N-acetyl-cysteine increases cellular dysfunction in progressive chronic kidney damage after acute kidney injury by dampening endogenous antioxidant responses.

PubMed

Small, David M; Sanchez, Washington Y; Roy, Sandrine F; Morais, Christudas; Brooks, Heddwen L; Coombes, Jeff S; Johnson, David W; Gobe, Glenda C

2018-05-01

Oxidative stress and mitochondrial dysfunction exacerbate acute kidney injury (AKI), but their role in any associated progress to chronic kidney disease (CKD) remains unclear. Antioxidant therapies often benefit AKI, but their benefits in CKD are controversial since clinical and preclinical investigations often conflict. Here we examined the influence of the antioxidant N-acetyl-cysteine (NAC) on oxidative stress and mitochondrial function during AKI (20-min bilateral renal ischemia plus reperfusion/IR) and progression to chronic kidney pathologies in mice. NAC (5% in diet) was given to mice 7 days prior and up to 21 days post-IR (21d-IR). NAC treatment resulted in the following: prevented proximal tubular epithelial cell apoptosis at early IR (40-min postischemia), yet enhanced interstitial cell proliferation at 21d-IR; increased transforming growth factor-β1 expression independent of IR time; and significantly dampened nuclear factor-like 2-initiated cytoprotective signaling at early IR. In the long term, NAC enhanced cellular metabolic impairment demonstrated by increased peroxisome proliferator activator-γ serine-112 phosphorylation at 21d-IR. Intravital multiphoton microscopy revealed increased endogenous fluorescence of nicotinamide adenine dinucleotide (NADH) in cortical tubular epithelial cells during ischemia, and at 21d-IR that was not attenuated with NAC. Fluorescence lifetime imaging microscopy demonstrated persistent metabolic impairment by increased free/bound NADH in the cortex at 21d-IR that was enhanced by NAC. Increased mitochondrial dysfunction in remnant tubular cells was demonstrated at 21d-IR by tetramethylrhodamine methyl ester fluorimetry. In summary, NAC enhanced progression to CKD following AKI not only by dampening endogenous cellular antioxidant responses at time of injury but also by enhancing persistent kidney mitochondrial and metabolic dysfunction.

Young Children's Acute Stress After a Burn Injury: Disentangling the Role of Injury Severity and Parental Acute Stress.

PubMed

Haag, Ann-Christin; Landolt, Markus A

2017-09-01

Although injury severity and parental stress are strong predictors of posttraumatic adjustment in young children after burns, little is known about the interplay of these variables. This study aimed at clarifying mediation processes between injury severity and mother's, father's, and young child's acute stress. Structural equation modeling was used to examine the relationships between injury severity and parental and child acute stress. Parents of 138 burn-injured children (ages 1-4 years) completed standardized questionnaires on average 19 days postinjury. Sixteen children (11.7%) met Diagnostic and Statistical Manual of Mental Disorders, 5th edition, preschool criteria for posttraumatic stress disorder (excluding time criterion). The model revealed a significant mediation of maternal acute stress, with the effect of injury severity on a child's acute stress mediated by maternal acute stress. Paternal acute stress failed to serve as a mediating variable. Our findings confirm mothers' crucial role in the posttraumatic adjustment of young children. Clinically, mothers' acute stress should be monitored. © The Author 2017. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Reappraisal of xenobiotic-induced, oxidative stress-mediated cellular injury in chronic pancreatitis: A systematic review

PubMed Central

Siriwardena, Ajith K

2014-01-01

AIM: To reappraise the hypothesis of xenobiotic induced, cytochrome P450-mediated, micronutrient-deficient oxidative injury in chronic pancreatitis. METHODS: Individual searches of the Medline and Embase databases were conducted for each component of the theory of oxidative-stress mediated cellular injury for the period from 1st January 1990 to 31st December 2012 using appropriate medical subject headings. Boolean operators were used. The individual components were drawn from a recent update on theory of oxidative stress-mediated cellular injury in chronic pancreatitis. RESULTS: In relation to the association between exposure to volatile hydrocarbons and chronic pancreatitis the studies fail to adequately control for alcohol intake. Cytochrome P450 (CYP) induction occurs as a diffuse hepatic and extra-hepatic response to xenobiotic exposure rather than an acinar cell-specific process. GSH depletion is not consistently confirmed. There is good evidence of superoxide dismutase depletion in acute phases of injury but less to support a chronic intra-acinar depletion. Although the liver is the principal site of CYP induction there is no evidence to suggest that oxidative by-products are carried in bile and reflux into the pancreatic duct to cause injury. CONCLUSION: Pancreatic acinar cell injury due to short-lived oxygen free radicals (generated by injury mediated by prematurely activated intra-acinar trypsin) is an important mechanism of cell damage in chronic pancreatitis. However, in contemporary paradigms of chronic pancreatitis this should be seen as one of a series of cell-injury mechanisms rather than a sole mediator. PMID:24659895

Optical monitoring of spinal cord subcellular damage after acute spinal cord injury

NASA Astrophysics Data System (ADS)

Shadgan, Babak; Manouchehri, Neda; So, Kitty; Shortt, Katelyn; Fong, Allan; Streijger, Femke; Macnab, Andrew; Kwon, Brian K.

2018-02-01

Introduction: Sudden physical trauma to the spinal cord results in acute spinal cord injury (SCI), leading to spinal cord (SC) tissue destruction, acute inflammation, increased SC intraparenchymal pressure, and tissue ischemia, hypoxia, and cellular necrosis. The ability to monitor SC tissue viability at subcellular level, using a real-time noninvasive method, would be extremely valuable to clinicians for estimating acute SCI damage, and adjusting and monitoring treatment in the intensive care setting. This study examined the feasibility and sensitivity of a custommade near infrared spectroscopy (NIRS) sensor to monitor the oxidation state of SC mitochondrial cytochrome aa3 (CCO), which reflects the subcellular damage of SC tissue in an animal model of SCI. Methods: Six anesthetized Yorkshire pigs were studied using a custom-made multi-wavelength NIRS system with a miniaturized optical sensor applied directly on the surgically exposed SC at T9. The oxidation states of SC tissue hemoglobin and CCO were monitored before, during and after acute SCI, and during mean arterial pressure alterations. Results: Non-invasive NIRS monitoring reflected changes in SC tissue CCO, simultaneous but independent of changes in hemoglobin saturation following acute SCI. A consistent decrease in SC tissue CCO chromophore concentration (-1.98 +/- 2.1 ab, p<0.05) was observed following SCI, indicating progressive SC cellular damage at the injury site. Elevation of mean arterial pressure can reduce SC tissue damage as suggested by different researchers and observed by significant increase in SC tissue CCO concentration (1.51 +/- 1.7 ab, p<0.05) in this study. Conclusions: This pilot study indicates that a novel miniaturized multi-wave NIRS sensor has the potential to monitor post-SCI changes of SC cytochrome aa3 oxygenation state in real time. Further development of this method may offer new options for improved SCI care.

Serum from CCl4-induced acute rat injury model induces differentiation of ADSCs towards hepatic cells and reduces liver fibrosis.

PubMed

Baig, Maria Tayyab; Ali, Gibran; Awan, Sana Javaid; Shehzad, Umara; Mehmood, Azra; Mohsin, Sadia; Khan, Shaheen N; Riazuddin, Sheikh

2017-10-01

Cellular therapies hold promise to alleviate liver diseases. This study explored the potential of allogenic serum isolated from rat with acute CCl 4 injury to differentiate adipose derived stem cells (ADSCs) towards hepatic lineage. Acute liver injury was induced by CCl 4 which caused significant increase in serum levels of VEGF, SDF1α and EGF. ADSCs were preconditioned with 3% serum isolated from normal and acute liver injury models. ADSCs showed enhanced expression of hepatic markers (AFP, albumin, CK8 and CK19). These differentiated ADSCs were transplanted intra-hepatically in CCl 4 -induced liver fibrosis model. After one month of transplantation, fibrosis and liver functions (alkaline phosphatase, ALAT and bilirubin) showed marked improvement in acute injury group. Elevated expression of hepatic (AFP, albumin, CK 18 and HNF4a) and pro survival markers (PCNA and VEGF) and improvement in liver architecture as deduced from results of alpha smooth muscle actin, Sirius red and Masson's trichome staining was observed.

An Observational Cohort Feasibility Study to Identify Microvesicle and Micro-RNA Biomarkers of Acute Kidney Injury Following Pediatric Cardiac Surgery.

PubMed

Sullo, Nikol; Mariani, Silvia; JnTala, Maria; Kumar, Tracy; Woźniak, Marcin J; Smallwood, Dawn; Pais, Paolo; Westrope, Claire; Lotto, Attilio; Murphy, Gavin J

2018-06-15

Micro-RNA, small noncoding RNA fragments involved in gene regulation, and microvesicles, membrane-bound particles less than 1 μm known to regulate cellular processes including responses to injury, may serve as disease-specific biomarkers of acute kidney injury. We evaluated the feasibility of measuring these signals as well as other known acute kidney injury biomarkers in a mixed pediatric cardiac surgery population. Single center prospective cohort feasibility study. PICU. Twenty-four children (≤ 17 yr) undergoing cardiac surgery with cardiopulmonary bypass without preexisting inflammatory state, acute kidney injury, or extracorporeal life support. None. Acute kidney injury was defined according to modified Kidney Diseases Improving Global Outcomes criteria. Blood and urine samples were collected preoperatively and at 6-12 and 24 hours. Microvesicles derivation was assessed using flow cytometry and NanoSight analysis. Micro-RNAs were isolated from plasma and analyzed by microarray and quantitative real-time polymerase chain reaction. Data completeness for the primary outcomes was 100%. Patients with acute kidney injury (n = 14/24) were younger, underwent longer cardiopulmonary bypass, and required greater inotrope support. Acute kidney injury subjects had different fractional content of platelets and endothelial-derived microvesicles before surgery. Platelets and endothelial microvesicles levels were higher in acute kidney injury patients. A number of micro-RNA species were differentially expressed in acute kidney injury patients. Pathway analysis of candidate target genes in the kidney suggested that the most often affected pathways were phosphatase and tensin homolog and signal transducer and activator of transcription 3 signaling. Microvesicles and micro-RNAs expression patterns in pediatric cardiac surgery patients can be measured in children and potentially serve as tools for stratification of patients at risk of acute kidney injury.

[Acute injuries of lateral ankle joint ligaments].

PubMed

Lacko, M; Sidor, Z; Stolfa, S; Cellár, R; Vasko, G

2010-08-01

Acute injuries of the lateral ankle ligaments are one of the most common form of injury involving the musculoskeletal apparatus. Treatment usually range from cast immobilisation or acute surgical repair to functional rehabilitation. The aim of our study was to evaluate the incidence of different grades of acute injuries of lateral ligaments of the ankle joint in our patients group and to compare the results of non surgical versus surgical treatment of third grade injuries. 3148 patients were treated for acute lateral ankle sprain in a period of 5 years at our department. Each patient had stress X-ray of the ankle for evaluation of instability at the first visit. From the 234 patients with third grade injury, 39 were enrolled in our study with non surgical treatment and 18 with surgical treatment. Each group was divided regarding to the age in two subgroups. Functional outcome was evaluated 12 and 24 months after injury with AOFAS clinical rating scale and Sports Ankle Rating System--Single Assessment Numeric Evaluation. Statistical analysis was done with Pearson's Chi quadrate test with P < 0.05. First grade injury was present in 62%, second grade in 31% and only 7% of the patients had third grade injury of the lateral ankle ligaments. Further only third grade injuries were studied. Statistically significant better results were seen in patients under the age of 25, in the patient group with surgical treatment compared to patients over 25 years of age. Also statistically significant better results were seen in patient with surgical treatment to non surgical treatment in each age group. No significant difference was observed in the non surgical treatment group regarding to age. Although the injuries of the ankle ligaments belong to the most common injuries of the musculoskeletal system, there is no consensus in the treatment of such disorders. Our experiences and the results of our study show, that surgical treatment in indicated cases provides better results in

Drosophila Neuronal Injury Follows a Temporal Sequence of Cellular Events Leading to Degeneration at the Neuromuscular Junction

PubMed Central

Lincoln, Barron L.; Alabsi, Sahar H.; Frendo, Nicholas; Freund, Robert; Keller, Lani C.

2015-01-01

Neurodegenerative diseases affect millions of people worldwide, and as the global population ages, there is a critical need to improve our understanding of the molecular and cellular mechanisms that drive neurodegeneration. At the molecular level, neurodegeneration involves the activation of complex signaling pathways that drive the active destruction of neurons and their intracellular components. Here, we use an in vivo motor neuron injury assay to acutely induce neurodegeneration in order to follow the temporal order of events that occur following injury in Drosophila melanogaster. We find that sites of injury can be rapidly identified based on structural defects to the neuronal cytoskeleton that result in disrupted axonal transport. Additionally, the neuromuscular junction accumulates ubiquitinated proteins prior to the neurodegenerative events, occurring at 24 hours post injury. Our data provide insights into the early molecular events that occur during axonal and neuromuscular degeneration in a genetically tractable model organism. Importantly, the mechanisms that mediate neurodegeneration in flies are conserved in humans. Thus, these studies have implications for our understanding of the cellular and molecular events that occur in humans and will facilitate the identification of biomedically relevant targets for future treatments. PMID:26512206

Reciprocal Risk of Acute Kidney Injury and Acute Respiratory Distress Syndrome in Critically Ill Burn Patients.

PubMed

Clemens, Michael S; Stewart, Ian J; Sosnov, Jonathan A; Howard, Jeffrey T; Belenkiy, Slava M; Sine, Christy R; Henderson, Jonathan L; Buel, Allison R; Batchinsky, Andriy I; Cancio, Leopoldo C; Chung, Kevin K

2016-10-01

To evaluate the association between acute respiratory distress syndrome and acute kidney injury with respect to their contributions to mortality in critically ill patients. Retrospective analysis of consecutive adult burn patients requiring mechanical ventilation. A 16-bed burn ICU at tertiary military teaching hospital. Adult patients more than 18 years old requiring mechanical ventilation during their initial admission to our burn ICU from January 1, 2003, to December 31, 2011. None. A total 830 patients were included, of whom 48.2% had acute kidney injury (n = 400). These patients had a 73% increased risk of developing acute respiratory distress syndrome after controlling for age, gender, total body surface area burned, and inhalation injury (hazard ratio, 1.73; 95% CI, 1.18-2.54; p = 0.005). In a reciprocal multivariate analysis, acute respiratory distress syndrome (n = 299; 36%) demonstrated a strong trend toward developing acute kidney injury (hazard ratio, 1.39; 95% CI, 0.99-1.95; p = 0.05). There was a 24% overall in-hospital mortality (n = 198). After adjusting for the aforementioned confounders, both acute kidney injury (hazard ratio, 3.73; 95% CI, 2.39-5.82; p < 0.001) and acute respiratory distress syndrome (hazard ratio, 2.16; 95% CI, 1.58-2.94; p < 0.001) significantly contributed to mortality. Age, total body surface area burned, and inhalation injury were also significantly associated with increased mortality. Acute kidney injury increases the risk of acute respiratory distress syndrome in mechanically ventilated burn patients, whereas acute respiratory distress syndrome similarly demonstrates a strong trend toward the development of acute kidney injury. Acute kidney injury and acute respiratory distress syndrome are both independent risks for subsequent death. Future research should look at this interplay for possible early interventions.

