Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge.

Brown adipose tissue is a thermogenic organ that dissipates chemical energy as heat to protect animals against hypothermia and to counteract metabolic disease. However, the transcriptional mechanisms that determine the thermogenic capacity of brown adipose tissue before environmental cold are unknown. Here we show that histone deacetylase 3 (HDAC3) is required to activate brown adipose tissue enhancers to ensure thermogenic aptitude. Mice with brown adipose tissue-specific genetic ablation of HDAC3 become severely hypothermic and succumb to acute cold exposure. Uncoupling protein 1 (UCP1) is nearly absent in brown adipose tissue lacking HDAC3, and there is also marked downregulation of mitochondrial oxidative phosphorylation genes resulting in diminished mitochondrial respiration. Remarkably, although HDAC3 acts canonically as a transcriptional corepressor, it functions as a coactivator of oestrogen-related receptor α (ERRα) in brown adipose tissue. HDAC3 coactivation of ERRα is mediated by deacetylation of PGC-1α and is required for the transcription of Ucp1, Ppargc1a (encoding PGC-1α), and oxidative phosphorylation genes. Importantly, HDAC3 promotes the basal transcription of these genes independently of adrenergic stimulation. Thus, HDAC3 uniquely primes Ucp1 and the thermogenic transcriptional program to maintain a critical capacity for thermogenesis in brown adipose tissue that can be rapidly engaged upon exposure to dangerously cold temperature.

Using Machine Learning to Make Predictions in Patients Who Fall.

BACKGROUND: As the population ages, the incidence of traumatic falls has been increasing. We hypothesize that a machine learning algorithm can more accurately predict mortality after a fall compared with a standard logistic regression (LR) model based on immediately available admission data. Secondary objectives were to predict who would be discharged home and determine which variables had the largest effect on prediction. METHODS: All patients who were admitted for fall between 2012 and 2017 at our level 1 trauma center were reviewed. Fourteen variables describing patient demographics, injury characteristics, and physiology were collected at the time of admission and were used for prediction modeling. Algorithms assessed included LR, decision tree classifier (DTC), and random forest classifier (RFC). Area under the receiver operating characteristic curve (AUC) values were calculated for each algorithm for mortality and discharge to home. RESULTS: About 4725 patients met inclusion criteria. The mean age was 61 ± 20.5 y, Injury Severity Score 8 ± 7, length of stay 5.8 ± 7.6 d, intensive care unit length of stay 1.8± 5.2 d, and ventilator days 0.7 ± 4.2 d. The mortality rate was 3% and three times greater for elderly (aged 65 y and older) patients (5.0% versus 1.6%, P < 0.001). The AUC for predicting mortality for LR, DTC, and RFC was 0.78, 0.64, and 0.86, respectively. The AUC for predicting discharge to home for LR, DTC, and RFC was 0.72, 0.61, and 0.74, respectively. The top five variables that contribute to the prediction of mortality in descending order of importance are the Glasgow Coma Score (GCS) motor, GCS verbal, respiratory rate, GCS eye, and temperature. CONCLUSIONS: RFC can accurately predict mortality and discharge home after a fall. This predictive model can be implemented at the time of patient arrival and may help identify candidates for targeted intervention as well as improve prognostication and resource utilization.

Using State Data to Predict a Single Institution Mortality for Patients That Fall.

BACKGROUND: Falls are the most common cause of injury-related death for patients older than 45.  We hypothesized that a machine learning algorithm developed from state-level registry data could make accurate outcome predictions at a level 1 trauma hospital. METHODS: Data for all patients admitted for fall injury during 2009 - 2019 in the state of Pennsylvania were derived from the state trauma registry.  Thirteen variables that were immediately available upon patient arrival were used for prediction modeling.  Data for the test institution were withheld from model creation.  Algorithms assessed included logistic regression (LR), random forest (RF), and extreme gradient boost (XGB).  Model discrimination for mortality was assessed with area under the curve (AUC) for each algorithm at our level 1 trauma center. RESULTS: 180,284 patients met inclusion criteria.  The mean age was 69 years ± 18.5 years with a mortality rate of 4.0%.  The AUC for predicting mortality in patients that fall for LR, RF, and XGB were 0.797, 0.876, and 0.880, respectively.  The variables which contributed to the prediction in descending order of importance for XGB were respiratory rate, pulse, systolic blood pressure, ethnicity, weight, sex, age, temperature, Glasgow Coma Scale (GCS) eye, race, GCS voice, GCS motor, and blood alcohol level. CONCLUSIONS: An extreme gradient boost model developed using state-wide trauma data can accurately predict mortality after fall at a single center within the state.  This machine learning model can be implemented by local trauma systems within the state of Pennsylvania to identify patients injured by fall that require greater attention, transfer to a higher level of care, and higher resource allocation.

