeding based on their worldwide consumption and the fact that modern cultivars only contain about 6% of the daily recommended intake of folate. To start breeding potatoes with enhanced folate content, high folate potato material must be identified. In this study, 250 individual plants from 77 accessions and 10 Solanum species were screened for their folate content using a tri-enzyme extraction and microbial assay. There was a 10-fold range of folate concentrations among individuals. Certain individuals within the species Solanum tuberosum subsp. andigenum, Solanum vernei and Solanum boliviense have the potential to produce more than double the folate concentrations of commercial cultivars, such as Russet Burbank. Our results show that tapping into the genetic diversity of potato is a promising approach to increase the folate content of this important crop.

Background: Reports documenting the use of extracorporeal membrane oxygenation (ECMO) after blunt thoracic trauma are scarce. We used a large, multicenter database to examine outcomes when ECMO was used in treating patients with blunt thoracic trauma., Methods: We performed a retrospective analysis of ECMO patients in the Extracorporeal Life Support Organization database between 1998 and 2014. The diagnostic code for blunt pulmonary contusion (861.21, DRG International Classification of Diseases-9th Rev.) was used to identify patients treated with ECMO after blunt thoracic trauma. Variations of pre-ECMO respiratory support were also evaluated. The primary outcome was survival to discharge; the secondary outcome was hemorrhagic complication associated with ECMO., Results: Eighty-five patients met inclusion criteria. The mean ± SEM age of the cohort was 28.9 ± 1.1 years; 71 (83.5%) were male. The mean ± SEM pre-ECMO PaO2/FIO2 ratio was 59.7 ± 3.5, and the mean ± SEM pre-ECMO length of ventilation was 94.7 ± 13.2 hours. Pre-ECMO support included inhaled nitric oxide (15 patients, 17.6%), high-frequency oscillation (10, 11.8%), and vasopressor agents (57, 67.1%). The mean ± SEM duration of ECMO was 207.4 ± 23.8 hours, and 63 patients (74.1%) were treated with venovenous ECMO. Thirty-two patients (37.6%) underwent invasive procedures before ECMO, and 12 patients (14.1%) underwent invasive procedures while on ECMO. Hemorrhagic complications occurred in 25 cases (29.4%), including 12 patients (14.1%) with surgical site bleeding and 16 (18.8%) with cannula site bleeding (6 patients had both). The rate of survival to discharge was 74.1%. Multivariate analysis showed that shorter duration of ECMO and the use of venovenous ECMO predicted survival., Conclusion: Outcomes after the use of ECMO in blunt thoracic trauma can be favorable. Some trauma patients are appropriate candidates for this therapy. Further study may discern which subpopulations of trauma patients will benefit most from ECMO., Level of Evidence: Therapeutic/care management study, level V.

Objectives: To determine the safety and efficacy of cryopreserved packed red blood cell (CPRBC) transfusion in trauma patients., Background: Liquid packed red blood cells (LPRBCs) have an abbreviated shelf-life and worsening storage lesion with age. CPRBCs are frozen 2 to 6 days after donation, stored up to 10 years, and are available for 14 days after thawing and washing. CPRBCs can be utilized in diverse settings, but the effect on clinical outcomes is unknown., Methods: We performed a prospective, randomized, double-blind study at 5 level 1 trauma centers. Stable trauma patients requiring transfusion were randomized to young LPRBCs (≤14 storage days), old LPRBCs (>14 storage days), or CPRBCs. Tissue oxygenation (StO2), biochemical and inflammatory mediators were measured, and clinical outcomes were determined., Results: Two hundred fifty-six patients with well-matched injury severity and demographics (P > 0.2) were randomized (84 young, 86 old, and 86 CPRBCs). Pretransfusion and final hematocrits were similar (P > 0.68). Patients in all groups received the same number of units postrandomization (2 [1-4]; P > 0.05). There was no difference in the change in tissue oxygenation between groups. CPRBCs contained less α2-macrogobulin, haptoglobin, C-reactive protein, and serum amyloid P (P < 0.001). Organ failure, infection rate, and mortality did not differ between groups (P > 0.2)., Conclusions: Transfusion of CPRBCs is as safe and effective as transfusion of young and old LPRBCs and provides a mechanism to deliver PRBCs in a wide variety of settings.

