Association of Brain Natriuretic Peptide Levels at Time of Injury with Morbidity and Mortality in Patients with Surgically Treated Hip Fractures.

An elevated brain natriuretic peptide (BNP) level has been shown to be associated with mortality and cardiac events in cardiac surgery, but its utility in the prediction of morbidity and mortality in hip fracture surgery is unknown. The primary aim of this study was to determine if there is a difference in BNP level at the time of injury between patients who do and do not develop complications after hip fracture surgery. The secondary aim was to determine if there is a predictive relationship between complications associated with the initial BNP level and mortality. Methods: A retrospective chart review of 455 hip fractures in patients ≥60 years old that were operatively treated between February 2014 and July 2018 was performed. Patients were included if they had a BNP level within 48 hours after injury (BNPi). Specific perioperative (≤7 days), 30-day, 1-year, and 2-year postoperative complications were recorded. Wilcoxon rank-sum tests were used to determine if higher BNPi values were associated with greater morbidity. The complications associated with higher BNPi values were further analyzed to assess if they were predictive of mortality, using univariate and multivariable analyses. Results: Higher BNPi was significantly associated with greater morbidity at all postoperative time points and with higher mortality at 1 and 2 years postoperatively. Furthermore, several complications including cardiac failure or exacerbation and altered mental status were associated with mortality at all time points in univariate analysis and at many time points in multivariable analysis. Conclusions: Patients with higher BNPi levels were more likely to develop complications up to 1 year postoperatively, and several of these complications were associated with increased mortality. Future studies to determine if delaying surgery until BNP levels are normalized or lowered may help guide management, and may be useful in determining the need for further medical optimization. Future studies aimed at defining a threshold BNP value at the time of injury may also help in better managing patients preoperatively. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Increasing the efficiency of randomized trial estimates via linear adjustment for a prognostic score.

Estimating causal effects from randomized experiments is central to clinical research. Reducing the statistical uncertainty in these analyses is an important objective for statisticians. Registries, prior trials, and health records constitute a growing compendium of historical data on patients under standard-of-care that may be exploitable to this end. However, most methods for historical borrowing achieve reductions in variance by sacrificing strict type-I error rate control. Here, we propose a use of historical data that exploits linear covariate adjustment to improve the efficiency of trial analyses without incurring bias. Specifically, we train a prognostic model on the historical data, then estimate the treatment effect using a linear regression while adjusting for the trial subjects' predicted outcomes (their prognostic scores). We prove that, under certain conditions, this prognostic covariate adjustment procedure attains the minimum variance possible among a large class of estimators. When those conditions are not met, prognostic covariate adjustment is still more efficient than raw covariate adjustment and the gain in efficiency is proportional to a measure of the predictive accuracy of the prognostic model above and beyond the linear relationship with the raw covariates. We demonstrate the approach using simulations and a reanalysis of an Alzheimer's disease clinical trial and observe meaningful reductions in mean-squared error and the estimated variance. Lastly, we provide a simplified formula for asymptotic variance that enables power calculations that account for these gains. Sample size reductions between 10% and 30% are attainable when using prognostic models that explain a clinically realistic percentage of the outcome variance.

Changes in Therapeutic Intensity Level Following Airway Pressure Release Ventilation in Severe Traumatic Brain Injury.

PURPOSE: Airway pressure release ventilation (APRV) utilizes high levels of airway pressure coupled with brief expiratory release to facilitate open lung ventilation. The aim of our study was to evaluate the effects of APRV-induced elevated airway pressure mean in patients with severe traumatic brain injury. MATERIALS AND METHODS: This was a retrospective cohort study at a 424-bed Level I trauma center. Linear mixed effects models were developed to assess the difference in therapeutic intensity level (TIL), intracranial pressure (ICP), and cerebral perfusion pressure (CPP) over time following the application of APRV. RESULTS: The study included 21 epochs of APRV in 21 patients. In the 6-hour epoch following the application of APRV, the TIL was significantly increased ( P = .002) and the ICP significantly decreased ( P = .041) compared to that before 6 hours. There was no significant change in CPP ( P = .42) over time. The baseline static compliance and time interaction was not significant for TIL (χ2 = 0.2 [ df 1], P = .655), CPP (χ2 = 0 [ df 1], P = 1), or ICP (χ2 = 0.1 [ df 1], P = .752). CONCLUSIONS: Application of APRV in patients with severe traumatic brain injury was associated with significantly, but not clinically meaningful, increased TIL and decreased ICP. No significant change in CPP was observed. No difference was observed based on the baseline pulmonary static compliance.

Resurgence of methamphetamine related burns and injuries: a follow-up study.