Alveolar Edema Fluid Clearance and Acute Lung Injury

PubMed Central

Berthiaume, Yves; Matthay, Michael A.

2009-01-01

Although lung-protective ventilation strategies have substantially reduced mortality of acute lung injury patients there is still a need for new therapies that can further decrease mortality in patients with acute lung injury. Studies of epithelial ion and fluid transport across the distal pulmonary epithelia have provided important new concepts regarding potential new therapies for acute lung injury. Overall, there is convincing evidence that the alveolar epithelium is not only a tight epithelial barrier that resists the movement of edema fluid into the alveoli, but it is also actively involved in the transport of ions and solutes, a process that is essential for edema fluid clearance and the resolution of acute lung injury. The objective of this article is to consider some areas of recent progress in the field of alveolar fluid transport under normal and pathologic conditions. Vectorial ion transport across the alveolar and distal airway epithelia is the primary determinant of alveolar fluid clearance. The general paradigm is that active Na+ and Cl− transport drives net alveolar fluid clearance, as demonstrated in several different species, including the human lung. Although these transport processes can be impaired in severe lung injury, multiple experimental studies suggest that upregulation of Na+ and Cl− transport might be an effective therapy in acute lung injury. We will review mechanisms involved in pharmacological modulation of ion transport in lung injury with a special focus on the use of β-adrenergic agonists which has generated considerable interest and is a promising therapy for clinical acute lung injury. PMID:17604701

[Perioperative acute kidney injury and failure].

PubMed

Chhor, Vibol; Journois, Didier

2014-04-01

Perioperative period is very likely to lead to acute renal failure because of anesthesia (general or perimedullary) and/or surgery which can cause acute kidney injury. Characterization of acute renal failure is based on serum creatinine level which is imprecise during and following surgery. Studies are based on various definitions of acute renal failure with different thresholds which skewed their comparisons. The RIFLE classification (risk, injury, failure, loss, end stage kidney disease) allows clinicians to distinguish in a similar manner between different stages of acute kidney injury rather than using a unique definition of acute renal failure. Acute renal failure during the perioperative period can mainly be explained by iatrogenic, hemodynamic or surgical causes and can result in an increased morbi-mortality. Prevention of this complication requires hemodynamic optimization (venous return, cardiac output, vascular resistance), discontinuation of nephrotoxic drugs but also knowledge of the different steps of the surgery to avoid further degradation of renal perfusion. Diuretics do not prevent acute renal failure and may even push it forward especially during the perioperative period when venous retourn is already reduced. Edema or weight gain following surgery are not correlated with the vascular compartment volume, much less with renal perfusion. Treatment of perioperative acute renal failure is similar to other acute renal failure. Renal replacement therapy must be mastered to prevent any additional risk of hemodynamic instability or hydro-electrolytic imbalance. Copyright © 2014 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Evaluating the Performance of the Pediatric Acute Lung Injury Consensus Conference Definition of Acute Respiratory Distress Syndrome.

PubMed

Parvathaneni, Kaushik; Belani, Sanjay; Leung, Dennis; Newth, Christopher J L; Khemani, Robinder G

2017-01-01

The Pediatric Acute Lung Injury Consensus Conference has developed a pediatric-specific definition of acute respiratory distress syndrome, which is a significant departure from both the Berlin and American European Consensus Conference definitions. We sought to test the external validity and potential impact of the Pediatric Acute Lung Injury Consensus Conference definition by comparing the number of cases of acute respiratory distress syndrome and mortality rates among children admitted to a multidisciplinary PICU when classified by Pediatric Acute Lung Injury Consensus Conference, Berlin, and American European Consensus Conference criteria. Retrospective cohort study. Tertiary care, university-affiliated PICU. All patients admitted between March 2009 and April 2013 who met inclusion criteria for acute respiratory distress syndrome. None. Of 4,764 patients admitted to the ICU, 278 (5.8%) met Pediatric Acute Lung Injury Consensus Conference pediatric acute respiratory distress syndrome criteria with a mortality rate of 22.7%. One hundred forty-three (32.2% mortality) met Berlin criteria, and 134 (30.6% mortality) met American European Consensus Conference criteria. All patients who met American European Consensus Conference criteria and 141 (98.6%) patients who met Berlin criteria also met Pediatric Acute Lung Injury Consensus Conference criteria. The 137 patients who met Pediatric Acute Lung Injury Consensus Conference but not Berlin criteria had an overall mortality rate of 13.1%, but 29 had severe acute respiratory distress syndrome with 31.0% mortality. At acute respiratory distress syndrome onset, there was minimal difference in mortality between mild or moderate acute respiratory distress syndrome by both Berlin (32.4% vs 25.0%, respectively) and Pediatric Acute Lung Injury Consensus Conference (16.7% vs 18.6%, respectively) criteria, but higher mortality for severe acute respiratory distress syndrome (Berlin, 43.6%; Pediatric Acute Lung Injury Consensus

Epidemiology of Overuse and Acute Injuries Among Competitive Collegiate Athletes

PubMed Central

Yang, Jingzhen; Tibbetts, Abigail S.; Covassin, Tracey; Cheng, Gang; Nayar, Saloni; Heiden, Erin

2012-01-01

Context: Although overuse injuries are gaining attention, epidemiologic studies on overuse injuries in male and female collegiate athletes are lacking. (70.7%) acute injuries were reported. The overall injury rate was Objective: To report the epidemiology of overuse injuries sustained by collegiate athletes and to compare the rates of overuse and acute injuries. Design: Descriptive epidemiology study. Setting: A National Collegiate Athletic Association Division I university. Patients or Other Participants: A total of 1317 reported injuries sustained by 573 male and female athletes in 16 collegiate sports teams during the 2005–2008 seasons. Main Outcome Measure(s): The injury and athlete-exposure (AE) data were obtained from the Sports Injury Monitoring System. An injury was coded as either overuse or acute based on the nature of injury. Injury rate was calculated as the total number of overuse (or acute) injuries during the study period divided by the total number of AEs during the same period. Results: A total of 386 (29.3%) overuse injuries and 931 63.1 per 10000 AEs. The rate ratio (RR) of acute versus overuse injuries was 2.34 (95% confidence interval [CI] = 2.05, 2.67). Football had the highest RR (RR = 8.35, 95% CI = 5.38, 12.97), and women's rowing had the lowest (RR = 0.75, 95% CI = 0.51, 1.10). Men had a higher acute injury rate than women (49.8 versus 38.6 per 10000 AEs). Female athletes had a higher rate of overuse injury than male athletes (24.6 versus 13.2 per 10000 AEs). More than half of the overuse injuries (50.8%) resulted in no time loss from sport. Conclusions: Additional studies are needed to examine why female athletes are at greater risk for overuse injuries and identify the best practices for prevention and rehabilitation of overuse injuries. PMID:22488286

Plasma copeptin level predicts acute traumatic coagulopathy and progressive hemorrhagic injury after traumatic brain injury.

PubMed

Yang, Ding-Bo; Yu, Wen-Hua; Dong, Xiao-Qiao; Du, Quan; Shen, Yong-Feng; Zhang, Zu-Yong; Zhu, Qiang; Che, Zhi-Hao; Liu, Qun-Jie; Wang, Hao; Jiang, Li; Du, Yuan-Feng

2014-08-01

Higher plasma copeptin levels correlate with poor clinical outcomes after traumatic brain injury. Nevertheless, their links with acute traumatic coagulopathy and progressive hemorrhagic injury are unknown. Therefore, we aimed to investigate the relationship between plasma copeptin levels, acute traumatic coagulopathy and progressive hemorrhagic injury in patients with severe traumatic brain injury. We prospectively studied 100 consecutive patients presenting within 6h from head trauma. Progressive hemorrhagic injury was present when the follow-up computerized tomography scan reported any increase in size or number of the hemorrhagic lesion, including newly developed ones. Acute traumatic coagulopathy was defined as an activated partial thromboplastic time greater than 40s and/or international normalized ratio greater than 1.2 and/or a platelet count less than 120×10(9)/L. We measured plasma copeptin levels on admission using an enzyme-linked immunosorbent assay in a blinded fashion. In multivariate logistic regression analysis, plasma copeptin level emerged as an independent predictor of progressive hemorrhagic injury and acute traumatic coagulopathy. Using receiver operating characteristic curves, we calculated areas under the curve for progressive hemorrhagic injury and acute traumatic coagulopathy. The predictive performance of copeptin was similar to that of Glasgow Coma Scale score. However, copeptin did not obviously improve the predictive value of Glasgow Coma Scale score. Thus, copeptin may help in the prediction of progressive hemorrhagic injury and acute traumatic coagulopathy after traumatic brain injury. Copyright © 2014 Elsevier Inc. All rights reserved.

Risk factors for acute knee injury in female youth football.

PubMed

Hägglund, Martin; Waldén, Markus

2016-03-01

To prospectively evaluate risk factors for acute time-loss knee injury, in particular ACL injury, in female youth football players. Risk factors were studied in 4556 players aged 12-17 years from a randomised controlled trial during the 2009 season. Covariates were both intrinsic (body mass index, age, relative age effect, onset of menarche, previous acute knee injury or ACL injury, current knee complaints, and familial disposition of ACL injury) and extrinsic (no. of training sessions/week, no. of matches/week, match exposure ratio, match play with other teams, and artificial turf exposure). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated from individual variable and multiple Cox regression analyses. Ninety-six acute knee injuries were recorded, 21 of them ACL injuries. Multiple Cox regression showed a fourfold higher ACL injury rate for players with familial disposition of ACL injury (HR 3.57; 95% CI 1.48-8.62). Significant predictor variables for acute knee injury were age >14 years (HR 1.97; 95% CI 1.30-2.97), knee complaints at the start of the season (HR 1.98; 95% CI 1.30-3.02), and familial disposition of ACL injury (HR 1.96; 95% CI 1.22-3.16). No differences in injury rates were seen when playing on artificial turf compared with natural grass. Female youth football players with a familial disposition of ACL injury had an increased risk of ACL injury and acute knee injury. Older players and those with knee complaints at pre-season were more at risk of acute knee injury. Although the predictive values were low, these factors could be used in athlete screening to target preventive interventions. II.

Acceleration of recovery in acute renal failure: from cellular mechanisms of tubular repair to innovative targeted therapies.

PubMed

Abbate, M; Remuzzi, G

1996-05-01

Kidney repair from injury is a major focus of interest for research, both clinical and basic, in the field of acute renal failure. This is so because very little progress has been made during the past several years to improve mortality in hospitalized patients with acute renal failure despite the unique potential of the kidney for complete structural and functional recovery. Novel therapeutic options have recently emerged from the knowledge of molecular mechanisms of tissue injury after ischemia, including pathways of endothelial-leukocyte interaction and epithelial cell aggregation mediated by integrin molecules. These strategies are promising because they may target early mechanisms of leukocyte infiltration and tubular obstruction. However, it seems clear that additional interventions should address the reparative program that potentially leads to the full restoration of kidney structure and function. Thus, acceleration of repair from acute renal failure is achieved experimentally by growth factors which besides different renal actions seem to have in common the ability to stimulate proliferation of surviving tubular epithelial cells. We direct attention to cellular processes which characterize, and possibly have role in, renal repair from acute tubular injury as potential targets of therapy. In addition to proliferation, they include epithelial differentiation and apoptosis. Further investigation in the biology of repair should set the stage for rational design of targeted therapies which may accelerate the pace of recovery and hopefully decrease mortality in such a dramatic and potentially reversible setting.

Pantoprazole-induced acute kidney injury: A case report.

PubMed

Peng, Tao; Hu, Zhao; Zheng, Hongnan; Zhen, Junhui; Ma, Chengjun; Yang, Xiangdong

2018-06-01

The present study reports a case of pantoprazole-induced acute kidney disease. The patient was diagnosed with acute kidney injury with wide interstitial inflammation and eosinophil infiltration. Following 1 month of glucocorticoid therapy, the patient's serum creatinine and urea nitrogen decreased to within normal ranges. The presentation, clinical course, diagnosis and prognosis of pantoprazole-induced acute kidney injury are discussed herein to highlight the importance of early and correct diagnosis for good prognosis. Disease characteristics include short-term increased serum creatinine levels that respond to glucocorticoid treatment. The patient had no history of chronic kidney disease or proteinuria and presented with increased serum creatinine following treatment with pantoprazole. Following the end of pantoprazole treatment, short-term RRT and long-term prednisolone was administered, then serum creatinine returned to normal. Pantoprazole-induced acute kidney injury is commonly misdiagnosed and late diagnosis results in poor patient prognoses. Misdiagnosis leads to the administration of treatments that may exacerbate the condition, so appropriate diagnosis and treatment for pantoprazole-induced acute kidney injury is necessary.

A phase 2 autologous cellular therapy trial in patients with acute, complete spinal cord injury: pragmatics, recruitment, and demographics.

PubMed

Jones, L A T; Lammertse, D P; Charlifue, S B; Kirshblum, S C; Apple, D F; Ragnarsson, K T; Poonian, D; Betz, R R; Knoller, N; Heary, R F; Choudhri, T F; Jenkins, A L; Falci, S P; Snyder, D A

2010-11-01

Post hoc analysis from a randomized controlled cellular therapy trial in acute, complete spinal cord injury (SCI). Description and quantitative review of study logistics, referral patterns, current practice patterns and subject demographics. Subjects were recruited to one of six international study centers. Data are presented from 1816 patients pre-screened, 75 participants screened and 50 randomized. Of the 1816 patients pre-screened, 53.7% did not meet initial study criteria, primarily due to an injury outside the time window (14 days) or failure to meet neurological criteria (complete SCI between C5 motor/C4 sensory and T11). MRIs were obtained on 339 patients; 51.0% were ineligible based on imaging criteria. Of the 75 participants enrolled, 25 failed screening (SF), leaving 50 randomized. The primary reason for SF was based on the neurological exam (51.9%), followed by failure to meet MRI criteria (22.2%). Of the 50 randomized subjects, there were no significant differences in demographics in the active versus control arms. In those participants for whom data was available, 93.8% (45 of 48) of randomized participants received steroids before study entry, whereas 94.0% (47 of 50) had spine surgery before study enrollment. The 'funnel effect' (large numbers of potentially eligible participants with a small number enrolled) impacts all trials, but was particularly challenging in this trial due to eligibility criteria and logistics. Data collected may provide information on current practice patterns and the issues encountered and addressed may facilitate design of future trials.