Background: Closed-loop controllers (CLCs) embedded within portable mechanical ventilators may allow for autonomous weaning. The ability of CLCs to maintain adequate oxygenation in the setting of hemorrhage and lung injury is unknown. We hypothesized that a portable ventilator with a CLC for inspired fraction of oxygen (FIO2) could provide oxygenation in a porcine model of hemorrhage and lung injury., Methods: Female pigs randomized to the study group (n = 6) underwent a pressure-controlled bleed (mean arterial pressure = 40 mm Hg for 30 minutes). Acute lung injury was induced by saline lung lavage followed by intentional infliction of barotrauma. Sham pigs (n = 6) underwent placement of monitoring devices without hemorrhage or lung injury. All pigs were then placed on a portable ventilator modified with a CLC algorithm, which uses feedback from pulse oximetry (SpO2) and FIO2 trends to adjust FIO2 and maintain a target SpO2 of 94% (2%). The initial FIO2 was set at 0.60. Tidal volume, positive end-expiratory pressure, rate, and inspiratory-to-expiratory ratio were constant unless changes were required clinically., Results: Study pigs had lower mean arterial pressures than shams at all time points except baseline. PaO2/FIO2 ratios were less than 300 and significantly lower than both baseline values and corresponding sham values at all time points. The CLC weaned the FIO2 at a reduced rate in study pigs relative to shams with a final mean FIO2 of 0.54 and 0.29 in study and sham pigs, respectively (p < 0.05). There was a significant divergence in the study and sham FIO2 curves but no significant difference in oxygen saturation or hypoxemia., Conclusion: Adequate oxygenation can be maintained in the setting of hemorrhage and lung injury using a portable ventilator embedded with a CLC of FIO2 based on pulse oximetry. These devices may be valuable for providing advanced medical care in resource-limited environments.

Background: Rapid assessment and treatment of coagulopathy reduces postinjury morbidity and mortality. Although thrombelastography (TEG) may be more accurate and efficient than conventional coagulation tests, it requires significant financial and personnel investments. We hypothesized that point-of-care international normalized ratio (POC INR) may provide a rapid and accurate alternative to TEG., Methods: A retrospective review of sequential trauma patients who underwent both POC INR and rapid TEG (r-TEG) testing upon presentation to a Level I trauma center from July 2012 to December 2013 was performed. POC INR was compared with r-TEG values (R value, K time, α angle, maximum amplitude, percent clot lysis in 30 minutes) and transfusion requirements. Vital signs, admission laboratory values, and injury severity were analyzed. POC INR and venous blood gas testing was performed in the emergency department. All results and Pearson correlations noted were significant if p < 0.05., Results: We identified 628 trauma patients with concomitant r-TEG and POC INR testing. Median Injury Severity Score (ISS) was 13, 20% arrived in shock (base value < -5), 21% were transfused, and 11% died. POC INR correlated with all r-TEG values, with stronger correlations for patients in shock. POC INR and r-TEG had similar correlations with blood products transfused at 4 hours and 24 hours, but only POC INR predicted substantial bleeding and massive transfusion. POC INR also correlated strongly with standard INR testing. POC INR test duration was less than 1 minute, compared with at least 30 minutes for r-TEG. Total cohort charges for POC INR were estimated at $21,980 versus $396,896 for r-TEG., Conclusion: POC INR testing is faster and cheaper than r-TEG. In addition, POC INR correlates not only with r-TEG values but also with acute blood product transfusions. POC INR provides a practical alternative for rapid coagulopathy assessment in the trauma patient at institutions that lack TEG capability., Level of Evidence: Diagnostic study, level III. Therapeutic/care management study, level IV.