PURPOSE: Legislation enacted to curb methamphetamine production has only temporarily succeeded. Experiencing a recent increase in burns as a result of the new one-pot method, we compared methamphetamine related burn patients who utilized the previous anhydrous ammonia method of production to current patients who largely used the new one-pot method of production. BASIC PROCEDURES: Patients who were burned as a result of methamphetamine production were retrospectively reviewed. Comparisons were made including demographics, length of stay, injury severity score, hospital charges, total body surface area burned, inhalation injury, intubation, ventilator days, toxicology, fluid volumes, surgeries and complications. MAIN FINDINGS: Eighteen current study patients (88.9% male) were compared to twenty-nine (86.2% male) previous study patients. The groups were similar in age, pattern of burn injury and intubation. Total body surface area burned, injury severity score, inhalation injuries, and ventilator days were not significantly increased in the current study. Longer length of stay and greater hospital charges were incurred by the current group. Burn surgeries per patient were significantly increased in the current group. PRINCIPAL CONCLUSIONS: A new one-pot method has emerged despite legislative attempts to curtail methamphetamine production, and burns have also increased. The reason for more extensive burn surgeries in the current METH related burn patients remains enigmatic. Severity of injury and cost to society remain high.

Percutaneous tracheostomy: a new approach to the emergency airway.

BACKGROUND: Endotracheal intubation is the preferred method of airway control. Current surgical standard of care for the emergent airway when endotracheal intubation cannot be performed is cricothyroidotomy. Percutaneous tracheostomy (PT) is a widely accepted technique for elective long-term airway management in the critical care setting. We describe our experience with successful placement of PT for emergency airway control. METHODS: After institutional review board approval was obtained, patients were identified retrospectively from January 2003 to present that had emergency PT performed as identified by the DRG International Classification of Diseases--9th Rev. procedure code (31.1). Data included demographics, body mass index, admitting service, size of tracheostomy tube, reason for urgent airway access, duration PT was required, unit, time and hospital day performed, and complications. RESULTS: Eighteen patients underwent emergency PT; 61% were male, and age range was 21 years to 86 years. Indications for PT included respiratory failure associated with anaphylaxis, supraglottic edema, cardiac arrest, and blood or edema blocking the airway preventing intubation. PT was performed in various departments throughout the hospital. Admitting services included critical care intensivist (44.4%), trauma surgery (27.7%), cardiology (11.1%), medicine (11.1%), and neurology (5.5%). Most of the tracheostomy tube sizes were no. 8 (61.1%), followed by no. 7 (22.2%), no. 6 (5.5%), and no. 9 (5.5%). All PTs were successfully placed, and there were no complications. Ten of our patients had no airway in place at the time of procedure. Six patients had emergency esophageal-tracheal airways in place. Two patients had a cricothyroidotomy that was not functioning adequately. Nine patients had body mass indexes ranging from 30 kg/m² to 112 kg/m². CONCLUSION: PT provided a safe, effective emergency airway in adult patients who presented with a variety of indications, in varying locations throughout the hospital. PT performed by appropriately trained personnel may be a potential adjunct for emergent airway control in diverse settings.

Ryanodine receptor antagonism protects the ischemic liver and modulates TNF-alpha and IL-10.

BACKGROUND: Dantrolene is a ryanodine receptor and intracellular calcium antagonist. The ryanodine receptor (RyR) Ca(2+) release channel mobilizes Ca(2+) from internal stores to support a variety of cellular functions, including the inflammatory response after ischemia and reperfusion. The pharmacological mechanism of dantrolene is associated with the inhibition of the release of Ca(2+) from the skeletal muscle sarcoplasmic reticulum (SR). We hypothesized that dantrolene could exert a protective effect in our model of liver ischemia and reperfusion by modulating TNF-alpha and IL-10. MATERIAL AND METHODS: Mice subjected to 90 min of partial (70 to 80%) hepatic ischemia and 3 h of reperfusion were divided into five groups (n = 6/group): sham, ischemic control, and the dantrolene 1 mg/kg group studied at three times of administration: 15 min before reperfusion (DAN-PRE), at the time of reperfusion (DAN-RP), and 15 min after reperfusion (DAN-POS). The parameters measured at 3 h of reperfusion included serum liver function tests alanine aminotransferase (ALT) and aspartate aminotransferase (AST), TNF-alpha, and IL-10 in serum and liver histology. RESULTS: It was demonstrated that the RyR intracellular calcium antagonist dantrolene offered the most significant protection for the ischemic liver when given before reperfusion and at the time of reperfusion. AST significantly differed between the control group and the DAN-PRE and DAN-RP groups (P < 0.05). ALT showed a statistically significant decrease in the DAN-PRE treated group and a decrease, although not significant, in the DAN-RP. Histological examination demonstrated a significant decrease in vacuolization in the same both groups (P < 0.05). Necrosis was significantly diminished when dantrolene was used at the time of reperfusion; congestion decreased in the same groups but without statistical significant difference. The levels of TNF-alpha were significantly decreased in the DAN-RP group. There was a decrease in TNF-alpha in the DAN-PRE group but not statistically significant. IL-10 reflected the protection observed in necrosis and vacuolization in the histopathology with an increment at the time of reperfusion (P < 0.05). DAN-POS did not exert a protective effect in ALT, AST, liver histology, or cytokine response. CONCLUSION: For the first time the ryanodine receptor antagonist dantrolene offered significant functional and structural protection of the ischemic liver when given at the time for reperfusion and partial protection when given prereperfusion. RyR inhibition approach down-regulated the expression of TNF-alpha and induced an increment of the protective cytokine IL-10 when administered at the time of reperfusion. There was no protective effect of dantrolene after reperfusion.