The projected degradation of subtropical coral assemblages by recurrent thermal stress.

Subtropical coral assemblages are threatened by similar extreme thermal stress events to their tropical counterparts. Yet, the mid- and long-term thermal stress responses of corals in subtropical environments remain largely unquantified, limiting our capacity to predict their future viability. The annual survival, growth and recruitment of 311 individual corals within the Solitary Islands Marine Park (Australia) was recorded over a 3-year period (2016-2018), including the 2015/2016 thermal stress event. These data were used to parameterise integral projection models quantifying the effect of thermal stress within a subtropical coral assemblage. Stochastic simulations were also applied to evaluate the implications of recurrent thermal stress scenarios predicted by four different Representative Concentration Pathways. We report differential shifts in population growth rates (λ) among coral populations during both stress and non-stress periods, confirming contrasting bleaching responses among taxa. However, even during non-stress periods, the observed dynamics for all taxa were unable to maintain current community composition, highlighting the need for external recruitment sources to support the community structure. Across all coral taxa, projected stochastic growth rates (λs ) were found to be lowest under higher emissions scenarios. Correspondingly, predicted increases in recurrent thermal stress regimes may accelerate the loss of coral coverage, species diversity and structural complexity within subtropical regions. We suggest that these trends are primarily due to the susceptibility of subtropical specialists and endemic species, such as Pocillopora aliciae, to thermal stress. Similarly, the viability of many tropical coral populations at higher latitudes is highly dependent on the persistence of up-current tropical systems. As such, the inherent dynamics of subtropical coral populations appear unable to support their future persistence under unprecedented thermal disturbance scenarios.

Multiple modes of Lrp4 function in modulation of Wnt/ß-catenin signaling during tooth development.

During development and homeostasis, precise control of Wnt/ß-catenin signaling is in part achieved by secreted and membrane proteins that negatively control activity of the Wnt co-receptors Lrp5 and Lrp6. Lrp4 is related to Lrp5/6 and is implicated in modulation of Wnt/ß-catenin signaling, presumably through its ability to bind to the Wise (Sostdc1)/sclerostin (Sost) family of Wnt antagonists. To gain insights into the molecular mechanisms of Lrp4 function in modulating Wnt signaling, we performed an array of genetic analyses in murine tooth development, where Lrp4 and Wise play important roles. We provide genetic evidence that Lrp4 mediates the Wnt inhibitory function of Wise and also modulates Wnt/ß-catenin signaling independently of Wise. Chimeric receptor analyses raise the possibility that the Lrp4 extracellular domain interacts with Wnt ligands, as well as the Wnt antagonists. Diverse modes of Lrp4 function are supported by severe tooth phenotypes of mice carrying a human mutation known to abolish Lrp4 binding to Sost. Our data suggest a model whereby Lrp4 modulates Wnt/ß-catenin signaling via interaction with Wnt ligands and antagonists in a context-dependent manner.

A Body of Evidence: Barriers to Family Viewing After Death by Gun Violence.

BACKGROUND: Gun violence remains a staggering public health care crisis. Although viewing the victim's body is essential to the grieving process, this practice is not universally practiced in the trauma bay and may not be supported by nurses. This study investigates how trauma nurses perceive bereavement and the potential barriers to family viewing after death by gun violence. METHODS: A survey designed to assess demographics, current practices, knowledge of policies, and personal beliefs regarding family viewing after violent crime was sent electronically to members of the Society of Trauma Nurses. Participants were asked to rank the importance of 14 viewing barriers. Descriptive analysis and perception of barriers between those who did and did not permit viewing were compared using Mann-Whitney tests. *P < 0.05 is considered significant. RESULTS: Of the 212 participants, the majority were white, female nurses (86%), aged 30 to 60 y who worked in an urban or suburban setting (58% and 30%). Only 15% had a written hospital policy with the majority not knowing if the police (68%) or medical examiner (74%) had written policies. Despite lack of guidelines, viewings did routinely occur (68%), but only 37% permitted touching. Nurses who did not permit viewing were more likely to rank legal concerns and trauma bay environment as significant barriers. CONCLUSIONS: Although family viewing after gun violence frequently occurs in the trauma bay, there are significant barriers that are compounded by lack of formal policies. Collaboration with police and medical examiners could mitigate these fears while promoting a safe and more family-centered experience.