Acute and delayed neuroinflammatory response following experimental penetrating ballistic brain injury in the rat

PubMed Central

Williams, Anthony J; Wei, Hans H; Dave, Jitendra R; Tortella, Frank C

2007-01-01

Background Neuroinflammation following acute brain trauma is considered to play a prominent role in both the pathological and reconstructive response of the brain to injury. Here we characterize and contrast both an acute and delayed phase of inflammation following experimental penetrating ballistic brain injury (PBBI) in rats out to 7 days post-injury. Methods Quantitative real time PCR (QRT-PCR) was used to evaluate changes in inflammatory gene expression from the brain tissue of rats exposed to a unilateral frontal PBBI. Brain histopathology was assessed using hematoxylin and eosin (H&E), silver staining, and immunoreactivity for astrocytes (GFAP), microglia (OX-18) and the inflammatory proteins IL-1β and ICAM-1. Results Time course analysis of gene expression levels using QRT-PCR indicated a peak increase during the acute phase of the injury between 3–6 h for the cytokines TNF-α (8–11 fold), IL-1β (11–13 fold), and IL-6 (40–74 fold) as well as the cellular adhesion molecules VCAM (2–3 fold), ICAM-1 (7–15 fold), and E-selectin (11–13 fold). Consistent with the upregulation of pro-inflammatory genes, peripheral blood cell infiltration was a prominent post-injury event with peak levels of infiltrating neutrophils (24 h) and macrophages (72 h) observed throughout the core lesion. In regions of the forebrain immediately surrounding the lesion, strong immunoreactivity for activated astrocytes (GFAP) was observed as early as 6 h post-injury followed by prominent microglial reactivity (OX-18) at 72 h and resolution of both cell types in cortical brain regions by day 7. Delayed thalamic inflammation (remote from the primary lesion) was also observed as indicated by both microglial and astrocyte reactivity (72 h to 7 days) concomitant with the presence of fiber degeneration (silver staining). Conclusion In summary, PBBI induces both an acute and delayed neuroinflammatory response occurring in distinct brain regions, which may provide useful diagnostic

Age and Diet Affect Genetically Separable Secondary Injuries that Cause Acute Mortality Following Traumatic Brain Injury in Drosophila

PubMed Central

Katzenberger, Rebeccah J.; Ganetzky, Barry; Wassarman, David A.

2016-01-01

Outcomes of traumatic brain injury (TBI) vary because of differences in primary and secondary injuries. Primary injuries occur at the time of a traumatic event, whereas secondary injuries occur later as a result of cellular and molecular events activated in the brain and other tissues by primary injuries. We used a Drosophila melanogaster TBI model to investigate secondary injuries that cause acute mortality. By analyzing mortality percentage within 24 hr of primary injuries, we previously found that age at the time of primary injuries and diet afterward affect the severity of secondary injuries. Here, we show that secondary injuries peaked in activity 1–8 hr after primary injuries. Additionally, we demonstrate that age and diet activated distinct secondary injuries in a genotype-specific manner, and that concurrent activation of age- and diet-regulated secondary injuries synergistically increased mortality. To identify genes involved in secondary injuries that cause mortality, we compared genome-wide mRNA expression profiles of uninjured and injured flies under age and diet conditions that had different mortalities. During the peak period of secondary injuries, innate immune response genes were the predominant class of genes that changed expression. Furthermore, age and diet affected the magnitude of the change in expression of some innate immune response genes, suggesting roles for these genes in inhibiting secondary injuries that cause mortality. Our results indicate that the complexity of TBI outcomes is due in part to distinct, genetically controlled, age- and diet-regulated mechanisms that promote secondary injuries and that involve a subset of innate immune response genes. PMID:27754853

Adrenocorticotropic hormone ameliorates acute kidney injury by steroidogenic-dependent and -independent mechanisms

PubMed Central

Si, Jin; Ge, Yan; Zhuang, Shougang; Juan Wang, Li; Chen, Shan; Gong, Rujun

2013-01-01

Adrenocorticotropic hormone (ACTH) has a renoprotective effect in chronic kidney disease; however, its effect on acute kidney injury (AKI) remains unknown. In a rat model of tumor necrosis factor (TNF)–induced AKI, we found that ACTH gel prevented kidney injury, corrected acute renal dysfunction, and improved survival. Morphologically, ACTH gel ameliorated TNF-induced acute tubular necrosis, associated with a reduction in tubular apoptosis. While the steroidogenic response to ACTH gel plateaued, the kidney-protective effect continued to increase at even higher doses, suggesting steroid-independent mechanisms. Of note, ACTH also acts as a key agonist of the melanocortin system, with its cognate melanocortin 1 receptor (MC1R) abundantly expressed in renal tubules. In TNF-injured tubular epithelial cells in vitro, ACTH reinstated cellular viability and eliminated apoptosis. This beneficial effect was blunted in MC1R-silenced cells, suggesting that this receptor mediates the anti-apoptotic signaling of ACTH. Moreover, ACTH gel protected mice against cecal ligation puncture–induced septic AKI better than α-melanocyte-stimulating hormone: a protein equal in biological activity to ACTH except for steroidogenesis. Thus, ACTH has additive renoprotective actions achieved by both steroid-dependent mechanisms and MC1R-directed anti-apoptosis. ACTH may represent a novel therapeutic strategy to prevent or treat AKI. PMID:23325074

Trends in Hospitalizations for Acute Kidney Injury - United States, 2000-2014.

PubMed

Pavkov, Meda E; Harding, Jessica L; Burrows, Nilka R

2018-03-16

Acute kidney injury is a sudden decrease in kidney function with or without kidney damage, occurring over a few hours or days. Diabetes, hypertension, and advanced age are primary risk factors for acute kidney injury. It is increasingly recognized as an in-hospital complication of sepsis, heart conditions, and surgery (1,2). Its most severe stage requires treatment with dialysis. Acute kidney injury is also associated with higher likelihood of long-term care, incidence of chronic kidney disease and hospital mortality, and health care costs (1,2). Although a number of U.S. studies have indicated an increasing incidence of dialysis-treated acute kidney injury since the late 1990s (3), no data are available on national trends in diabetes-related acute kidney injury. To estimate diabetes- and nondiabetes-related acute kidney injury trends, CDC analyzed 2000-2014 data from the National Inpatient Sample (NIS) (4) and the National Health Interview Survey (NHIS) (5). Age-standardized rates of acute kidney injury hospitalizations increased by 139% (from 23.1 to 55.3 per 1,000 persons) among adults with diagnosed diabetes, and by 230% (from 3.5 to 11.7 per 1,000 persons) among those without diabetes. Improving both patient and provider awareness that diabetes, hypertension, and advancing age are frequently associated with acute kidney injury might reduce its occurrence and improve management of the underlying diseases in an aging population.

Postoperative acute kidney injury following intraoperative blood product transfusions during cardiac surgery.

PubMed

Kindzelski, Bogdan A; Corcoran, Philip; Siegenthaler, Michael P; Horvath, Keith A

2018-01-01

This study explored the nature of the association between intraoperative usage of red blood cell, fresh frozen plasma, cryoprecipitate or platelet transfusions and acute kidney injury. A total of 1175 patients who underwent cardiac surgery between 2008 and 2013 were retrospectively analyzed. We assessed the association between: (1) preoperative patient characteristics and acute kidney injury, (2) intraoperative blood product usage and acute kidney injury, (3) acute kidney injury and 30-day mortality or re-hospitalization. In our cohort of 1175 patients, 288 patients (24.5%) developed acute kidney injury. This included 162 (13.8%), 69 (5.9%) and 57 (4.9%) developing stage 1, stage 2 or stage 3 acute kidney injury, respectively. Increased red blood cell, fresh frozen plasma or platelet transfusions increased the odds of developing acute kidney injury. Specifically, every unit of red blood cells, fresh frozen plasma or platelets transfused was associated with an increase in the covariate-adjusted odds ratio of developing ⩾ stage 2 kidney injury of 1.18, 1.19 and 1.04, respectively. Intraoperative blood product transfusions were independently associated with an increased odds of developing acute kidney injury following cardiac surgery. Further randomized studies are needed to better define intraoperative transfusion criteria.

Training loads and injury risk in Australian football—differing acute: chronic workload ratios influence match injury risk

PubMed Central

Carey, David L; Blanch, Peter; Ong, Kok-Leong; Crossley, Kay M; Crow, Justin; Morris, Meg E

2017-01-01

Aims (1) To investigate whether a daily acute:chronic workload ratio informs injury risk in Australian football players; (2) to identify which combination of workload variable, acute and chronic time window best explains injury likelihood. Methods Workload and injury data were collected from 53 athletes over 2 seasons in a professional Australian football club. Acute:chronic workload ratios were calculated daily for each athlete, and modelled against non-contact injury likelihood using a quadratic relationship. 6 workload variables, 8 acute time windows (2–9 days) and 7 chronic time windows (14–35 days) were considered (336 combinations). Each parameter combination was compared for injury likelihood fit (using R2). Results The ratio of moderate speed running workload (18–24 km/h) in the previous 3 days (acute time window) compared with the previous 21 days (chronic time window) best explained the injury likelihood in matches (R2=0.79) and in the immediate 2 or 5 days following matches (R2=0.76–0.82). The 3:21 acute:chronic workload ratio discriminated between high-risk and low-risk athletes (relative risk=1.98–2.43). Using the previous 6 days to calculate the acute workload time window yielded similar results. The choice of acute time window significantly influenced model performance and appeared to reflect the competition and training schedule. Conclusions Daily workload ratios can inform injury risk in Australian football. Clinicians and conditioning coaches should consider the sport-specific schedule of competition and training when choosing acute and chronic time windows. For Australian football, the ratio of moderate speed running in a 3-day or 6-day acute time window and a 21-day chronic time window best explained injury risk. PMID:27789430

Acute liver injury induced by weight-loss herbal supplements.

PubMed

Chen, Gary C; Ramanathan, Vivek S; Law, David; Funchain, Pauline; Chen, George C; French, Samuel; Shlopov, Boris; Eysselein, Viktor; Chung, David; Reicher, Sonya; Pham, Binh V

2010-11-27

We report three cases of patients with acute liver injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients demonstrated findings consistent with drug-induced acute liver injury. To our knowledge, we are the first institute to report acute liver injury from both of these two types of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a cautious approach when consuming herbal supplements for the purpose of weight loss.

Acute liver injury induced by weight-loss herbal supplements

PubMed Central

Chen, Gary C; Ramanathan, Vivek S; Law, David; Funchain, Pauline; Chen, George C; French, Samuel; Shlopov, Boris; Eysselein, Viktor; Chung, David; Reicher, Sonya; Pham, Binh V

2010-01-01

We report three cases of patients with acute liver injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients demonstrated findings consistent with drug-induced acute liver injury. To our knowledge, we are the first institute to report acute liver injury from both of these two types of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a cautious approach when consuming herbal supplements for the purpose of weight loss. PMID:21173910

Current approaches to prevention of contrast induced acute kidney injury.

PubMed

Blandon, Jimena; Mukherjee, Debabrata

2011-10-01

Contrast-induced acute kidney injury is one of the leading causes of hospital-acquired acute kidney injury. Thus far, no strategies have been clearly shown to be effective in preventing contrast-induced acute kidney injury beyond thorough patient selection, meticulous hydration of the patient, and minimizing the amount of contrast used. Additional studies are needed to define the optimal means of hydration, role of commonly advocated prophylaxis strategies such as N-acetylcysteine and develop newer more novel effective therapies to prevent or minimize the risk of kidney injury.

Changing interdigestive migrating motor complex in rats under acute liver injury.

PubMed

Liu, Mei; Zheng, Su-Jun; Xu, Weihong; Zhang, Jianying; Chen, Yu; Duan, Zhongping

2014-01-01

Gastrointestinal motility disorder is a major clinical manifestation of acute liver injury, and interdigestive migrating motor complex (MMC) is an important indicator. We investigated the changes and characteristics of MMC in rats with acute liver injury. Acute liver injury was created by d-galactosamine, and we recorded the interdigestive MMC using a multichannel physiological recorder and compared the indexes of interdigestive MMC. Compared with normal controls, antral MMC Phase I duration was significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury. The duodenal MMC cycle and MMC Phases I and IV duration were significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury. The jejunal MMC cycle and MMC Phases I and IV duration were significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury compared with normal controls. Compared with the normal controls, rats with acute liver injury had a significantly prolonged interdigestive MMC cycle, related mainly to longer MMC Phases I and IV, shortened MMC Phase III, and MMC Phase II characterized by increased migrating clustered contractions, which were probably major contributors to the gastrointestinal motility disorders.

Precision Medicine for Acute Kidney Injury (AKI): Redefining AKI by Agnostic Kidney Tissue Interrogation and Genetics.

PubMed

Kiryluk, Krzysztof; Bomback, Andrew S; Cheng, Yim-Ling; Xu, Katherine; Camara, Pablo G; Rabadan, Raul; Sims, Peter A; Barasch, Jonathan

2018-01-01

Acute kidney injury (AKI) currently is diagnosed by a temporal trend of a single blood analyte: serum creatinine. This measurement is neither sensitive nor specific to kidney injury or its protean forms. Newer biomarkers, neutrophil gelatinase-associated lipocalin (NGAL, Lipocalin 2, Siderocalin), or kidney injury molecule-1 (KIM-1, Hepatitis A Virus Cellular Receptor 1), accelerate the diagnosis of AKI as well as prospectively distinguish rapidly reversible from prolonged causes of serum creatinine increase. Nonetheless, these biomarkers lack the capacity to subfractionate AKI further (eg, sepsis versus ischemia versus nephrotoxicity from medications, enzymes, or metals) or inform us about the primary and secondary sites of injury. It also is unknown whether all nephrons are injured in AKI, whether all cells in a nephron are affected, and whether injury responses can be stimulus-specific or cell type-specific or both. In this review, we summarize fully agnostic tissue interrogation approaches that may help to redefine AKI in cellular and molecular terms, including single-cell and single-nuclei RNA sequencing technology. These approaches will empower a shift in the current paradigm of AKI diagnosis, classification, and staging, and provide the renal community with a significant advance toward precision medicine in the analysis AKI. Copyright © 2017 Elsevier Inc. All rights reserved.

Trauma-associated lung injury differs clinically and biologically from acute lung injury due to other clinical disorders*

PubMed Central

Calfee, Carolyn S.; Eisner, Mark D.; Ware, Lorraine B.; Thompson, B. Taylor; Parsons, Polly E.; Wheeler, Arthur P.; Korpak, Anna; Matthay, Michael A.

2009-01-01

Objective Patients with trauma-associated acute lung injury have better outcomes than patients with other clinical risks for lung injury, but the mechanisms behind these improved outcomes are unclear. We sought to compare the clinical and biological features of patients with trauma-associated lung injury with those of patients with other risks for lung injury and to determine whether the improved outcomes of trauma patients reflect their baseline health status or less severe lung injury, or both. Design, Setting, and Patients Analysis of clinical and biological data from 1,451 patients enrolled in two large randomized, controlled trials of ventilator management in acute lung injury. Measurements and Main Results Compared with patients with other clinical risks for lung injury, trauma patients were younger and generally less acutely and chronically ill. Even after adjusting for these baseline differences, trauma patients had significantly lower plasma levels of intercellular adhesion molecule-1, von Willebrand factor antigen, surfactant protein-D, and soluble tumor necrosis factor receptor-1, which are biomarkers of lung epithelial and endothelial injury previously found to be prognostic in acute lung injury. In contrast, markers of acute inflammation, except for interleukin-6, and disordered coagulation were similar in trauma and nontrauma patients. Trauma-associated lung injury patients had a significantly lower odds of death at 90 days, even after adjusting for baseline clinical factors including age, gender, ethnicity, comorbidities, and severity of illness (odds ratio, 0.44; 95% confidence interval, 0.24 – 0.82; p = .01). Conclusions Patients with trauma-associated lung injury are less acutely and chronically ill than other lung injury patients; however, these baseline clinical differences do not adequately explain their improved outcomes. Instead, the better outcomes of the trauma population may be explained, in part, by less severe lung epithelial and

[What is the potential for acute laparoscopy in penetrating abdominal injuries?].