Speckle-tracking left ventricular global longitudinal strain (GLS) assessment may provide substantial prognostic information for hypertrophic cardiomyopathy (HCM) patients. Reference values for GLS have been recently published. We aimed to evaluate the prognostic value of standardized reference values for GLS in HCM patients. An analysis of HCM clinic patients who underwent GLS was performed. GLS was defined as normal (more negative or equal to -16%) and abnormal (less negative than -16%) based on recently published reference values. Patients were followed for a composite of events including heart failure hospitalization, sustained ventricular arrhythmia, and all-cause death. The power of GLS to predict outcomes was assessed relative to traditional clinical and echocardiographic variables present in HCM. 79 HCM patients were followed for a median of 22 months (interquartile range 9-30 months) after imaging. During follow-up, 15 patients (19%) met the primary outcome. Abnormal GLS was the only echocardiographic variable independently predictive of the primary outcome [multivariate Hazard ratio 5.05 (95% confidence interval 1.09-23.4, p = 0.038)]. When combined with traditional clinical variables, abnormal GLS remained independently predictive of the primary outcome [multivariate Hazard ratio 5.31 (95 % confidence interval 1.18-24, p = 0.030)]. In a model including the strongest clinical and echocardiographic predictors of the primary outcome, abnormal GLS demonstrated significant incremental benefit for risk stratification [net reclassification improvement 0.75 (95 % confidence interval 0.21-1.23, p < 0.0001)]. Abnormal GLS is an independent predictor of adverse outcomes in HCM patients. Standardized use of GLS may provide significant incremental value over traditional variables for risk stratification.

Supracristal ventricular septal defect (SCVSD), a defect of the infundibular portion of the interventricular septum just below the right aortic cusp, occurs more frequently in Eastern Asian populations. SCVSD may be complicated by right sinus of Valsalva aneurysm (SoVA). We present the case of a 26-year-old male of Korean descent with a history of a childhood murmur who was referred to our institution for progressive heart failure symptoms. He was diagnosed with SCVSD and ruptured right SoVA based on history, physical exam, and echocardiography including three-dimensional transesophageal echocardiography with reconstructed surgical views. The patient underwent SCVSD closure, SoVA excision, and valve-sparing aortic root replacement. We reviewed the echocardiography literature regarding SCVSD and SoVA, and analyzed contemporary literature of SoVA and its relationship with SCVSD. We conclude that a higher prevalence of ruptured SoVA in Eastern Asians is likely related to a higher prevalence of underlying SCVSD in this population., (© 2014, Wiley Periodicals, Inc.)

Importance: Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials., Objective: To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio., Design, Setting, and Participants: Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013., Interventions: Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled)., Main Outcomes and Measures: Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status., Results: No significant differences were detected in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2 group; difference, -4.2% [95% CI, -9.6% to 1.1%]; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, -3.7% [95% CI, -10.2% to 2.7%]; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6% in 1:1:2 group; difference, -5.4% [95% CI, -10.4% to -0.5%]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P < .001) and platelets (12 U vs 6 U, P < .001) and similar amounts of red blood cells (9 U) over the first 24 hours, no differences between the 2 groups were found for the 23 prespecified complications, including acute respiratory distress syndrome, multiple organ failure, venous thromboembolism, sepsis, and transfusion-related complications., Conclusions and Relevance: Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups., Trial Registration: clinicaltrials.gov Identifier: NCT01545232.

Introduction: Group AB plasma, the traditional universal donor plasma product, is a limited resource. We compared outcomes of Group A plasma transfusion in comparison to AB., Methods: Analysis of blunt-injured patients who received emergency release plasma from was performed. Multivariable logistic regression was utilized to identify associations with morbidity and mortality., Results: There were 191 patients; 115 Group A and 76 Group AB. No differences were seen in age, sex, plasma transfusions, uncrossmatched red blood cells (RBCs), and Glasgow Coma Scale (GCS). Patients who received Group A plasma had significantly lower Injury Severity Score, chest Abbreviated Injury Scale (AIS), and scene transfer rate but not head AIS, or abdomen AIS. In addition, significant differences were noted in terms of blood products transfused within 24 hours in those receiving Group A over AB. Development of acute respiratory distress syndrome (ARDS), but not mortality, was higher within the AB cohort. No hemolytic or transfusion associated-ARDS reactions were noted in either group. ARDS; RBC transfusion volumes and head AIS were independently associated with mortality., Conclusion: Utilization of Group A plasma for emergency blood resuscitation is a safe option which may alleviate potential shortages of AB plasma., (© 2014 Wiley Periodicals, Inc.)