Unplanned ICU Admission Is Associated With Worse Clinical Outcomes in Geriatric Trauma Patients.

BACKGROUND: Geriatric trauma patients who require an unplanned ICU admission (UIA) may experience worse outcomes. As such, the American College of Surgeons initiated the Trauma Quality Improvement Program which tracks UIA as a quality benchmark. We sought to determine the overall rate and impact of UIA in our geriatric trauma population and to identify predictive risk factors. METHODS: All geriatric trauma patients (≥65) admitted to an urban, level I trauma center from January 2012 to June 2018 were identified. A retrospectively collected administrative database was queried for demographics, comorbidities, injury characteristics, and outcomes. UIA were identified and medical records were queried. Univariate analysis followed by binary logistic regression analysis were performed (P < 0.05 = significant). RESULTS: Of the 2923 geriatric patients identified, 95 (3.3%) patients experienced UIA, most commonly secondary to respiratory (34.7%) and cardiac (22.1%) events. Patients with UIA were older (81 versus 78, P = 0.04), and had higher injury severity score (10 versus 9, P < 0.01) and Charlson comorbidity indices (5 versus 4, P = 0.02). On logistic regression, age (OR 1.027, P = 0.04) and injury severity score (OR 1.032, P < 0.01) were predictive of unplanned ICU admission. Of the UIA, 69.4% were readmissions, or "bounce backs". Patients initially admitted to the ICU had 2.5 increased odds of requiring UIA. Patients with UIA experienced longer hospital stays (15 versus 5, P < 0.01), more days in the ICU (6 versus 1, P < 0.01), and higher rates of mortality (11.6% versus 5.0%, P = 0.02). CONCLUSIONS: Despite relatively low injury severity, geriatric trauma patients requiring UIA have a significant increase in morbidity and mortality. Those initially admitted to the ICU are at especially high risk for UIA, suggesting the benefit of strategies to provide an extra layer of care post-ICU.

Refugia under threat: Mass bleaching of coral assemblages in high-latitude eastern Australia.

Environmental anomalies that trigger adverse physiological responses and mortality are occurring with increasing frequency due to climate change. At species' range peripheries, environmental anomalies are particularly concerning because species often exist at their environmental tolerance limits and may not be able to migrate to escape unfavourable conditions. Here, we investigated the bleaching response and mortality of 14 coral genera across high-latitude eastern Australia during a global heat stress event in 2016. We evaluated whether the severity of assemblage-scale and genus-level bleaching responses was associated with cumulative heat stress and/or local environmental history, including long-term mean temperatures during the hottest month of each year (SSTLTMAX ), and annual fluctuations in water temperature (SSTVAR ) and solar irradiance (PARZVAR ). The most severely-bleached genera included species that were either endemic to the region (Pocillopora aliciae) or rare in the tropics (e.g. Porites heronensis). Pocillopora spp., in particular, showed high rates of immediate mortality. Bleaching severity of Pocillopora was high where SSTLTMAX was low or PARZVAR was high, whereas bleaching severity of Porites was directly associated with cumulative heat stress. While many tropical Acropora species are extremely vulnerable to bleaching, the Acropora species common at high latitudes, such as A. glauca and A. solitaryensis, showed little incidence of bleaching and immediate mortality. Two other regionally-abundant genera, Goniastrea and Turbinaria, were also largely unaffected by the thermal anomaly. The severity of assemblage-scale bleaching responses was poorly explained by the environmental parameters we examined. Instead, the severity of assemblage-scale bleaching was associated with local differences in species abundance and taxon-specific bleaching responses. The marked taxonomic disparity in bleaching severity, coupled with high mortality of high-latitude endemics, point to climate-driven simplification of assemblage structures and progressive homogenisation of reef functions at these high-latitude locations.

Metabolic tracing analysis reveals substrate-specific metabolic deficits in platelet storage lesion.