PubMed

Petrás, D; Javora, J

2004-03-01

The aim of this work was to show current opinions on performing acute laparoscopic exploration in penetrating injuries of the abdomen and to assess the authors' own experience in performing the above operation in conditions of the regional hospital. The authors present 17 patients treated between the years 1997-2002 for penetrating injuries of the abdomen or suspected for a penetrating injury. Acute laparotomy was performed in 11 cases, acute laparoscopy in 6 patients. The authors specify certain indications which lead to the acute laparoscopy, the method performed and its diagnostic value. In the group observed, an intraabdominal injury was diagnosed in 41% of the patients, in 59% of cases findings were negative. When the intraabdominal injuries were assessed, the group of the acute laparotomies had 54% of negative findings, the group of the acute laparoscopies had 66.6% of negative findings. Laparoscopy decreased the total number of all negative laparotomies from 59% down to 35%. Diagnostic laparotomy fits to complement a spectrum of examination methods. Especially in equivocal cases, when a penetrating injury is suspected, it decreases the number of so called "necessary" non-therapeutic laparotomies to a minimum. It is most efficient, compared to other diagnostic methods, in verifying injuries of the peritoneum and diaphragm. However, acute laparoscopy should be always performed by an experienced surgeon. A therapeutic potential of the acute laparoscopy depend on proficiency of the operating surgeon and on the technical potential of each hospital. However, they, mostly, still remain restricted to caring for minor, isolated intraabdominal injuries.

Hepatoprotectant Ursodeoxycholyl Lysophosphatidylethanolamide Increasing Phosphatidylcholine Levels as a Potential Therapy of Acute Liver Injury

PubMed Central

Chamulitrat, Walee; Zhang, Wujuan; Xu, Weihong; Pathil, Anita; Setchell, Kenneth; Stremmel, Wolfgang

2012-01-01

It has been long known that hepatic synthesis of phosphatidylcholine (PC) is depressed during acute such as carbon tetrachloride-induced liver injury. Anti-hepatotoxic properties of PC as liposomes have been recognized for treatment of acute liver damage. Ursodeoxycholate (UDCA) is a known hepatoprotectant in stabilizing cellular membrane. For therapeutic management of liver injury, we coupled UDCA with a phospholipid known as ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE). UDCA-LPE has been shown to first-in-class hepatoprotectant being superior to UDCA or PC. It inhibits mitochondrial damage and apoptosis, elicits survival signaling pathway, and promotes regeneration of hepatocytes. We herein report that a unique contribution of UDCA-LPE in increasing concentrations of PC in vitro and in vivo. UDCA-LPE-treated hepatocytes contained significantly increased PC levels. UDCA-LPE underwent the hydrolysis to LPE which was not the precursor of the increased PC. The levels of PC in the liver and blood were increased rapidly after intraperitoneally administration UDCA-LPE, and were found to be sustained even after 24 h. Among PC synthesis genes tested, UDCA-LPE treatment of mouse hepatocytes increased transcription of CDP-diacylglycerol synthase 1 which is an enzyme catalyzing phosphatidic acid to generate intermediates for PC synthesis. Thus, UDCA-LPE as a hepatoprotectant was able to induce synthesis of protective PC which would supplement for the loss of PC occurring during acute liver injury. This property has placed UDCA-LPE as a candidate agent for therapy of acute hepatotoxicity such as acetaminophen poisoning. PMID:22363296

Endoplasmic Reticulum Stress in Ischemic and Nephrotoxic Acute Kidney Injury.

PubMed

Yan, Mingjuan; Shu, Shaoqun; Guo, Chunyuan; Tang, Chengyuan; Dong, Zheng

2018-06-12

Acute kidney injury is a medical condition characterized by kidney damage with a rapid decline of renal function, which is associated with high mortality and morbidity. Recent research has further established an intimate relationship between acute kidney injury and chronic kidney disease. Perturbations of kidney cells in acute kidney injury result in the accumulation of unfolded and misfolded proteins in the endoplasmic reticulum, leading to unfolded protein response or endoplasmic reticulum stress. In this review, we analyze the role and regulation of endoplasmic reticulum stress in acute kidney injury triggered by renal ischemia-reperfusion and cisplatin nephrotoxicity. The balance between the two major components of unfolded protein response, the adaptive pathway and the apoptotic pathway, plays a critical role in determining the cell fate in endoplasmic reticulum stress. The adaptive pathway is evoked to attenuate translation, induce chaperones, maintain protein homeostasis, and promote cell survival. Prolonged endoplasmic reticulum stress activates the apoptotic pathway, resulting in the elimination of dysfunctional cells. Therefore, regulating ER stress in kidney cells may provide a therapeutic target in acute kidney injury.

Functional genomics of chlorine-induced acute lung injury in mice.

PubMed

Leikauf, George D; Pope-Varsalona, Hannah; Concel, Vincent J; Liu, Pengyuan; Bein, Kiflai; Brant, Kelly A; Dopico, Richard A; Di, Y Peter; Jang, An-Soo; Dietsch, Maggie; Medvedovic, Mario; Li, Qian; Vuga, Louis J; Kaminski, Naftali; You, Ming; Prows, Daniel R

2010-07-01

Acute lung injury can be induced indirectly (e.g., sepsis) or directly (e.g., chlorine inhalation). Because treatment is still limited to supportive measures, mortality remains high ( approximately 74,500 deaths/yr). In the past, accidental (railroad derailments) and intentional (Iraq terrorism) chlorine exposures have led to deaths and hospitalizations from acute lung injury. To better understand the molecular events controlling chlorine-induced acute lung injury, we have developed a functional genomics approach using inbred mice strains. Various mouse strains were exposed to chlorine (45 ppm x 24 h) and survival was monitored. The most divergent strains varied by more than threefold in mean survival time, supporting the likelihood of an underlying genetic basis of susceptibility. These divergent strains are excellent models for additional genetic analysis to identify critical candidate genes controlling chlorine-induced acute lung injury. Gene-targeted mice then could be used to test the functional significance of susceptibility candidate genes, which could be valuable in revealing novel insights into the biology of acute lung injury.

Acute Inhalation Injury

PubMed Central

Gorguner, Metin; Akgun, Metin

2010-01-01

Inhaled substances may cause injury in pulmonary epithelium at various levels of respiratory tract, leading from simple symptoms to severe disease. Acute inhalation injury (AII) is not uncommon condition. There are certain high risk groups but AII may occur at various places including home or workplace. Environmental exposure is also possible. In addition to individual susceptibility, the characteristics of inhaled substances such as water solubility, size of substances and chemical properties may affect disease severity as well as its location. Although AII cases may recover in a few days but AII may cause long-term complications, even death. We aimed to discuss the effects of short-term exposures (minutes to hours) to toxic substances on the lungs. PMID:25610115

Training loads and injury risk in Australian football-differing acute: chronic workload ratios influence match injury risk.

PubMed

Carey, David L; Blanch, Peter; Ong, Kok-Leong; Crossley, Kay M; Crow, Justin; Morris, Meg E

2017-08-01

(1) To investigate whether a daily acute:chronic workload ratio informs injury risk in Australian football players; (2) to identify which combination of workload variable, acute and chronic time window best explains injury likelihood. Workload and injury data were collected from 53 athletes over 2 seasons in a professional Australian football club. Acute:chronic workload ratios were calculated daily for each athlete, and modelled against non-contact injury likelihood using a quadratic relationship. 6 workload variables, 8 acute time windows (2-9 days) and 7 chronic time windows (14-35 days) were considered (336 combinations). Each parameter combination was compared for injury likelihood fit (using R 2 ). The ratio of moderate speed running workload (18-24 km/h) in the previous 3 days (acute time window) compared with the previous 21 days (chronic time window) best explained the injury likelihood in matches (R 2 =0.79) and in the immediate 2 or 5 days following matches (R 2 =0.76-0.82). The 3:21 acute:chronic workload ratio discriminated between high-risk and low-risk athletes (relative risk=1.98-2.43). Using the previous 6 days to calculate the acute workload time window yielded similar results. The choice of acute time window significantly influenced model performance and appeared to reflect the competition and training schedule. Daily workload ratios can inform injury risk in Australian football. Clinicians and conditioning coaches should consider the sport-specific schedule of competition and training when choosing acute and chronic time windows. For Australian football, the ratio of moderate speed running in a 3-day or 6-day acute time window and a 21-day chronic time window best explained injury risk. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Melatonin prevents acute kidney injury in severely burned rats via the activation of SIRT1

PubMed Central

Bai, Xiao-Zhi; He, Ting; Gao, Jian-Xin; Liu, Yang; Liu, Jia-Qi; Han, Shi-Chao; Li, Yan; Shi, Ji-Hong; Han, Jun-Tao; Tao, Ke; Xie, Song-Tao; Wang, Hong-Tao; Hu, Da-Hai

2016-01-01

Acute kidney injury (AKI) is a common complication after severe burns. Melatonin has been reported to protect against multiple organ injuries by increasing the expression of SIRT1, a silent information regulator that regulates stress responses, inflammation, cellular senescence and apoptosis. This study aimed to investigate the protective effects of melatonin on renal tissues of burned rats and the role of SIRT1 involving the effects. Rat severely burned model was established, with or without the administration of melatonin and SIRT1 inhibitor. The renal function and histological manifestations were determined to evaluate the severity of kidney injury. The levels of acetylated-p53 (Ac-p53), acetylated-p65 (Ac-p65), NF-κB, acetylated-forkhead box O1 (Ac-FoxO1), Bcl-2 and Bax were analyzed to study the underlying mechanisms. Our results suggested that severe burns could induce acute kidney injury, which could be partially reversed by melatonin. Melatonin attenuated oxidative stress, inflammation and apoptosis accompanied by the increased expression of SIRT1. The protective effects of melatonin were abrogated by the inhibition of SIRT1. In conclusion, we demonstrate that melatonin improves severe burn-induced AKI via the activation of SIRT1 signaling. PMID:27599451

Melatonin prevents acute kidney injury in severely burned rats via the activation of SIRT1.

PubMed

Bai, Xiao-Zhi; He, Ting; Gao, Jian-Xin; Liu, Yang; Liu, Jia-Qi; Han, Shi-Chao; Li, Yan; Shi, Ji-Hong; Han, Jun-Tao; Tao, Ke; Xie, Song-Tao; Wang, Hong-Tao; Hu, Da-Hai

2016-09-07

Acute kidney injury (AKI) is a common complication after severe burns. Melatonin has been reported to protect against multiple organ injuries by increasing the expression of SIRT1, a silent information regulator that regulates stress responses, inflammation, cellular senescence and apoptosis. This study aimed to investigate the protective effects of melatonin on renal tissues of burned rats and the role of SIRT1 involving the effects. Rat severely burned model was established, with or without the administration of melatonin and SIRT1 inhibitor. The renal function and histological manifestations were determined to evaluate the severity of kidney injury. The levels of acetylated-p53 (Ac-p53), acetylated-p65 (Ac-p65), NF-κB, acetylated-forkhead box O1 (Ac-FoxO1), Bcl-2 and Bax were analyzed to study the underlying mechanisms. Our results suggested that severe burns could induce acute kidney injury, which could be partially reversed by melatonin. Melatonin attenuated oxidative stress, inflammation and apoptosis accompanied by the increased expression of SIRT1. The protective effects of melatonin were abrogated by the inhibition of SIRT1. In conclusion, we demonstrate that melatonin improves severe burn-induced AKI via the activation of SIRT1 signaling.

Molecular and cellular profiling of acute responses to total body radiation exposure in ovariectomized female cynomolgus macaques.

PubMed

DeBo, Ryne J; Register, Thomas C; Caudell, David L; Sempowski, Gregory D; Dugan, Gregory; Gray, Shauna; Owzar, Kouros; Jiang, Chen; Bourland, J Daniel; Chao, Nelson J; Cline, J Mark

2015-06-01

The threat of radiation exposure requires a mechanistic understanding of radiation-induced immune injury and recovery. The study objective was to evaluate responses to ionizing radiation in ovariectomized (surgically post-menopausal) female cynomolgus macaques. Animals received a single total-body irradiation (TBI) exposure at doses of 0, 2 or 5 Gy with scheduled necropsies at 5 days, 8 weeks and 24 weeks post-exposure. Blood and lymphoid tissues were evaluated for morphologic, cellular, and molecular responses. Irradiated animals developed symptoms of acute hematopoietic syndrome, and reductions in thymus weight, thymopoiesis, and bone marrow cellularity. Acute, transient increases in plasma monocyte chemoattractant protein 1 (MCP-1) were observed in 5 Gy animals along with dose-dependent alterations in messenger ribonucleic acid (mRNA) signatures in thymus, spleen, and lymph node. Expression of T cell markers was lower in thymus and spleen, while expression of macrophage marker CD68 (cluster of differentiation 68) was relatively elevated in lymphoid tissues from irradiated animals. Ovariectomized female macaques exposed to moderate doses of radiation experienced increased morbidity, including acute, dose-dependent alterations in systemic and tissue-specific biomarkers, and increased macrophage/T cell ratios. The effects on mortality exceeded expectations based on previous studies in males, warranting further investigation.

Sex differences in acute kidney injury requiring dialysis.

PubMed

Neugarten, Joel; Golestaneh, Ladan; Kolhe, Nitin V

2018-06-08

Female sex has been included as a risk factor in models developed to predict the risk of acute kidney injury (AKI) associated with cardiac surgery, aminoglycoside nephrotoxicity and contrast-induced nephropathy. The commentary acompanying the Kidney Disease Improving Global Outcomes Clinical Practice Guideline for Acute Kidney Injury concludes that female sex is a shared susceptibility factor for acute kidney injury based on observations that female sex is associated with the development of hospital-acquired acute kidney injury. In contrast, female sex is reno-protective in animal models. In this context, we sought to examine the role of sex in hospital-associated acute kidney injury in greater detail. We utilized the Hospital Episode Statistics database to calculate the sex-stratified incidence of AKI requiring renal replacement therapy (AKI-D) among 194,157,726 hospital discharges reported for the years 1998-2013. In addition, we conducted a systematic review of the English literature to evaluate dialysis practices among men versus women with AKI. Hospitalized men were more likely to develop AKI-D than hospitalized women (OR 2.19 (2.15, 2.22) p < 0.0001). We found no evidence in the published literature that dialysis practices differ between men and women with AKI. Based on a population of hospitalized patients which is more than 3 times larger than all previously published cohorts reporting sex-stratified AKI data combined, we conclude that male sex is associated with an increased incidence of hospital-associated AKI-D. Our study is among the first reports to highlight the protective role of female gender in AKI.

Fluid composition and acute kidney injury.

PubMed

Zampieri, Fernando G; Libório, Alexandre B; Cavalcanti, Alexandre B

2016-12-01

To describe recent advances in the understanding of the role of fluid composition in renal outcomes in critically ill patients. The debate on fluid composition is now focused in a pragmatic discussion on fluid electrolyte composition. The resurgence of this debate was propelled by several observational studies that suggested that balanced (i.e., low chloride) solutions were associated with less acute kidney injury in critically ill patients. Nevertheless, a cluster randomized trial failed to show any benefit of balanced solutions. This trial, however, may have failed to detect an effect because of low global illness severity and little fluid infused. If balanced solutions are to be associated with less acute kidney injury, it will probably be in high risk, aggressively resuscitated patients. Additionally, the causal loop involving unbalanced solution infusion, induction of hyperchloremia and acute kidney injury is yet to be closed. Other factors, such as buffer type, speed of infusion and temperature, among others, may also be important. Recent evidence suggests that crystalloid fluid composition matters and can influence renal outcomes in critically ill patients. Further studies should assess the impact and cost-efficiency of balanced solutions in the context of high-risk scenarios.