Although hypertension is common in American-style football (ASF) players, the presence of concomitant vascular dysfunction has not been previously characterized. We sought to examine the impact of ASF participation on arterial stiffness and to compare metrics of arterial function between collegiate ASF participants and nonathletic collegiate controls. Newly matriculated collegiate athletes were studied longitudinally during a single season of ASF participation and were then compared with healthy undergraduate controls. Arterial stiffness was characterized using applanation tonometry (SphygmoCor). ASF participants (n = 32, 18.4 ± 0.5 years) were evenly comprised of Caucasians (n = 14, 44%) and African-Americans (n = 18, 56%). A single season of ASF participation led to an increase in central aortic pulse pressure (27 ± 4 vs 34 ± 8 mm Hg, p <0.001). Relative to controls (n = 47), pulse wave velocity was increased in ASF participants (5.6 ± 0.7 vs 6.2 ± 0.9 m/s, p = 0.002). After adjusting for height, weight, body mass index, systolic blood pressure, and diastolic blood pressure, ASF participation was independently predictive of increased pulse wave velocity (β = 0.33, p = 0.04). In conclusion, ASF participation leads to changes in central hemodynamics and increased arterial stiffness., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Charge and payment discrepancies exist between hospitals, although such variation is understood incompletely. We hypothesized that hospital characteristics may account for such differences., Methods: The 2011 Medicare Inpatient Prospective Payment System for Ohio hospitals was queried for discharge diagnoses of gastrointestinal bleed (GIB), GI obstruction (GIO), and laparoscopic cholecystectomy (LC). Analyses were performed to assess the association of hospital variables with charges and payments., Results: For all three diagnoses, urban hospitals had greater median charges than rural hospitals; payments were not significantly different. Consequently, urban centers had lesser cost to charge ratios than rural centers for GIB, GIO, and LC: 0.29 versus 0.32 (P = .004), 0.27 versus 0.47 (P = .0007), and 0.26 versus 0.40 (P = .04), respectively. Centers with the greatest bed size had higher median charges and payments. Other discrepancies for all three diagnoses were greater payments at verified Level 1 centers and major teaching institutions (P value range <.0001 to .03). On multivariate analysis, excess charges were greater at urban centers for both GIB ($4,482, P = .02) and GIO ($5,700, P < .01)., Conclusion: Hospital characteristics are associated with differences in charges and payments for acute care surgery diagnoses. Further study should investigate whether these cost discrepancies are associated with outcomes., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The optimal treatment facility for adolescent trauma patients is controversial. We sought to investigate risk-adjusted outcomes of adolescents treated at adult-only trauma centers (ATCs) versus pediatric-only trauma centers (PTCs) in a state system with legislated American College of Surgeons-verified institutions to determine ideal prehospital referral patterns., Methods: The Ohio Trauma Registry was queried for patients 15 years to 19 years with a length of stay (LOS) greater than 1 day at ATC (Level 1) or PTC (Levels 1 and 2) from 2008 to 2012. Race, sex, emergency department vital signs, Injury Severity Score (ISS), computed tomography, and ultrasound imaging were reviewed. Outcomes by mechanism of injury included ventilator days, intensive care unit LOS, hospital LOS, and mortality. Statistical analysis was performed using χ test, t test, and Wilcoxon rank-sum test. Propensity score-based risk adjustment matching was used to compare groups (propensity score within 0.01, ISS within 5)., Results: Of 5,793 adolescents examined, (84% blunt, 16% penetrating) 66% were treated at an ATC. In unmatched comparisons, age, ISS, vital signs, and mortality differed significantly between centers (p < 0.01). For adolescents with blunt injury, more males (71.6% vs. 66.3%, p < 0.01) and nonwhites (19.2% vs. 15.8%, p < 0.01) were seen at PTCs. For penetrating trauma, more males (88.6% vs. 50.8%, p < 0.01) and nonwhites (66.4% vs. 34.3%, p < 0.01) were admitted to ATCs. In 873 propensity-matched pairs for blunt trauma and 95 propensity-matched pairs of penetrating injuries, no differences were seen in a priori outcomes. Imaging (blunt, head computed tomography and abdominal ultrasound, p < 0.01; penetrating, abdominal ultrasound, p = 0.02) was more common at ATCs., Conclusion: Major outcome differences for injured adolescents do not exist between ATCs and PTCs, regardless of injury pattern. Imaging remains more prevalent at ATCs. In a state system with mandatory American College of Surgeons-verified centers, injury patterns need not dictate triage decisions for adolescents., Level of Evidence: Epidemiologic study, level III.