BACKGROUND: Storage of platelets (PLTs) results in a progressive defect termed PLT storage lesion (PSL). The PSL is characterized by poor PLT quality on a variety of assays. Metabolic defects are thought to underlie the PSL; thus this study was designed to quantitatively probe specific metabolic pathways over PLT storage. STUDY DESIGN AND METHODS: Relative incorporation of stable isotope-labeled substrates was quantified by isotopologue analysis of key acyl-coenzyme A (CoA) thioester products for fresh, viable (after collection, Days 2-5), and expired PLTs (after Day 5). We examined the incorporation of acetate, glucose, and palmitate into acetyl- and succinyl-CoA via liquid chromatography-tandem mass spectrometry. RESULTS: Storage-related defects in the incorporation of acetyl-CoA derived from acetate and palmitate were observed. Carbon derived from palmitate and acetate in succinyl-CoA was reduced over storage time. Glucose incorporation into succinyl-CoA increased in viable PLTs and then decreased in expired PLTs. Carbon derived from octanoate and pyruvate remained partially able to incorporate into acetyl- and succinyl-CoA in expired PLTs, with high variability in pyruvate incorporation. CONCLUSION: Isotopologue analysis is useful in probing substrate specific defects in the PSL.

Quantifying Disparities in Urban Firearm Violence by Race and Place in Philadelphia, Pennsylvania: A Cartographic Study.

OBJECTIVES: To describe variability in the burden of firearm violence by race, income, and place in an urban context. METHODS: We used Philadelphia Police Department data from 2013 to 2014 to calculate firearm assault rates within census block groups for both victim residence and event locations, stratifying by race and block group income. We used cartographic modeling to determine variations in incidence of firearm assault by race, neighborhood income, and place. RESULTS: The overall rate of firearm assault was 5.0 times higher (95% confidence interval [CI] = 4.5, 5.6) for Black people compared with White people. Firearm assault rates were higher among Black people across all victim residence incomes. Relative risk of firearm assault reached 15.8 times higher (95% CI = 10.7, 23.2) for Black residents in the highest-income block groups when compared with high-income White individuals. Firearm assault events tended to occur in low-income areas and were concentrated in several "hot spot" locations with high proportions of Black residents. CONCLUSIONS: Profound disparity in exposure to firearm violence by race and place exists in Philadelphia. Black people were substantially more likely than White people to sustain firearm assault, regardless of neighborhood income.

Lrp4 and Wise interplay controls the formation and patterning of mammary and other skin appendage placodes by modulating Wnt signaling.

The future site of skin appendage development is marked by a placode during embryogenesis. Although Wnt/ß-catenin signaling is known to be essential for skin appendage development, it is unclear which cellular processes are controlled by the signaling and how the precise level of the signaling activity is achieved during placode formation. We have investigated roles for Lrp4 and its potential ligand Wise (Sostdc1) in mammary and other skin appendage placodes. Lrp4 mutant mice displayed a delay in placode initiation and changes in distribution and number of mammary precursor cells leading to abnormal morphology, number and position of mammary placodes. These Lrp4 mammary defects, as well as limb defects, were associated with elevated Wnt/ß-catenin signaling and were rescued by reducing the dose of the Wnt co-receptor genes Lrp5 and Lrp6, or by inactivating the gene encoding ß-catenin. Wise-null mice phenocopied a subset of the Lrp4 mammary defects and Wise overexpression reduced the number of mammary precursor cells. Genetic epistasis analyses suggest that Wise requires Lrp4 to exert its function and that, together, they have a role in limiting mammary fate, but Lrp4 has an early Wise-independent role in facilitating placode formation. Lrp4 and Wise mutants also share defects in vibrissa and hair follicle development, suggesting that the roles played by Lrp4 and Wise are common to skin appendages. Our study presents genetic evidence for interplay between Lrp4 and Wise in inhibiting Wnt/ß-catenin signaling and provides an insight into how modulation of Wnt/ß-catenin signaling controls cellular processes important for skin placode formation.

Essential role of mitochondrial energy metabolism in Foxp3⁺ T-regulatory cell function and allograft survival.