Tolvaptan rescue contrast-induced acute kidney injury: A case report.

PubMed

Lee, Wei-Chieh; Fang, Hsiu-Yu; Fang, Chih-Yuan

2018-04-01

Contrast-induced acute kidney injury is one of the most serious adverse effects of contrast media and is related to three distinct but interacting mechanisms: medullary ischemia, formation of reactive oxygen species and direct tubular cell toxicity, especially in the patients with chronic kidney disease. The strategies of treatment, including stabilization of hemodynamic parameters and maintenance of normal fluid and electrolyte balance, were similar to the management of other types of acute kidney injury. A 58-year-old woman experienced acute oligouria after complex percutaneous coronary intervention for multiple vessel coronary artery disease. Chest radiography showed pulmonary congestion and hyponatremia was noted after fluid hydration for suspicious contrast-induced nephropathy. Oral tolvaptan, at 15mg per day, was used for three days. Urine output increased gradually and symptoms relieved one day later after using tolvaptan. Serum creatinine also improved to baseline level one week later after this event. Here, we reported an interesting case about contrast-induced acute kidney injury and hypervolemic hyponatremia, where tolvaptan was used to rescue the oliguric phase. Tolvaptan could be considered to use for contrast-induced acute kidney injury and had possibility of prevention from hemodialysis. Larger studies are still needed to investigate the role of tolvaptan in rescuing the oliguric phase in contrast-induced acute kidney injury.

Acute injury and chronic disability resulting from surfboard riding.

PubMed

Taylor, D McD; Bennett, D; Carter, M; Garewal, D; Finch, C F

2004-12-01

We undertook a cross-sectional survey of surfers at eight Victorian beaches between February and May 2003 and analysed acute injury and chronic disability sustained while surfing during the preceding 12 months. Significant injuries were defined as requiring medical attention or time off surfing/work. 646 surfers were enrolled (90.2% male, median age 27 years, median years of surfing 10). 145 surfers sustained 168 significant acute injuries in the preceding 12 months (0.26 injuries/surfer/year, 95% CI 0.22-0.30). Most were caused by striking a surfboard or another surfer (45.2%, 95% CI 37.6-53.1), "wiping out" (36.3%, 95% CI 29.1-44.1) or striking the seabed (17.9%, 95% CI 12.6-24.7). Injuries included lacerations (46.4%, 95% CI 38.8-54.3), sprains (28.6%, 95% CI 22.0-36.1), dislocations (10.7%, 95% CI 6.7-16.6) and fractures (8.9%, 95% CI 5.3-14.6). Body parts most frequently injured were the lower limb (45.8%, 95% CI 38.2-53.7) and the head/face (26.2%, 95% CI 19.9-33.6). Surfing injuries that were treated in Victorian emergency departments over a six year period revealed a similar pattern, although there was a greater proportion of head/face injuries (42.0%, 95% CI 36.0-48.1, p = 0.001). 20 surfers reported long-term effects from acute injuries, mainly unstable/stiff/painful joints. 136 surfers reported chronic health problems not related to acute injury including chronic/recurrent otitis externa and exostoses, muscle and joint pain/stiffness and pterygium. Significant injury while surfing is not uncommon. Although head injury accounts for a considerable proportion, very few surfers wear protective headgear. Greater use of protective headgear should be considered.

Induced hypernatraemia is protective in acute lung injury.

PubMed

Bihari, Shailesh; Dixon, Dani-Louise; Lawrence, Mark D; Bersten, Andrew D

2016-06-15

Sucrose induced hyperosmolarity is lung protective but the safety of administering hyperosmolar sucrose in patients is unknown. Hypertonic saline is commonly used to produce hyperosmolarity aimed at reducing intra cranial pressure in patients with intracranial pathology. Therefore we studied the protective effects of 20% saline in a lipopolysaccharide lung injury rat model. 20% saline was also compared with other commonly used fluids. Following lipopolysaccharide-induced acute lung injury, male Sprague Dawley rats received either 20% hypertonic saline, 0.9% saline, 4% albumin, 20% albumin, 5% glucose or 20% albumin with 5% glucose, i.v. During 2h of non-injurious mechanical ventilation parameters of acute lung injury were assessed. Hypertonic saline resulted in hypernatraemia (160 (1) mmol/l, mean (SD)) maintained through 2h of ventilation, and in amelioration of lung oedema, myeloperoxidase, bronchoalveolar cell infiltrate, total soluble protein and inflammatory cytokines, and lung histological injury score, compared with positive control and all other fluids (p ≤ 0.001). Lung physiology was maintained (conserved PaO2, elastance), associated with preservation of alveolar surfactant (p ≤ 0.0001). Independent of fluid or sodium load, induced hypernatraemia is lung protective in lipopolysaccharide-induced acute lung injury. Copyright © 2016 Elsevier B.V. All rights reserved.

Acute spinal injury after centrifuge training in asymptomatic fighter pilots.

PubMed

Kang, Kyung-Wook; Shin, Young Ho; Kang, Seungcheol

2015-04-01

Many countries have hypergravity training centers using centrifuges for pilots to cope with a high gravity (G) environment. The high G training carries potential risk for the development of spinal injury. However, no studies evaluated the influence of centrifuge training on the spines of asymptomatic fighter pilots on a large scale. Study subjects were 991 male fighter pilots with high G training at one institution. Subject variables included information about physical characteristics, flight hours of pilots prior to the training, and G force exposure related factors during training. The two dependent variables were whether the pilots developed acute spinal injury after training and the severity of the injury (major/minor). The incidence of acute spinal injury after high G training was 2.3% (23 of 991 subjects). There were 19 subjects who developed minor injury and 4 subjects who developed a herniated intervertebral disc, which is considered a major injury. In multivariate analysis, only the magnitude of G force during training was significantly related to the development of acute spinal injury. However, there was no significant factor related to the severity of the injury. These results suggest that high G training could cause negative effects on fighter pilots' spines. The magnitude of G force during training seemed to be the most significant factor affecting the occurrence of acute spinal injury.

Role of renal biomarkers as predictors of acute kidney injury in cardiac surgery.

PubMed

Ghatanatti, Ravi; Teli, Anita; Tirkey, Sundeep Sanjivan; Bhattacharya, Subhankar; Sengupta, Gautam; Mondal, Ansuman

2014-02-01

Cardiac surgery is unique in using cardiopulmonary bypass in various clinical scenarios. Injury of vital organs is unavoidable in the perioperative period. Acute kidney injury is a consequence of the systemic inflammatory response after bypass, emboli, ischemia, and low cardiac output states, reportedly occurring in 30%-40% of open heart surgeries. Acute kidney injury is associated with increased morbidity, mortality, and cost. Many preventive measures (off-pump procedures, decreased crossclamp time, pulsatile flow, adequate hydration) are taken in the perioperative period to avoid organ injury, but in vain. Traditionally, blood urea, serum creatinine, and creatinine clearance rate were applied for prediction of acute kidney injury. The recent emergence of biomarkers such as neutrophil gelatinase-associated lipocalin, cystatin C, liver-type fatty acid binding protein, interleukin-18, kidney injury molecule-1, and tetrahydrobiopterin have helped in detecting acute kidney injury long before the rise of serum creatinine. These biomarkers can also be used as tools for predicting therapeutic effects in acute kidney injury and for monitoring drug toxicity. This review consolidates the knowledge of biomarkers and their application in acute kidney injury management.

Spontaneously regulated vs. controlled ventilation of acute lung injury/acute respiratory distress syndrome.

PubMed

Marini, John J

2011-02-01

To present an updated discussion of those aspects of controlled positive pressure breathing and retained spontaneous regulation of breathing that impact the management of patients whose tissue oxygenation is compromised by acute lung injury. The recent introduction of ventilation techniques geared toward integrating natural breathing rhythms into even the earliest phase of acute respiratory distress syndrome support (e.g., airway pressure release, proportional assist ventilation, and neurally adjusted ventilatory assist), has stimulated a burst of new investigations. Optimizing gas exchange, avoiding lung injury, and preserving respiratory muscle strength and endurance are vital therapeutic objectives for managing acute lung injury. Accordingly, comparing the physiology and consequences of breathing patterns that preserve and eliminate breathing effort has been a theme of persisting investigative interest throughout the several decades over which it has been possible to sustain cardiopulmonary life support outside the operating theater.

Identifying Risk for Acute Kidney Injury in Infants and Children Following Cardiac Arrest.

PubMed

Neumayr, Tara M; Gill, Jeff; Fitzgerald, Julie C; Gazit, Avihu Z; Pineda, Jose A; Berg, Robert A; Dean, J Michael; Moler, Frank W; Doctor, Allan

2017-10-01

Our goal was to identify risk factors for acute kidney injury in children surviving cardiac arrest. Retrospective analysis of a public access dataset. Fifteen children's hospitals associated with the Pediatric Emergency Care Applied Research Network. Two hundred ninety-six subjects between 1 day and 18 years old who experienced in-hospital or out-of-hospital cardiac arrest between July 1, 2003, and December 31, 2004. None. Our primary outcome was development of acute kidney injury as defined by the Acute Kidney Injury Network criteria. An ordinal probit model was developed. We found six critical explanatory variables, including total number of epinephrine doses, postcardiac arrest blood pressure, arrest location, presence of a chronic lung condition, pH, and presence of an abnormal baseline creatinine. Total number of epinephrine doses received as well as rate of epinephrine dosing impacted acute kidney injury risk and severity of acute kidney injury. This study is the first to identify risk factors for acute kidney injury in children after cardiac arrest. Our findings regarding the impact of epinephrine dosing are of particular interest and suggest potential for epinephrine toxicity with regard to acute kidney injury. The ability to identify and potentially modify risk factors for acute kidney injury after cardiac arrest may lead to improved morbidity and mortality in this population.

Elevated troponin I levels in acute liver failure: is myocardial injury an integral part of acute liver failure?

PubMed

Parekh, Nimisha K; Hynan, Linda S; De Lemos, James; Lee, William M

2007-06-01

Although rare instances of cardiac injury or arrhythmias have been reported in acute liver failure (ALF), overall, the heart is considered to be spared in this condition. Troponin I, a sensitive and specific marker of myocardial injury, may be elevated in patients with sepsis and acute stroke without underlying acute coronary syndrome, indicating unrecognized cardiac injury in these settings. We sought to determine whether subclinical cardiac injury might also occur in acute liver failure. Serum troponin I levels were measured in 187 patients enrolled in the US Acute Liver Failure Study Group registry, and correlated with clinical variables and outcomes. Diagnoses were representative of the larger group of >1000 patients thus far enrolled and included 80 with acetaminophen-related injury, 26 with viral hepatitis, 19 with ischemic injury, and 62 others. Overall, 74% of patients had elevated troponin I levels (>0.1 ng/ml). Patients with elevated troponin I levels were more likely to have advanced hepatic coma (grades III or IV) or to die (for troponin I levels >0.1 ng/ml, odds ratio 3.88 and 4.69 for advanced coma or death, respectively). In acute liver failure, subclinical myocardial injury appears to occur more commonly than has been recognized, and its pathogenesis in the context of acute liver failure is unclear. Elevated troponin levels are associated with a significant increase in morbidity and mortality. Measurement of troponin I levels may be helpful in patients with acute liver failure, to detect unrecognized myocardial damage and as a marker of unfavorable outcome.

Stem cells in sepsis and acute lung injury.

PubMed

Cribbs, Sushma K; Matthay, Michael A; Martin, Greg S

2010-12-01

Sepsis and acute lung injury continue to be major causes of morbidity and mortality worldwide despite advances in our understanding of pathophysiology and the discovery of new management strategies. Recent investigations show that stem cells may be beneficial as prognostic biomarkers and novel therapeutic strategies in these syndromes. This article reviews the potential use of endogenous adult tissue-derived stem cells in sepsis and acute lung injury as prognostic markers and also as exogenous cell-based therapy. A directed systematic search of the medical literature using PubMed and OVID, with particular emphasis on the time period after 2002, was done to evaluate topics related to 1) the epidemiology and pathophysiology of sepsis and acute lung injury; and 2) the definition, characterization, and potential use of stem cells in these diseases. DATA SYNTHESIS AND FINDINGS: When available, preferential consideration was given to prospective nonrandomized clinical and preclinical studies. Stem cells have shown significant promise in the field of critical care both for 1) prognostic value and 2) treatment strategies. Although several recent studies have identified the potential benefit of stem cells in sepsis and acute lung injury, further investigations are needed to more completely understand stem cells and their potential prognostic and therapeutic value.

Mesenchymal stem cells for acute lung injury: Preclinical evidence

PubMed Central

Matthay, Michael A.; Goolaerts, Arnaud; Howard, James P.; Lee, Jae Woo

2013-01-01

Several experimental studies have suggested that mesenchymal stem cells may have value for the treatment of clinical disorders, including myocardial infarction, diabetes, acute renal failure, sepsis, and acute lung injury. In preclinical studies, mesenchymal stem cells have been effective in reducing lung injury from endotoxin, live bacteria, bleomycin, and hyperoxia. In some studies, the cultured medium from mesenchymal stem cells has been as effective as the mesenchymal stem cells themselves. Several paracrine mediators that can mediate the effect of mesenchymal stem cells have been identified, including interleukin-10, interleukin-1ra, keratinocyte growth factor, and prostaglandin E2. Further preclinical studies are needed, as is planning for clinical trials for acute lung injury. PMID:21164399

Acute kidney injury in symptomatic primary Epstein-Barr virus infectious mononucleosis: Systematic review.

PubMed

Moretti, Milena; Lava, Sebastiano A G; Zgraggen, Lorenzo; Simonetti, Giacomo D; Kottanattu, Lisa; Bianchetti, Mario G; Milani, Gregorio P

2017-06-01

Textbooks and reviews do not mention the association of symptomatic primary Epstein-Barr virus infectious mononucleosis with acute kidney injury in subjects without immunodeficiency or autoimmunity. Stimulated by our experience with two cases, we performed a review of the literature. The literature documents 38 cases (26 male and 12 female individuals ranging in age from 0.3 to 51, median 18 years) of symptomatic primary Epstein-Barr virus infectious mononucleosis complicated by acute kidney injury: 27 acute interstitial nephritides, 1 jaundice-associated nephropathy, 7 myositides and 3 hemolytic uremic syndromes. Acute kidney injury requiring renal replacement therapy was observed in 18 (47%) cases. Acute kidney injury did not resolve in one patient with acute interstitial nephritis. Two patients died because of systemic complications. The remaining 35 cases fully recovered. In individuals with acute symptomatic Epstein-Barr virus infectious mononucleosis, a relevant kidney injury is rare but the outcome potentially fatal. It results from interstitial nephritis, myositis-associated acute kidney injury, hemolytic uremic syndrome or jaundice-associated nephropathy. Copyright © 2017 Elsevier B.V. All rights reserved.