Background: Low anti-factor Xa (anti-Xa) concentrations with twice-daily enoxaparin are associated with venous thromboembolism (VTE) in high-risk trauma patients. Concerns have been raised with once-daily dalteparin regarding effectiveness and achievable anti-Xa concentrations. The purpose of this before-and-after study was to evaluate the effectiveness of a VTE prophylaxis protocol using anti-Xa concentrations and associated dalteparin dose adjustment in high-risk trauma patients., Methods: Adult trauma patients receiving VTE chemoprophylaxis and hospitalized for at least 3 days were prospectively followed during two 6-month epochs before (PRE) and after (POST) implementation of anti-Xa monitoring. In both groups, high-risk patients received dalteparin 5,000 U subcutaneously once daily; low-risk patients received subcutaneous unfractionated heparin. High-risk POST patients with anti-Xa less than 0.1 IU/mL 12 hours after initial dalteparin dose received dalteparin every 12 hours. All patients underwent routine VTE ultrasound surveillance of the lower extremities. The primary outcome was incidence of VTE., Results: A total of 785 patients (PRE, n = 428; POST, n = 357) were included. Demographics, injury patterns, Injury Severity Score (ISS), red blood cell transfusions, intensive care unit and hospital stays, and mortality did not differ between groups. Overall, POST patients had lower VTE (7.0% vs. 13%, p = 0.009) including acute VTE (6.4% vs. 12%, p = 0.01) and proximal deep vein thromboembolism (2.2% vs. 5.7%, p = 0.019). Between high-risk patients, VTE occurred in 53 (16.3%) PRE compared with 24 (9.0%) POST patients (p = 0.01); there was no difference in VTE between low-risk patients (PRE, 2.0% vs. POST, 1.1%; p = 0.86). Among 190 high-risk POST patients with anti-Xa, 97 (51%) were less than 0.1 IU/mL. Patients with low anti-Xa had higher rates of VTE (14.0% vs. 5.4%, p = 0.05) and deep vein thromboembolism (14.4% vs. 3.2%, p = 0.01). Younger age (odds ratio, 0.97; 95% confidence interval, 0.95-0.99) and greater weight (odds ratio, 1.02; 95% confidence interval, 1.00-1.03) predicted low anti-Xa on multivariate regression., Conclusion: A VTE prophylaxis protocol using anti-Xa-based dalteparin dosage adjustment in high-risk trauma patients was associated with decreased VTE. Once-daily dalteparin 12-hour anti-Xa concentrations are suboptimal in a majority of patients and associated with VTE., Level of Evidence: Therapeutic study, level IV.

Background: Prolonged mechanical ventilation, longer hospital stay, and a lower rate of home discharge have been reported with patient-ventilator asynchrony in medical patients. Though commonly encountered, asynchrony is poorly defined within the traumatically injured population., Methods: Mechanically ventilated trauma patients at an urban, level-1 center were enrolled. Breath waveforms were recorded over 30 min within the first 48 hours following intubation. Asynchronous breaths were defined as ineffective patient triggering, double-triggering, short-cycle breaths, and long-cycle breaths. Asynchronous subjects were defined as having asynchrony in ≥ 10% of total breaths. Demographic, injury, sedation/delirium scores, and clinical and discharge outcomes were prospectively collected., Results: We enrolled 35 subjects: median age 47 y, 77.1% male, 28.6% with penetrating injuries, 16% with a history of COPD, median (IQR) Injury Severity Score 22 (17-27), and median (IQR) chest Abbreviated Injury Scale score 2 (0-6). We analyzed 15,445 breaths. Asynchrony was present in 25.7% of the subjects. No statistical differences between the asynchronous and non-asynchronous subjects were found for age, sex, injury mechanism, COPD history, delirium/sedation scores, PaO2/FIO2, PEEP, blood gas values, or sedative, narcotic, or haloperidol use. Asynchronous subjects more commonly used synchronized intermittent mandatory ventilation (SIMV) (100% vs. 38.5%, P = .002) and took fewer median spontaneous breaths/min: 4 breaths/min (IQR 3-8 breaths/min) vs. 12 breaths/min (IQR 9-14 breaths/min) (P = .007). SIMV with set breathing frequencies of ≥ 10 breaths/min was associated with increased asynchrony rates (85.7% vs. 14.3%, P = .02). We found no difference in ventilator days, ICU or hospital stay, percent discharged home, or mortality between the asynchronous and non-asynchronous subjects., Conclusions: Ventilator asynchrony is common in trauma patients. It may be associated with SIMV with a set breathing frequency of ≥ 10 breaths/min, though not with longer mechanical ventilation, longer stay, or discharge disposition. (ClinicalTrials.gov NCT01049958).