Conventional T (Tcon) cells and Foxp3(+) T-regulatory (Treg) cells are thought to have differing metabolic requirements, but little is known of mitochondrial functions within these cell populations in vivo. In murine studies, we found that activation of both Tcon and Treg cells led to myocyte enhancer factor 2 (Mef2)-induced expression of genes important to oxidative phosphorylation (OXPHOS). Inhibition of OXPHOS impaired both Tcon and Treg cell function compared to wild-type cells but disproportionally affected Treg cells. Deletion of Pgc1α or Sirt3, which are key regulators of OXPHOS, abrogated Treg-dependent suppressive function and impaired allograft survival. Mef2 is inhibited by histone/protein deacetylase-9 (Hdac9), and Hdac9 deletion increased Treg suppressive function. Hdac9(-/-) Treg showed increased expression of Pgc1α and Sirt3, and improved mitochondrial respiration, compared to wild-type Treg cells. Our data show that key OXPHOS regulators are required for optimal Treg function and Treg-dependent allograft acceptance. These findings provide a novel approach to increase Treg function and give insights into the fundamental mechanisms by which mitochondrial energy metabolism regulates immune cell functions in vivo.

SIRT1 downregulation in pneumonia is associated with an immature neutrophil response and increased disease severity.

BACKGROUND: Pneumonia remains a common complication in trauma patients. Sirtuin 1 (SIRT1) is an anti-inflammatory NAD + -dependent deacetylase that has been shown to reduce the severity of ARDS in polymicrobial sepsis. The impact of SIRT1 in acute pneumonia, however, remains unknown. We hypothesized that SIRT1 deletion in pneumonia would worsen the inflammatory response and clinical severity, and that increased SIRT1 expression would be protective. METHODS: Ten- to 14-week-old male and female SIRT1 knockout (S1KO) mice, SIRT1 overexpressor (S1OE) mice, and their wildtype (WT) littermates underwent intra-tracheal inoculation with Pseudomonas aeruginosa . Rectal temperature was recorded, SIRT1 lung protein was quantified by western blotting, Sirt1 mRNA was measured by qPCR, and lung leukocyte subpopulations were analyzed by flow cytometry. Data were analyzed by one-way ANOVA using Prism software. RESULTS: Pneumonia created a functional SIRT1 knockdown in the lungs of WT mice by 4 hours, resulting in comparable SIRT1 levels and temperatures to the S1KO mice by 12 hours. Pneumonia also partially reduced SIRT1expression in S1OE mice, but S1OE mice still had improved thermoregulation 12 hours after pneumonia. In all groups, Sirt1 mRNA expression was not affected by infection. Sirtuin 1 deletion was associated with decreased neutrophil infiltration in the lung, as well as a shift toward a more immature neutrophil phenotype. SIRT1 deletion was also associated with decreased myeloperoxidase-positive neutrophils in the lungs following pneumonia, indicating decreased neutrophil activity. S1OE mice had no change in lung leukocyte subpopulations when compared to WT. CONCLUSION: Pneumonia creates a functional SIRT1 knockdown in mice. SIRT1 deletion altered the early inflammatory cell response to pneumonia, resulting in a neutrophil response that would be less favorable for bacterial clearance. Despite overexpression of SIRT1, S1OE mice also developed low SIRT1 levels and exhibited only minimal improvement. This suggests increasing SIRT1 transcription is not sufficient to overcome pneumonia-induced downregulation and has implications for future treatment options. Targeting SIRT1 through increasing protein stability may promote a more efficient inflammatory cell response to pneumonia, thereby preventing subsequent lung injury.

Developing a National Trauma Research Action Plan: Results from the regulatory challenges Delphi survey.

BACKGROUND: In 2016, the National Academies of Sciences, Engineering, and Medicine issued a report calling for a National Trauma Research Action Plan (NTRAP) requiring a resourced, coordinated, joint approach to trauma care research. The National Academies of Sciences, Engineering, and Medicine report recommended the identification of regulatory barriers to trauma research. The NTRAP Regulatory Challenges Panel of trauma researchers and regulatory professionals was convened to identify the most challenging aspects of regulatory processes involved in conducting research. METHODS: Trauma researchers and regulatory experts were recruited to identify and rate challenging regulatory issues in 2021 to 2022. Challenge statements were developed from a comprehensive scoping review. Panelists rated the challenge level for each statement on a 9-point Likert scale. The Delphi survey was conducted over three online rounds. Consensus was defined a priori as ≥60% agreement. Results of the Delphi survey were presented to the panel during a webinar. Panel participants then participated in breakout sessions to strategize solutions, share lessons learned, and identify where more regulatory guidance is needed. RESULTS: Thirty-eight subject matter experts rated 175 regulatory challenges, of which 141 (81%) reached the consensus threshold. Of the consensus-reaching challenge statements, 42 had a challenge rating of 6 or higher. Among the highest-rated challenges were issues pertaining to conducting prehospital research, exception from informed consent, mistrust of research among various racial and ethnic groups, and issues specific to conducting pediatric trauma research. CONCLUSION: This Delphi survey rated challenges culled from a regulatory literature scoping review. The panel identified the most challenging aspects of human subjects protection while conducting trauma research and recommended strategies and best practices to address them. The findings from this study were used to develop the NTRAP Investigator Toolkit, which is available on the internet as a resource for trauma researchers. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Colonic injuries and the damage control abdomen: does management strategy matter?