Rhabdomyolysis and acute kidney injury in patients with traumatic spinal cord injury

PubMed Central

Galeiras, Rita; Mourelo, Mónica; Pértega, Sonia; Lista, Amanda; Ferreiro, Mª Elena; Salvador, Sebastián; Montoto, Antonio; Rodríguez, Antonio

2016-01-01

Background: Patients with acute traumatic spinal cord injuries (SCIs) exhibit factors that, in other populations, have been associated with rhabdomyolysis. Purpose: The aim of the study is to determine the incidence of rhabdomyolysis in patients with acute traumatic SCI admitted to the Intensive Care Unit (ICU), as well as the development of secondary acute kidney injury and associated factors. Study Design and Setting: This was an observational, retrospective study. Patient Sample: All adult patients admitted to the ICU with acute traumatic SCI who presented rhabdomyolysis, diagnosed through creatine phosphokinase (CPK) levels >500 IU/L. Outcome Measures: Incidence of rhabdomyolysis and subsequent renal dysfunction was calculated. Materials and Methods: Data about demographic variables, comorbidity, rhabdomyolysis risk factors, and variables involving SCI, severity scores, and laboratory parameters were obtained from clinical records. Multivariate logistic regression was used to identify renal injury risk factors. Results: In 2006–2014, 200 patients with acute SCI were admitted to ICU. Of these, 103 had rhabdomyolysis (incidence = 51.5%; 95% confidence interval [CI]: 44.3%–58.7%). The most typical American Spinal Injury Association classification was A (70.3%). The injury severity score was 30.3 ± 12.1 and sequential organ failure assessment (SOFA) score was 5.6 ± 3.3 points. During their stay, 57 patients (55.3%; 95% CI: 45.2%–65.4%) presented renal dysfunction (creatinine ≥1.2 mg/dL). In the multivariate analysis, variables associated with renal dysfunction were creatinine at admission (odds ratio [OR] = 9.20; P = 0.006) and hemodynamic SOFA score the day following admission (OR = 1.33; P = 0.024). Creatinine was a better predictor of renal dysfunction than the peak CPK value during the rhabdomyolysis (area under the receiver operating characteristic curve: 0.91 vs. 0.63, respectively). Conclusions: Rhabdomyolysis is a frequent condition in patients

Type XVIII collagen degradation products in acute lung injury

PubMed Central

Perkins, Gavin D; Nathani, Nazim; Richter, Alex G; Park, Daniel; Shyamsundar, Murali; Heljasvaara, Ritva; Pihlajaniemi, Taina; Manji, Mav; Tunnicliffe, W; McAuley, Danny; Gao, Fang; Thickett, David R

2009-01-01

Introduction In acute lung injury, repair of the damaged alveolar-capillary barrier is an essential part of recovery. Endostatin is a 20 to 28 kDa proteolytic fragment of the basement membrane collagen XVIII, which has been shown to inhibit angiogenesis via action on endothelial cells. We hypothesised that endostatin may have a role in inhibiting lung repair in patients with lung injury. The aims of the study were to determine if endostatin is elevated in the plasma/bronchoalveolar lavage fluid of patients with acute lung injury and ascertain whether the levels reflect the severity of injury and alveolar inflammation, and to assess if endostatin changes occur early after the injurious lung stimuli of one lung ventilation and lipopolysaccharide (LPS) challenge. Methods Endostatin was measured by ELISA and western blotting. Results Endostatin is elevated within the plasma and bronchoalveolar lavage fluid of patients with acute lung injury. Lavage endostatin reflected the degree of alveolar neutrophilia and the extent of the loss of protein selectivity of the alveolar-capillary barrier. Plasma levels of endostatin correlated with the severity of physiological derangement. Western blotting confirmed elevated type XVIII collagen precursor levels in the plasma and lavage and multiple endostatin-like fragments in the lavage of patients. One lung ventilation and LPS challenge rapidly induce increases in lung endostatin levels. Conclusions Endostatin may adversely affect both alveolar barrier endothelial and epithelial cells, so its presence within both the circulation and the lung may have a pathophysiological role in acute lung injury that warrants further evaluation. PMID:19358707

Data on necrotic and apoptotic cell death in acute myocardial ischemia/reperfusion injury: the effects of CaMKII and angiotensin AT1 receptor inhibition.

PubMed

Rajtik, Tomas; Carnicka, Slavka; Szobi, Adrian; Giricz, Zoltan; O-Uchi, Jin; Hassova, Veronika; Svec, Pavel; Ferdinandy, Peter; Ravingerova, Tanya; Adameova, Adriana

2016-06-01

Content of particular proteins indicating cellular injury due to apoptosis and necrosis has been investigated in ischemic/reperfused (IR) hearts and ischemic/reperfused hearts treated with CaMKII inhibitor and/or AT1 receptor inhibitor. This data article provides information in support of the original research article "Oxidative activation of CaMKIIδ in acute myocardial ischemia/reperfusion injury: a role of angiotensin AT1 receptor-NOX2 signaling axis" [1].

Acute respiratory distress syndrome and acute lung injury.

PubMed

Dushianthan, A; Grocott, M P W; Postle, A D; Cusack, R

2011-09-01

Acute respiratory distress syndrome (ARDS) is a life threatening respiratory failure due to lung injury from a variety of precipitants. Pathologically ARDS is characterised by diffuse alveolar damage, alveolar capillary leakage, and protein rich pulmonary oedema leading to the clinical manifestation of poor lung compliance, severe hypoxaemia, and bilateral infiltrates on chest radiograph. Several aetiological factors associated with the development of ARDS are identified with sepsis, pneumonia, and trauma with multiple transfusions accounting for most cases. Despite the absence of a robust diagnostic definition, extensive epidemiological investigations suggest ARDS remains a significant health burden with substantial morbidity and mortality. Improvements in outcome following ARDS over the past decade are in part due to improved strategies of mechanical ventilation and advanced support of other failing organs. Optimal treatment involves judicious fluid management, protective lung ventilation with low tidal volumes and moderate positive end expiratory pressure, multi-organ support, and treatment where possible of the underlying cause. Moreover, advances in general supportive measures such as appropriate antimicrobial therapy, early enteral nutrition, prophylaxis against venous thromboembolism and gastrointestinal ulceration are likely contributory reasons for the improved outcomes. Although therapies such as corticosteroids, nitric oxide, prostacyclins, exogenous surfactants, ketoconazole and antioxidants have shown promising clinical effects in animal models, these have failed to translate positively in human studies. Most recently, clinical trials with β2 agonists aiding alveolar fluid clearance and immunonutrition with omega-3 fatty acids have also provided disappointing results. Despite these negative studies, mortality seems to be in decline due to advances in overall patient care. Future directions of research are likely to concentrate on identifying potential

Cellular Therapy for Chronic Traumatic Brachial Plexus Injury

PubMed Central

Sharma, Alok; Sane, Hemangi; Gokulchandran, Nandini; Badhe, Prerna; Pai, Suhasini; Kulkarni, Pooja; Yadav, Jayanti; Inamdar, Sanket

2018-01-01

Cellular therapy is being actively pursued as a therapeutic modality in many of the neurological diseases. A variety of stem cells from diverse sources have been studied in detail and have been shown to exhibit angiogenetic and immunomodulatory properties in addition to other neuroprotective effects. Published clinical data have shown bone marrow mononuclear cell (BMMNC) injection in neurological disorders is safe and possesses regenerative potential. We illustrate a case of 27-year-old male with traumatic brachial plexus injury, administered with autologous BMMNCs intrathecally and intramuscularly, followed by multidisciplinary rehabilitation. At the follow-up assessment of 3 and 7 months after first cell transplantation, improvements were recorded in muscle strength and movements. Electromyography (EMG) performed after the intervention showed a response in biceps and deltoid muscles suggesting the process of reinnervation at the site of injury. In view of the improvements observed after the treatment, the patient underwent second cell transplantation 8 months after the first transplantation. Muscle wasting had completely stopped with an increase in the muscle girth. No adverse effects were noted. Improvements were maintained for 4 years. A comprehensive randomized study for this type of injury is needed to establish the therapeutic benefits of cellular therapy. PMID:29657936

Nonlinear Dynamic Theory of Acute Cell Injuries and Brain Ischemia

NASA Astrophysics Data System (ADS)

Taha, Doaa; Anggraini, Fika; Degracia, Donald; Huang, Zhi-Feng

2015-03-01

Cerebral ischemia in the form of stroke and cardiac arrest brain damage affect over 1 million people per year in the USA alone. In spite of close to 200 clinical trials and decades of research, there are no treatments to stop post-ischemic neuron death. We have argued that a major weakness of current brain ischemia research is lack of a deductive theoretical framework of acute cell injury to guide empirical studies. A previously published autonomous model based on the concept of nonlinear dynamic network was shown to capture important facets of cell injury, linking the concept of therapeutic to bistable dynamics. Here we present an improved, non-autonomous formulation of the nonlinear dynamic model of cell injury that allows multiple acute injuries over time, thereby allowing simulations of both therapeutic treatment and preconditioning. Our results are connected to the experimental data of gene expression and proteomics of neuron cells. Importantly, this new model may be construed as a novel approach to pharmacodynamics of acute cell injury. The model makes explicit that any pro-survival therapy is always a form of sub-lethal injury. This insight is expected to widely influence treatment of acute injury conditions that have defied successful treatment to date. This work is supported by NIH NINDS (NS081347) and Wayne State University President's Research Enhancement Award.

Risk of Acute Kidney Injury After Intravenous Contrast Media Administration.

PubMed

Hinson, Jeremiah S; Ehmann, Michael R; Fine, Derek M; Fishman, Elliot K; Toerper, Matthew F; Rothman, Richard E; Klein, Eili Y

2017-05-01

The study objective was to determine whether intravenous contrast administration for computed tomography (CT) is independently associated with increased risk for acute kidney injury and adverse clinical outcomes. This single-center retrospective cohort analysis was performed in a large, urban, academic emergency department with an average census of 62,179 visits per year; 17,934 ED visits for patients who underwent contrast-enhanced, unenhanced, or no CT during a 5-year period (2009 to 2014) were included. The intervention was CT scan with or without intravenous contrast administration. The primary outcome was incidence of acute kidney injury. Secondary outcomes included new chronic kidney disease, dialysis, and renal transplantation at 6 months. Logistic regression modeling and between-groups odds ratios with and without propensity-score matching were used to test for an independent association between contrast administration and primary and secondary outcomes. Treatment decisions, including administration of contrast and intravenous fluids, were examined. Rates of acute kidney injury were similar among all groups. Contrast administration was not associated with increased incidence of acute kidney injury (contrast-induced nephropathy criteria odds ratio=0.96, 95% confidence interval 0.85 to 1.08; and Acute Kidney Injury Network/Kidney Disease Improving Global Outcomes criteria odds ratio=1.00, 95% confidence interval 0.87 to 1.16). This was true in all subgroup analyses regardless of baseline renal function and whether comparisons were made directly or after propensity matching. Contrast administration was not associated with increased incidence of chronic kidney disease, dialysis, or renal transplant at 6 months. Clinicians were less likely to prescribe contrast to patients with decreased renal function and more likely to prescribe intravenous fluids if contrast was administered. In the largest well-controlled study of acute kidney injury following contrast

Surfactant for Pediatric Acute Lung Injury

PubMed Central

Willson, Douglas F.; Chess, Patricia R.; Notter, Robert H.

2008-01-01

Synopsis This article reviews exogenous surfactant therapy and its use in mitigating acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) in infants, children, and adults. Biophysical and animal research documenting surfactant dysfunction in ALI/ARDS is described, and the scientific rationale for treatment with exogenous surfactant is discussed. Major emphasis is on reviewing clinical studies of surfactant therapy in pediatric and adult patients with ALI/ARDS. Particular advantages from surfactant therapy in direct pulmonary forms of these syndromes are described. Also discussed are additional factors affecting the efficacy of exogenous surfactants in ALI/ARDS, including the multifaceted pathology of inflammatory lung injury, the effectiveness of surfactant delivery in injured lungs, and composition-based activity differences among clinical exogenous surfactant preparations. PMID:18501754

Role of Nrf2 and Autophagy in Acute Lung Injury

PubMed Central

Rojo de la Vega, Montserrat; Dodson, Matthew; Gross, Christine; Manzour, Heidi; Lantz, R. Clark; Chapman, Eli; Wang, Ting; Black, Stephen M.; Garcia, Joe G.N.; Zhang, Donna D.

2016-01-01

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the clinical manifestations of severe lung damage and respiratory failure. Characterized by severe inflammation and compromised lung function, ALI/ARDS result in very high mortality of affected individuals. Currently, there are no effective treatments for ALI/ARDS, and ironically, therapies intended to aid patients (specifically mechanical ventilation, MV) may aggravate the symptoms. Key events contributing to the development of ALI/ARDS are: increased oxidative and proteotoxic stresses, unresolved inflammation, and compromised alveolar-capillary barrier function. Since the airways and lung tissues are constantly exposed to gaseous oxygen and airborne toxicants, the bronchial and alveolar epithelial cells are under higher oxidative stress than other tissues. Cellular protection against oxidative stress and xenobiotics is mainly conferred by Nrf2, a transcription factor that promotes the expression of genes that regulate oxidative stress, xenobiotic metabolism and excretion, inflammation, apoptosis, autophagy, and cellular bioenergetics. Numerous studies have demonstrated the importance of Nrf2 activation in the protection against ALI/ARDS, as pharmacological activation of Nrf2 prevents the occurrence or mitigates the severity of ALI/ARDS. Another promising new therapeutic strategy in the prevention and treatment of ALI/ARDS is the activation of autophagy, a bulk protein and organelle degradation pathway. In this review, we will discuss the strategy of concerted activation of Nrf2 and autophagy as a preventive and therapeutic intervention to ameliorate ALI/ARDS. PMID:27313980

Abstraction and Idealization in Biomedicine: The Nonautonomous Theory of Acute Cell Injury.

PubMed

DeGracia, Donald J; Taha, Doaa; Tri Anggraini, Fika; Sutariya, Shreya; Rababeh, Gabriel; Huang, Zhi-Feng

2018-02-27

Neuroprotection seeks to halt cell death after brain ischemia and has been shown to be possible in laboratory studies. However, neuroprotection has not been successfully translated into clinical practice, despite voluminous research and controlled clinical trials. We suggested these failures may be due, at least in part, to the lack of a general theory of cell injury to guide research into specific injuries. The nonlinear dynamical theory of acute cell injury was introduced to ameliorate this situation. Here we present a revised nonautonomous nonlinear theory of acute cell injury and show how to interpret its solutions in terms of acute biomedical injuries. The theory solutions demonstrate the complexity of possible outcomes following an idealized acute injury and indicate that a "one size fits all" therapy is unlikely to be successful. This conclusion is offset by the fact that the theory can (1) determine if a cell has the possibility to survive given a specific acute injury, and (2) calculate the degree of therapy needed to cause survival. To appreciate these conclusions, it is necessary to idealize and abstract complex physical systems to identify the fundamental mechanism governing the injury dynamics. The path of abstraction and idealization in biomedical research opens the possibility for medical treatments that may achieve engineering levels of precision.