Objective: To describe and analyze the development and psychometric properties of subjective sedation scales developed for critically ill adult patients., Data Sources: PubMed, MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, Scopus, ISI Web of Science, and the International Pharmaceutical Abstracts., Study Selection: English-only publications through December 2012 with at least 30 patients older than 18 years, which included the key words of adult, critically ill, subjective sedation scale, sedation scale, validity, and reliability., Data Extraction: Two independent reviewers evaluated the psychometric properties using a standardized sedation scale psychometric scoring system., Data Synthesis: Among the 19,000+ citations extracted for the 2013 Society of Critical Care Medicine's Clinical Practice Guidelines for the Management of Pain, Agitation and Delirium and from December 2010 to 2012, 36 articles were identified compassing 11 sedation scales. The scale development process, psychometric properties, feasibility, and implementation of sedation scales were analyzed using a 0-20 scoring system. Two scales demonstrated scores indicating "very good" published psychometric properties: Richmond Agitation-Sedation Scale (19.5) and the Sedation-Agitation Scale (19). Scores with "moderate" properties include the Vancouver Interaction and Calmness Scale (14.3), Adaptation to the Intensive Care Environment (13.7), Ramsay Sedation Scale (13.2), Minnesota Sedation Assessment Tool (13), and the Nursing Instrument for the Communication of Sedation (12.8). Scales with "low" properties included the Motor Activity Assessment Scale (11.5) and the Sedation Intensive Care Score (10.5). The New Sheffield Sedation Scale (8.5) and the Observer's Assessment of Alertness/Sedation Scale (3.7) demonstrated "very low" published properties., Conclusions: Based on the current literature, and using a predetermined psychometric scoring system, the Richmond Agitation-Sedation Scale and the Sedation-Agitation Scale are the most valid and reliable subjective sedation scales for use in critically ill adult patients.

Background: Recent military experience supports a paradigm shift in shock resuscitation to damage-control resuscitation (DCR), which emphasizes a plasma-rich and crystalloid-poor approach to resuscitation. The effect of DCR on hypoxia after massive transfusion is unknown. We hypothesized that implementation of a military-derived DCR strategy in a civilian setting would lead to decreased acute hypoxia., Methods: A DCR strategy was implemented in 2007. We retrospectively reviewed patients receiving trauma surgeon operative intervention and 10 or more units of packed red blood cells (pRBCs) within 24 hours of injury at an adult Level I trauma center from 2001 to 2010. Demographic data, blood requirements, and PaO₂/FIO₂ ratios were analyzed. To evaluate evolving resuscitation strategies, we fit linear trend models to continuous variables and tested their slopes for statistical significance., Results: Two hundred sixteen patients met the study criteria, with a mean age of 35 ± 1.1 years and Injury Severity Score (ISS) of 31 ± 9.0. Of the patients, 80% were male, and 52% sustained penetrating injuries. Overall mortality was 32%. Overall mean pRBC and fresh frozen plasma (FFP) units infused in 24 hours were 23.2 ± 1.1 and 18.6 ± 1.1, respectively. Trends for patient age, sex, mechanism of injury, ISS, highest positive end-expiratory pressure, and mean total pRBC transfused over 24 hours were not statistically different from zero. An increasing trend in FFP and platelets transfused during the first 24 hours (p < 0.0001, p = 0.04, respectively) and a decrease in the pRBC/FFP ratio (p < 0.0001) were found. The amount of crystalloid infused during the initial 24 hours decreased with time (p < 0.0001). The lowest PaO₂/FIO₂ ratio recorded during the initial 24 hours increased during the study period (p = 0.01), indicating a statistically significant reduction in hypoxia., Conclusion: A military-derived DCR strategy can be implemented in the civilian setting. DCR led to significant increases in FFP transfusion, decreases in crystalloid use, and acute hypoxia.