BACKGROUND: The optimal management of colon injury patients requiring damage control laparotomy (DCL) is controversial. The objective of this study was to assess the safety of colonic resection and anastomosis versus fecal diversion in trauma patients requiring DCL. METHODS: Patients with traumatic colon injuries undergoing DCL between 2000 and 2010 were identified by the database and chart review. Those who died within 48 h were excluded. Patients were divided into two groups: those undergoing one or more colonic anastomoses with or without distal colostomy (group 1) and those undergoing colostomy only or one or more colonic anastomoses with a protecting proximal ostomy (group 2). Variables were compared using Wilcoxon rank sum, χ2, or Fisher exact tests as appropriate. RESULTS: Sixty-one patients were included (group 1, n=28 and group 2, n=33). Fascial closure rates (group 1, 50% versus group 2, 61%; P=0.45), hospital length of stay (29 versus 23 d; P=0.89), and in-patient mortality (11% versus 12%; P=1.0) were similar between groups. There were a total of 11 anastomotic leaks, five of which were related to non-colonic enteric repairs. Colonic anastomosis leak rates were 16% overall (six of the 38 patients), 14% in group 1 (four of the 28 patients), and 20% in group 2 (two of the 10 patients). Compared with patients who did not leak, patients who leaked had a higher median age (37 versus 25 y; P=0.05), greater likelihood of not achieving facial closure before post-injury day 5 (18% versus 2%; P=0.003), and a longer hospital length of stay (46 versus 25 d; P=0.003). CONCLUSIONS: Outcomes after colonic injury in the setting of DCL were similar regardless of the surgical management strategy. Based on these findings, a strategy of diversion over anastomosis cannot be strongly recommended.

Altered thyroid function in severely injured patients.

BACKGROUND: Hemorrhagic shock profoundly affects the neuroendocrine profile of trauma patients, and we hypothesized that massive resuscitation would negatively impact thyroid function. METHODS: A prospective, observational study investigating thyroid function in hypotensive trauma patients (systolic blood pressure <90 mm Hg × 2) who survived >48 h was conducted at a Level I center over a 6-mo period. Blood samples for thyroid function were collected at time of presentation to the trauma bay and serially for 48 h. Collected data included demographics, injury data, vital signs, transfusion needs, crystalloid use, and vasopressor requirements. Patients receiving >5 units packed red blood cells (PRBC) within 12 h were compared with those receiving ≤5 units. RESULTS: Patients who required >5 units of PRBC/12 h had significantly lower total and free T4 levels on initial presentation, and levels remained significantly depressed over the next 48 h when compared with patients who required a less aggressive resuscitative effort. T3 values were markedly suppressed during the initial 48 h post trauma in all patients, but were significantly lower in patients requiring >5 units PRBC. TSH levels remained within the normal range for all time points. Lower trauma admission T4 levels were associated with the need for greater crystalloid resuscitation within the first 24 h. CONCLUSION: Measurements of thyroid function are significantly altered in severely injured patients on initial presentation, and low T4 levels predict the need for large resuscitation. Further research investigating the profile and impact of thyroid function in trauma patients during resuscitation and recovery is warranted.

Mineralocorticoid deficiency in hemorrhagic shock.