Abstraction and Idealization in Biomedicine: The Nonautonomous Theory of Acute Cell Injury

PubMed Central

DeGracia, Donald J.; Taha, Doaa; Tri Anggraini, Fika; Sutariya, Shreya; Rababeh, Gabriel; Huang, Zhi-Feng

2018-01-01

Neuroprotection seeks to halt cell death after brain ischemia and has been shown to be possible in laboratory studies. However, neuroprotection has not been successfully translated into clinical practice, despite voluminous research and controlled clinical trials. We suggested these failures may be due, at least in part, to the lack of a general theory of cell injury to guide research into specific injuries. The nonlinear dynamical theory of acute cell injury was introduced to ameliorate this situation. Here we present a revised nonautonomous nonlinear theory of acute cell injury and show how to interpret its solutions in terms of acute biomedical injuries. The theory solutions demonstrate the complexity of possible outcomes following an idealized acute injury and indicate that a “one size fits all” therapy is unlikely to be successful. This conclusion is offset by the fact that the theory can (1) determine if a cell has the possibility to survive given a specific acute injury, and (2) calculate the degree of therapy needed to cause survival. To appreciate these conclusions, it is necessary to idealize and abstract complex physical systems to identify the fundamental mechanism governing the injury dynamics. The path of abstraction and idealization in biomedical research opens the possibility for medical treatments that may achieve engineering levels of precision. PMID:29495539

Multiphoton imaging for assessing renal disposition in acute kidney injury

NASA Astrophysics Data System (ADS)

Liu, Xin; Liang, Xiaowen; Wang, Haolu; Roberts, Darren M.; Roberts, Michael S.

2016-11-01

Estimation of renal function and drug renal disposition in acute kidney injury (AKI), is important for appropriate dosing of drugs and adjustment of therapeutic strategies, but is challenging due to fluctuations in kidney function. Multiphoton microscopy has been shown to be a useful tool in studying drug disposition in liver and can reflect dynamic changes of liver function. We extend this imaging technique to investigate glomerular filtration rate (GFR) and tubular transporter functional change in various animal models of AKI, which mimic a broad range of causes of AKI such as hypoxia (renal ischemia- reperfusion), therapeutic drugs (e.g. cisplatin), rhabdomyolysis (e.g. glycerol-induced) and sepsis (e.g. LPSinduced). The MPM images revealed acute injury of tubular cells as indicated by reduced autofluorescence and cellular vacuolation in AKI groups compared to control group. In control animal, systemically injected FITC-labelled inulin was rapidly cleared from glomerulus, while the clearance of FITC-inulin was significantly delayed in most of animals in AKI group, which may reflect the reduced GFR in AKI. Following intravenous injection, rhodamine 123, a fluorescent substrate of p-glycoprotein (one of tubular transporter), was excreted into urine in proximal tubule via p-glycoprotein; in response to AKI, rhodamine 123 was retained in tubular cells as revealed by slower decay of fluorescence intensity, indicating P-gp transporter dysfunction in AKI. Thus, real-time changes in GFR and transporter function can be imaged in rodent kidney with AKI using multiphoton excitation of exogenously injected fluorescent markers.

Sepsis and Acute Kidney Injury.

PubMed

Bilgili, Beliz; Haliloğlu, Murat; Cinel, İsmail

2014-12-01

Acute kindney injury (AKI) is a clinical syndrome which is generally defined as an abrupt decline in glomerular filtration rate, causing accumulation of nitrogenous products and rapid development of fluid, electrolyte and acid base disorders. In intensive care unit sepsis and septic shock are leading causes of AKI. Sepsis-induced AKI literally acts as a biologic indicator of clinical deterioration. AKI triggers variety of immune, inflammatory, metabolic and humoral patways; ultimately leading distant organ dysfunction and increases morbidity and mortality. Serial mesurements of creatinine and urine volume do not make it possible to diagnose AKI at early stages. Serum creatinine influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reason we need new markers, and many biomarkers in the diagnosis of early AKI activity is assessed. Historically "Risk-Injury-Failure-Loss-Endstage" (RIFLE), "Acute Kidney Injury Netwok" (AKIN) and "The Kidney Disease/ Improving Global Outcomes" (KDIGO) classification systems are used for diagnosing easily in clinical practice and research and grading disease. Classifications including diagnostic criteria are formed for the identification of AKI. Neutrophil gelatinase associated lipocalin (NGAL), cystatin-C (Cys-C), kidney injury molecule-1 (KIM-1) and also "cell cycle arrest" molecules has been concerned for clinical use. In this review the pathophysiology of AKI, with the relationship of sepsis and the importance of early diagnosis of AKI is evaluated.

Acute Kidney Injury in Pediatric Severe Sepsis: An Independent Risk Factor for Death and New Disability.

PubMed

Fitzgerald, Julie C; Basu, Rajit K; Akcan-Arikan, Ayse; Izquierdo, Ledys M; Piñeres Olave, Byron E; Hassinger, Amanda B; Szczepanska, Maria; Deep, Akash; Williams, Duane; Sapru, Anil; Roy, Jason A; Nadkarni, Vinay M; Thomas, Neal J; Weiss, Scott L; Furth, Susan

2016-12-01

The prevalence of septic acute kidney injury and impact on functional status of PICU survivors are unknown. We used data from an international prospective severe sepsis study to elucidate functional outcomes of children suffering septic acute kidney injury. Secondary analysis of patients in the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study: acute kidney injury was defined on the study day using Kidney Disease Improving Global Outcomes definitions. Patients with no acute kidney injury or stage 1 acute kidney injury ("no/mild acute kidney injury") were compared with those with stage 2 or 3 acute kidney injury ("severe acute kidney injury"). The primary outcome was a composite of death or new moderate disability at discharge defined as a Pediatric Overall Performance Category score of 3 or higher and increased by 1 from baseline. One hundred twenty-eight PICUs in 26 countries. Children with severe sepsis in the Sepsis PRevalence, OUtcomes, and Therapies study. None. One hundred two (21%) of 493 patients had severe acute kidney injury. More than twice as many patients with severe acute kidney injury died or developed new moderate disability compared with those with no/mild acute kidney injury (64% vs 30%; p < 0.001). Severe acute kidney injury was independently associated with death or new moderate disability (adjusted odds ratio, 2.5; 95% CI, 1.5-4.2; p = 0.001) after adjustment for age, region, baseline disability, malignancy, invasive mechanical ventilation, albumin administration, and the pediatric logistic organ dysfunction score. In a multinational cohort of critically ill children with severe sepsis and high mortality rates, septic acute kidney injury is independently associated with further increased death or new disability.

Pharmacotherapy of Acute Lung Injury and Acute Respiratory Distress Syndrome

PubMed Central

Raghavendran, Krishnan; Pryhuber, Gloria S.; Chess, Patricia R.; Davidson, Bruce A.; Knight, Paul R.; Notter, Robert H.

2009-01-01

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are characterized by rapid-onset respiratory failure following a variety of direct and indirect insults to the parenchyma or vasculature of the lungs. Mortality from ALI/ARDS is substantial, and current therapy primarily emphasizes mechanical ventilation and judicial fluid management plus standard treatment of the initiating insult and any known underlying disease. Current pharmacotherapy for ALI/ARDS is not optimal, and there is a significant need for more effective medicinal chemical agents for use in these severe and lethal lung injury syndromes. To facilitate future chemical-based drug discovery research on new agent development, this paper reviews present pharmacotherapy for ALI/ARDS in the context of biological and biochemical drug activities. The complex lung injury pathophysiology of ALI/ARDS offers an array of possible targets for drug therapy, including inflammation, cell and tissue injury, vascular dysfunction, surfactant dysfunction, and oxidant injury. Added targets for pharmacotherapy outside the lungs may also be present, since multiorgan or systemic pathology is common in ALI/ARDS. The biological and physiological complexity of ALI/ARDS requires the consideration of combined-agent treatments in addition to single-agent therapies. A number of pharmacologic agents have been studied individually in ALI/ARDS, with limited or minimal success in improving survival. However, many of these agents have complementary biological/biochemical activities with the potential for synergy or additivity in combination therapy as discussed in this article. PMID:18691048

Exertion and acute coronary artery injury.

PubMed

Black, A; Black, M M; Gensini, G

1975-12-01

Twelve cases of myocardial infarction as related to strenuous exertion are presented with the pathological findings in several of these cases. Three cases with coronary arteriography are also presented. The pathology of coronary arteriosclerotic plaques and the vulnerability to acute injury is reviewed and discussed. It is concluded that strenuous exertion can cause acute injury to coronary artery plaques due to the unusual stressful whip-like action to which coronary arteries are subject. These injuries may initiate as cracks in the plaques or subintimal hemorrhages and proceed to coronary occlusion and ultimate myocardial infarction. With this concept in mind we use the term of "crack in the plaque" (Black's Crack in the Plaque) to account for the sudden appearance of clinical coronary artery disease appearing during or shortly after exertion, or other stressful situations in patients without previous existing evidence of clinical coronary artery disease. This could also account for exacerbation of symptoms or death occurring after exertion in previously quiescent asymptomatic known coronary artery disease subjects. This concept may explain some of the puzzling features of coronary disease.

Pathophysiology of Cisplatin-Induced Acute Kidney Injury

PubMed Central

Ozkok, Abdullah; Edelstein, Charles L.

2014-01-01

Cisplatin and other platinum derivatives are the most widely used chemotherapeutic agents to treat solid tumors including ovarian, head and neck, and testicular germ cell tumors. A known complication of cisplatin administration is acute kidney injury (AKI). The nephrotoxic effect of cisplatin is cumulative and dose-dependent and often necessitates dose reduction or withdrawal. Recurrent episodes of AKI may result in chronic kidney disease. The pathophysiology of cisplatin-induced AKI involves proximal tubular injury, oxidative stress, inflammation, and vascular injury in the kidney. There is predominantly acute tubular necrosis and also apoptosis in the proximal tubules. There is activation of multiple proinflammatory cytokines and infiltration of inflammatory cells in the kidney. Inhibition of the proinflammatory cytokines TNF-α or IL-33 or depletion of CD4+ T cells or mast cells protects against cisplatin-induced AKI. Cisplatin also causes endothelial cell injury. An understanding of the pathogenesis of cisplatin-induced AKI is important for the development of adjunctive therapies to prevent AKI, to lessen the need for dose decrease or drug withdrawal, and to lessen patient morbidity and mortality. PMID:25165721

Predicting kidney disease progression in patients with acute kidney injury after cardiac surgery.

PubMed

Mizuguchi, K Annette; Huang, Chuan-Chin; Shempp, Ian; Wang, Justin; Shekar, Prem; Frendl, Gyorgy

2018-06-01

The study objective was to identify patients who are likely to develop progressive kidney dysfunction (acute kidney disease) before their hospital discharge after cardiac surgery, allowing targeted monitoring of kidney function in this at-risk group with periodic serum creatinine measurements. Risks of progression to acute kidney disease (a state in between acute kidney injury and chronic kidney disease) were modeled from acute kidney injury stages (Kidney Disease: Improving Global Outcomes) in patients undergoing cardiac surgery. A modified Poisson regression with robust error variance was used to evaluate the association between acute kidney injury stages and the development of acute kidney disease (defined as doubling of creatinine 2-4 weeks after surgery) in this observational study. Acute kidney disease occurred in 4.4% of patients with no preexisting kidney disease and 4.8% of patients with preexisting chronic kidney disease. Acute kidney injury predicted development of acute kidney disease in a graded manner in which higher stages of acute kidney injury predicted higher relative risk of progressive kidney disease (area under the receiver operator characteristic curve = 0.82). This correlation persisted regardless of baseline kidney function (P < .001). Of note, development of acute kidney disease was associated with higher mortality and need for renal replacement therapy. The degree of acute kidney injury can identify patients who will have a higher risk of progression to acute kidney disease. These patients may benefit from close follow-up of renal function because they are at risk of progressing to chronic kidney disease or end-stage renal disease. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Protective effects of Tribulus terrestris L extract against acute kidney injury induced by reperfusion injury in rats.

PubMed

Najafi, Houshang; Firouzifar, Mohammad Reza; Shafaat, Omid; Changizi Ashtiyani, Saeed; Hosseini, Nasser

2014-07-01

This study aimed to investigate the protective effect of aerial parts of the Tribulus terrestris L extract on acute kidney injury (AKI) induced by ischemia for 30 minutes and reperfusion for 24 hours in rats. Ten male Sprague-Dawley rats in the AKI and 10 in the Tribulus terrestris groups received the extract solvent and extract of the plant (11 mg/kg), respectively, for 13 days (oral administration). On day 14, ischemia for 30 minutes and reperfusion for 24 hours were induced on the rats. In the last 6 hours of the reperfusion period (24 hours), urine samples were collected in metabolic cages. At the end of this period, blood samples were also taken to determine plasma urea nitrogen, creatinine, and electrolyte concentrations. The kidney tissues were collected for measuring the level of oxidative stress and histological studies. They were compared with the sham operation group and a control group with normal diet and no operation. In the Tribulus terrestris group, the increase in plasma creatinine and urea nitrogen concentrations was significantly less following reperfusion, and their values reached the same level as that in the sham group. Creatinine clearance and urine osmolarity in the Tribulus terrestris group was higher in comparison with the AKI group, whereas sodium absolute excretion, fractional excretion of potassium, oxidative stress, and cellular damages were less. Oral administration of Tribulus terrestris extract for 2 weeks can decrease kidney functional disturbance, oxidative stress, and cellular damages following reperfusion injury in rats.

Therapeutic Potential of Intravenous Immunoglobulin in Acute Brain Injury

PubMed Central

Thom, Vivien; Arumugam, Thiruma V.; Magnus, Tim; Gelderblom, Mathias

2017-01-01

Acute ischemic and traumatic injury of the central nervous system (CNS) is known to induce a cascade of inflammatory events that lead to secondary tissue damage. In particular, the sterile inflammatory response in stroke has been intensively investigated in the last decade, and numerous experimental studies demonstrated the neuroprotective potential of a targeted modulation of the immune system. Among the investigated immunomodulatory agents, intravenous immunoglobulin (IVIg) stand out due to their beneficial therapeutic potential in experimental stroke as well as several other experimental models of acute brain injuries, which are characterized by a rapidly evolving sterile inflammatory response, e.g., trauma, subarachnoid hemorrhage. IVIg are therapeutic preparations of polyclonal immunoglobulin G, extracted from the plasma of thousands of donors. In clinical practice, IVIg are the treatment of choice for diverse autoimmune diseases and various mechanisms of action have been proposed. Only recently, several experimental studies implicated a therapeutic potential of IVIg even in models of acute CNS injury, and suggested that the immune system as well as neuronal cells can directly be targeted by IVIg. This review gives further insight into the role of secondary inflammation in acute brain injury with an emphasis on stroke and investigates the therapeutic potential of IVIg. PMID:28824617

The Development of a Machine Learning Inpatient Acute Kidney Injury Prediction Model.

PubMed

Koyner, Jay L; Carey, Kyle A; Edelson, Dana P; Churpek, Matthew M

2018-07-01

To develop an acute kidney injury risk prediction model using electronic health record data for longitudinal use in hospitalized patients. Observational cohort study. Tertiary, urban, academic medical center from November 2008 to January 2016. All adult inpatients without pre-existing renal failure at admission, defined as first serum creatinine greater than or equal to 3.0 mg/dL, International Classification of Diseases, 9th Edition, code for chronic kidney disease stage 4 or higher or having received renal replacement therapy within 48 hours of first serum creatinine measurement. None. Demographics, vital signs, diagnostics, and interventions were used in a Gradient Boosting Machine algorithm to predict serum creatinine-based Kidney Disease Improving Global Outcomes stage 2 acute kidney injury, with 60% of the data used for derivation and 40% for validation. Area under the receiver operator characteristic curve (AUC) was calculated in the validation cohort, and subgroup analyses were conducted across admission serum creatinine, acute kidney injury severity, and hospital location. Among the 121,158 included patients, 17,482 (14.4%) developed any Kidney Disease Improving Global Outcomes acute kidney injury, with 4,251 (3.5%) developing stage 2. The AUC (95% CI) was 0.90 (0.90-0.90) for predicting stage 2 acute kidney injury within 24 hours and 0.87 (0.87-0.87) within 48 hours. The AUC was 0.96 (0.96-0.96) for receipt of renal replacement therapy (n = 821) in the next 48 hours. Accuracy was similar across hospital settings (ICU, wards, and emergency department) and admitting serum creatinine groupings. At a probability threshold of greater than or equal to 0.022, the algorithm had a sensitivity of 84% and a specificity of 85% for stage 2 acute kidney injury and predicted the development of stage 2 a median of 41 hours (interquartile range, 12-141 hr) prior to the development of stage 2 acute kidney injury. Readily available electronic health record data can be

Mechanistic insights of sulfur mustard-induced acute tracheal injury in rats.