The role of MAP kinases in trauma and ischemia-reperfusion.

Mitogen-activated protein kinases (MAPKs) have been the focus of a number of studies, as these compounds are involved in a number of important inflammatory cell signaling mechanisms. Recent studies have further elucidated the role of MAPKs in the inflammatory response, as a result of trauma and/or ischemia-reperfusion (I/R) injury. There are three major classes of MAPKs that may be involved in the inflammatory response: extracellular signal-regulated kinases (ERKs), stress-activated protein kinases (SAPKs)/c-Jun NH(2)-terminal kinases (JNKs), and p38 MAPKs (p38). This is clinically relevant, because these pathways may be a possible target for anti-inflammatory drug intervention. This review studies the role of MAPKs in trauma and/or I/R.

Molecular signaling pathways in ischemia/reperfusion.

Ischemia and reperfusion (I/R) is an important pathologic phenomenon that has not been completely defined from the perspective of the molecular signaling pathways developed immediately at its inception to minutes and hours thereafter. From the practical point of view, we have divided I/R into 3 phases: phase I, which occurs seconds to minutes after the injury and is associated with changes dependent on the activation of phospholipases, intracellular calcium, eicosanoids, other lipid molecules, protein kinases, inducible nitric oxide synthase, and the expression of preformed adhesion molecules like P-selectin; phase II, which occurs minutes to hours after I/R injury and is associated with the active transcription of protein synthesis of molecules like inflammatory cytokines (mainly tumor necrosis factor-alpha and interleukin 1) starting their signaling downstream from the membrane into the cytoplasm where kinases will be activated and send signals to the nucleus for the activation of transcription factors and further continuing with the inflammatory event; and phase III, which occurs several hours to days after I/R and is associated with the appearance of molecular chronic mechanisms of protection like the presence of anti-inflammatory cytokines of the IL-10 type, late adhesion molecules, and other growth factors such as TGF-beta. This completes the whole molecular event related to I/R injury.

Multiple selectin blockade with a small-molecule selectin inhibitor does not affect survival after a second inflammatory challenge with nonlethal LPS.

The effects of anti-adhesion molecule antibodies on the blockade of leukocyte-endothelial interactions have the potential of decreasing survival through possibly increased infection vulnerability. The aim of this study was to determine the effect of a small-molecule selectin inhibitor (TBC-1269) on both liver response and survival to a nonlethal lipopolysaccharide (LPS) challenge after hemorrhagic shock. Ninety-six Sprague-Dawley rats were subjected to a model of uncontrolled hemorrhagic shock. Six groups of animals were included in this study (n = 16 per group): sham/saline, sham/LPS, shock/saline, shock/LPS, shock/TBC1269, and shock/TBC-1269/LPS. Experimental design consisted of the development of hemorrhagick shock (3 mL/100 g) in a 15-min period, tail amputation and drug administration at 30 min, and subsequent resuscitation to maintain mean arterial pressure at 70mm Hg. A septic challenge was produced with 0.1 mg/kg of LPS (Escherichia coli type 78H4086; Sigma Chemical, St. Louis, MO) given intravenously via penile vein at 20 h. Liver injury tests (alanine aminotransferase, ALT), liver myeloperoxidase, liver histology, and 21-day survival were evaluated. Statistical analysis included the Bartlett test for equality of variance, a two-way analysis of variance (ANOVA), and overall followed by pairwise log-rank test for survival. Significant improvements in liver function and histology were observed in animals treated with TBC-1269 with or without a nonlethal septic challenge. Neutrophil infiltration, as evidenced by liver myeloperoxidase (MPO) was significantly decreased in animals treated with TBC-1269 alone and those having LPS administration after TBC-1269 treatment. We conclude that TBC-1269, multisectin blocker, was effective in reducing liver damage even with the addition of a second inflammatory insult as the nonlethal LPS challenge used in this study.