BACKGROUND: In the critically ill, mineralocorticoid deficiency (MD) is associated with greater disease severity, the development of acute renal insufficiency, and increased mortality. We hypothesized that severely injured trauma patients presenting with hemorrhagic shock would demonstrate a high degree of MD. We also hypothesized that MD in these patients would be associated with increased length of stay, hypotension, fluid requirements, and acute kidney injury (AKI). MATERIALS AND METHODS: Thirty-two trauma patients in hemorrhagic shock on admission to the trauma bay (SBP <90 mm Hg × 2) were enrolled. Blood samples were obtained on ICU admission and 8, 16, 24, and 48 hours later. Plasma aldosterone (PA) and renin (PR) were assayed by radioimmunoassay. MD was defined as a ratio of PA/PR ≤2. Demographic data, injury severity score, ICU and hospital length of stay, fluid requirements, mean arterial pressure, serum sodium, hypotension, and risk for AKI were compared for patients with and without MD. RESULTS: At ICU admission, 48% of patients met criteria for MD. Patients with MD were significantly more likely to experience hypotension (MAP ≤60 mm Hg) during the study period. MD patients required significantly more units of blood in 48 h than non-MD patients (13 [7-22] versus 5 [2-7], P = 0.015) and had increased crystalloid requirements (18L [14-23] versus 9L [6-10], P < 0.001). MD patients were at higher risk for AKI according to RIFLE and AKIN criteria. CONCLUSIONS: MD is a common entity in trauma patients presenting in hemorrhagic shock. Patients with MD required a more aggressive resuscitative effort, were more likely to experience hypotension, and had a higher risk of AKI than non-MD patients. Future studies are needed to fully understand the impact of MD following trauma and the potential role for hormonal replacement therapy.

Increased platelet storage time is associated with mitochondrial dysfunction and impaired platelet function.

BACKGROUND: Hemorrhagic shock is a leading cause of death following severe trauma, and platelet transfusions are frequently necessary to achieve hemostasis. Platelets, however, require special storage conditions, and storage time has been associated with loss of platelet quality. We hypothesized that standard storage conditions have a deleterious effect on platelet mitochondrial function and platelet activation. MATERIALS AND METHODS: Platelet donations were collected from healthy donors (n = 5) and stored in gas-permeable collection bags according to American Association of Blood Bank recommendations. Platelet units were sampled from day of collection (day 0) until day 7. High-resolution respirometry was used to assess baseline mitochondrial respiration, maximal oxygen utilization, and individual mitochondrial complex-dependent respiration. Fluorescence-activated cell sorting was performed to analyze mitochondrial content, mitochondrial reactive oxygen species, the expression of P-selectin (both before and after challenge with thrombin receptor-activating peptide), and apoptosis. Data were analyzed using analysis of variance and Pearson correlation (P < 0.05 significant). RESULTS: Mitochondrial respiration decreased significantly in platelets stored longer than 2 d (P < 0.05). Platelets also demonstrated a persistent decrease in response to stimulation with thrombin receptor-activating peptide by the third day of storage (P < 0.05) as well as an increase in mitochondrial reactive oxygen species and apoptosis (P < 0.05). Mitochondrial respiration significantly correlated with platelet capacity to activate (r = 0.8, P < 0.05). CONCLUSIONS: Platelet mitochondrial respiratory function and activation response decrease significantly in platelets stored for 3 d or more. Because platelet transfusions almost universally occur between the third and fifth day of storage, our findings may have significant clinical importance and warrant further in vivo analysis.

Penetrating trauma in urban women: patterns of injury and violence.

BACKGROUND: Penetrating trauma is known to occur with less frequency in women than in men, and this difference has resulted in a lack of characterization of penetrating injury patterns involving women. We hypothesized that the nature of penetrating injury differs significantly by gender and that these injuries in women are associated with important psychosocial and environmental factors. MATERIALS AND METHODS: A level 1 urban trauma center registry was queried for all patients with penetrating injuries from 2002-2010. Patient and injury variables (demographics and mechanism of injury) were abstracted and compared between genders; additional social and psychiatric histories and perpetrator information were collected from the records of admitted female patients. RESULTS: Injured women were more likely to be Caucasian, suffer stab wounds instead of gunshot wounds, and present with a higher blood alcohol level than men. Compared with women with gunshot wounds, those with stab wounds were three times more likely to report a psychiatric or intimate partner violence history. Women with self-inflicted injuries had a significantly greater incidence of prior penetrating injury and psychiatric and criminal history. Male perpetrators outnumbered female perpetrators; patients frequently not only knew their perpetrator but also were their intimate partners. Intimate partner violence and random cross-fire incidents each accounted for about a quarter of injuries observed. CONCLUSIONS: Penetrating injuries in women represent a nonnegligible subset of injuries seen in urban trauma centers. Psychiatric and social risk factors for violence play important roles in these cases, particularly when self-infliction is suspected. Resources allocated for urban violence prevention should proportionately reflect the particular patterns of violence observed in injured women.