PubMed

Zhu, Xiao-Ji; Xu, Rui; Meng, Xiao; Chu, Hai-Bo; Zhao, Chao; Lian, Cheng-Jin; Wang, Tao; Guo, Wen-Jun; Zhang, Sheng-Ming

2014-01-01

Sulfur mustard (SM) is believed to be a major threat to civilian populations because of the persistent asymmetric threat by nonstate actors, such as terrorist groups, the ease of synthesis and handling, and the risk of theft from stockpiles. The purpose of this study was to establish mechanisms of acute tracheal injury in rats induced by SM using histopathologic, immunohistochemical, and biochemical parameters. Male rats (Sprague-Dawley) were anesthetized, intratracheally intubated, and exposed to 2 mg/kg of SM. Animals were euthanized 6-, 24-, 48-, and 72-hour postexposure, and intracavitary blood samples from the heart and tracheal tissues were collected. Exposure of rats to SM resulted in rapid tracheal injury, including tracheal epithelial cell shedding, focal ulceration, and abundant lymphocyte invasion of the submucosa. There was also evidence of a large number of apoptotic cells in the epithelium and submucosa, the serum levels of tumor necrosis factor α, interleukin 1β (IL) 1β, IL-6, and γ-glutamyl transferase peaked at 24 hours, and the serum levels of lactate dehydrogenase, glutathione peroxidase, and thiobarbituric acid reactive substance peaked at 6 hours. The SM exposure also resulted in a loss of the cellular membrane, leakage of cytoplasm, fuzzy mitochondrial cristae, medullary changes in ciliated and goblet cells, and the nuclear chromatin appeared marginated in basal cells and fibroblasts. The results in the propylene glycol group were the same as the control group. These data demonstrated the histologic changes, inflammatory reactions, apoptosis, oxidative stress, and DNA damage following SM (2 mg/kg)-induced acute tracheal injury; the severity of changes was time dependent. © The Author(s) 2014.

Fluid accumulation during acute kidney injury in the intensive care unit.

PubMed

Berthelsen, R E; Perner, A; Jensen, A K; Jensen, J-U; Bestle, M H

2018-07-01

Fluid therapy is a ubiquitous intervention in patients admitted to the intensive care unit, but positive fluid balance may be associated with poor outcomes and particular in patients with acute kidney injury. Studies describing this have defined fluid overload either at specific time points or considered patients with a positive mean daily fluid balance as fluid overloaded. We wished to detail this further and performed joint model analyses of the association between daily fluid balance and outcome represented by mortality and renal recovery in patients admitted with acute kidney injury. We did a retrospective cohort study of patients admitted to the intensive care unit with acute kidney injury during a 2-year observation period. We used serum creatinine measurements to identify patients with acute kidney injury and collected sequential daily fluid balance during the first 5 days of admission to the intensive care unit. We used joint modelling techniques to correlate the development of fluid overload with survival and renal recovery adjusted for age, gender and disease severity. The cohort contained 863 patients with acute kidney injury of whom 460 (53%) and 254 (29%) developed 5% and 10% fluid overload, respectively. We found that both 5% and 10% fluid overload was correlated with reduced survival and renal recovery. Joint model analyses of fluid accumulation in patients admitted to the intensive care unit with acute kidney injury confirm that even a modest degree of fluid overload (5%) may be negatively associated with both survival and renal recovery. © 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Obeticholic acid protects against carbon tetrachloride-induced acute liver injury and inflammation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Da-Gang

The farnesoid X receptor (FXR) is a ligand-activated transcription factor that plays important roles in regulating bile acid homeostasis. The aim of the present study was to investigate the effects of obeticholic acid (OCA), a novel synthetic FXR agonist, carbon tetrachloride (CCl{sub 4})-induced acute liver injury. Mice were intraperitoneally injected with CCl{sub 4} (0.15 ml/kg). In CCl{sub 4} + OCA group, mice were orally with OCA (5 mg/kg) 48, 24 and 1 h before CCl{sub 4}. As expected, hepatic FXR was activated by OCA. Interestingly, OCA pretreatment alleviated CCl{sub 4}-induced elevation of serum ALT and hepatic necrosis. Moreover, OCA pretreatmentmore » inhibited CCl{sub 4}-induced hepatocyte apoptosis. Additional experiment showed that OCA inhibits CCl{sub 4}-induced hepatic chemokine gene Mcp-1, Mip-2 and Kc. Moreover, OCA inhibits CCl{sub 4}-induced hepatic pro-inflammatory gene Tnf-α and Il-1β. By contrast, OCA pretreatment elevated hepatic anti-inflammatory gene Il-4. Further analysis showed that OCA pretreatment inhibited hepatic IκB phosphorylation and blocked nuclear translocation of NF-κB p65 and p50 subunits during CCl{sub 4}-induced acute liver injury. In addition, OCA pretreatment inhibited hepatic Akt, ERK and p38 phosphorylation in CCl{sub 4}-induced acute liver injury. These results suggest that OCA protects against CCl{sub 4}-induced acute liver injury and inflammation. Synthetic FXR agonists may be effective antidotes for hepatic inflammation during acute liver injury. - Highlights: • OCA pretreatment activates hepatic FXR. • FXR activation protects against CCl{sub 4}-induced acute liver injury. • FXR activation inhibits hepatocyte apoptosis during CCl{sub 4}-induced liver injury. • FXR activation differentially regulates hepatic inflammatory genes. • Synthetic FXR agonists are effective antidotes for acute liver injury.« less

Acetazolamide Mitigates Astrocyte Cellular Edema Following Mild Traumatic Brain Injury

NASA Astrophysics Data System (ADS)

Sturdivant, Nasya M.; Smith, Sean G.; Ali, Syed F.; Wolchok, Jeffrey C.; Balachandran, Kartik

2016-09-01

Non-penetrating or mild traumatic brain injury (mTBI) is commonly experienced in accidents, the battlefield and in full-contact sports. Astrocyte cellular edema is one of the major factors that leads to high morbidity post-mTBI. Various studies have reported an upregulation of aquaporin-4 (AQP4), a water channel protein, following brain injury. AZA is an antiepileptic drug that has been shown to inhibit AQP4 expression and in this study we investigate the drug as a therapeutic to mitigate the extent of mTBI induced cellular edema. We hypothesized that mTBI-mediated astrocyte dysfunction, initiated by increased intracellular volume, could be reduced when treated with AZA. We tested our hypothesis in a three-dimensional in vitro astrocyte model of mTBI. Samples were subject to no stretch (control) or one high-speed stretch (mTBI) injury. AQP4 expression was significantly increased 24 hours after mTBI. mTBI resulted in a significant increase in the cell swelling within 30 min of mTBI, which was significantly reduced in the presence of AZA. Cell death and expression of S100B was significantly reduced when AZA was added shortly before mTBI stretch. Overall, our data point to occurrence of astrocyte swelling immediately following mTBI, and AZA as a promising treatment to mitigate downstream cellular mortality.

The central role of renal microcirculatory dysfunction in the pathogenesis of acute kidney injury.

PubMed

Ince, Can

2014-01-01

Acute kidney injury (AKI) is a rapidly developing condition often associated with critical illness, with a high degree of morbidity and mortality, whose pathophysiology is ill understood. Recent investigations have identified the dysfunction of the renal microcirculation and its cellular and subcellular constituents as being central to the etiology of AKI. Injury is caused by inflammatory activation involving endothelial leucocyte interactions in combination with dysregulation of the homeostatis between oxygen, nitric oxide, and reactive oxygen species. Effective therapies expected to resolve AKI will have to control inflammation and restore this homeostasis. In order to apply and guide these therapies effectively, diagnostic tools aimed at physiological biomarkers of AKI for monitoring renal microcirculatory function in advance of changes in pharmacological biomarkers associated with structural damage of the kidney will need to be developed. 2014 S. Karger AG, Basel.

Risk factors for and the prevention of acute kidney injury after abdominal surgery.

PubMed

An, Yongbo; Shen, Kai; Ye, Yingjiang

2018-06-01

Postoperative acute kidney injury in patients undergoing abdominal surgery is not rare and often results in bad outcomes for patients. The incidence of postoperative acute kidney injury is hard to evaluate reliably due to its non-unified definitions in different studies. Risk factors for acute kidney injury specific to abdominal surgery include preoperative renal insufficiency, intraabdominal hypertension, blood transfusion, bowel preparation, perioperative dehydration, contrast agent and nephrotoxic drug use. Among these, preoperative renal insufficiency is the strongest predictor of acute kidney injury. The peri-operative management of high-risk patients should include meticulous selection of fluid solutions. Balanced crystalloid solutions and albumin are generally thought to be relatively safe, while the safety of hydroxyethyl starch solutions has been controversial. The purpose of the present review is to discuss the current knowledge regarding postoperative acute kidney injury in abdominal surgical settings to help surgeons make better decisions concerning the peri-operative management.

An overview of strength training injuries: acute and chronic.

PubMed

Lavallee, Mark E; Balam, Tucker

2010-01-01

This article introduces the history of strength training, explains the many different styles of strength training, and discusses common injuries specific to each style. Strength training is broken down into five disciplines: basic strength or resistance training, bodybuilding, power lifting, style-dependant strength sports (e.g., strongman competitions, Highland games, field events such as shot put, discus, hammer throw, and javelin), and Olympic-style weightlifting. Each style has its own principal injuries, both acute and chronic, related to the individual technique. Acute injuries should be further categorized as emergent or nonemergent. Specific age-related populations (i.e., the very young and the aging athlete) carry additional considerations.

Maternal organ donation and acute injuries in surviving children.

PubMed

Redelmeier, Donald A; Woodfine, Jason D; Thiruchelvam, Deva; Scales, Damon C

2014-12-01

The purpose of this study is to test whether maternal deceased organ donation is associated with rates of subsequent acute injuries among surviving children after their mother's death. This is a longitudinal cohort analysis of children linked to mothers who died of a catastrophic brain event in Ontario, Canada, between April 1988 and March 2012. Surviving children were distinguished by whether their mother was an organ donor after death. The primary outcome was an acute injury event in surviving children during the year after their mother's death. Surviving children (n=454) had a total of 293 injury events during the year after their mother's death, equivalent to an average of 65 events per 100 children per year and a significant difference comparing children of mothers who were organ donors to children of mothers who were not organ donors (21 vs 82, P<.001). This difference in subsequent injury rates between groups was equal to a 76% relative reduction in risk (95% confidence interval, 62%-85%). Deceased organ donation was associated with a reduction in excess acute injuries among surviving children after their mother's death. An awareness of this positive association provides some reassurance about deceased organ donation programs. Copyright © 2014 Elsevier Inc. All rights reserved.

Differences in the Cellular Response to Acute Spinal Cord Injury between Developing and Mature Rats Highlights the Potential Significance of the Inflammatory Response

PubMed Central

Sutherland, Theresa C.; Mathews, Kathryn J.; Mao, Yilin; Nguyen, Tara; Gorrie, Catherine A.

2017-01-01

There exists a trend for a better functional recovery from spinal cord injury (SCI) in younger patients compared to adults, which is also reported for animal studies; however, the reasons for this are yet to be elucidated. The post injury tissue microenvironment is a complex milieu of cells and signals that interact on multiple levels. Inflammation has been shown to play a significant role in this post injury microenvironment. Endogenous neural progenitor cells (NPC), in the ependymal layer of the central canal, have also been shown to respond and migrate to the lesion site. This study used a mild contusion injury model to compare adult (9 week), juvenile (5 week) and infant (P7) Sprague-Dawley rats at 24 h, 1, 2, and 6 weeks post-injury (n = 108). The innate cells of the inflammatory response were examined using counts of ED1/IBA1 labeled cells. This found a decreased inflammatory response in the infants, compared to the adult and juvenile animals, demonstrated by a decreased neutrophil infiltration and macrophage and microglial activation at all 4 time points. Two other prominent cellular contributors to the post-injury microenvironment, the reactive astrocytes, which eventually form the glial scar, and the NPC were quantitated using GFAP and Nestin immunohistochemistry. After SCI in all 3 ages there was an obvious increase in Nestin staining in the ependymal layer, with long basal processes extending into the parenchyma. This was consistent between age groups early post injury then deviated at 2 weeks. The GFAP results also showed stark differences between the mature and infant animals. These results point to significant differences in the inflammatory response between infants and adults that may contribute to the better recovery indicated by other researchers, as well as differences in the overall injury progression and cellular responses. This may have important consequences if we are able to mirror and manipulate this response in patients of all ages; however

ATP and microfilaments in cellular oxidant injury.

PubMed Central

Hinshaw, D. B.; Armstrong, B. C.; Burger, J. M.; Beals, T. F.; Hyslop, P. A.

1988-01-01

Oxidant injury produces dramatic changes in cytoskeletal organization and cell shape. ATP synthetic pathways are major targets of oxidant injury resulting in rapid depletion of cellular ATP following oxidant exposure. The relation of ATP depletion to the changes in microfilament organization seen following H2O2 exposure were examined in the P388D1 cell line. Three hours of glucose depletion alone resulted in a decline in cellular ATP levels to less than 10% of controls, which was comparable to ATP levels in cells 30 to 60 minutes after exposure to 5 mM H2O2 in the presence of glucose. Adherent cells stained with rhodamine phalloidin, a probe specific for polymerized (F) actin, revealed a progressive shortening of microfilaments into globular aggregates within cells depleted of glucose over 3 hours, a pattern similar to earlier observations of H2O2-injured cells after 1 hour. The changes in cellular ATP associated with glucose depletion or H2O2 exposure were then correlated with G actin content measured by the DNAse 1 inhibition assay. No real differences in G actin content as a percentage of total actin were seen in P388D1 cells following 3 hours of glucose depletion or 30 to 60 minutes after exposure to 5 mM H2O2. But 2 to 3 hours after exposure to H2O2 there was a progressive decrease in G actin as a percentage of total actin within the cells. Transmission electron microscopy of cells depleted of glucose for 3 h or 1 hour after exposure to H2O2 revealed the presence of side-to-side aggregates or bundles of microfilaments within the cells. These observations suggest that declining levels of ATP either from metabolic inhibition or H2O2 injury are correlated with the fragmentation and shortening of microfilaments into aggregates. No net change in monomeric or polymeric actin was necessary for this to occur. However, at later time points after H2O2 exposure some actin assembly did occur. Images p[484]-a p481-a p482-a Figure 2 Figure 3 PMID:3414780

Evolution of Acute Kidney Injury and Its Association With Systemic Hemodynamics in Children With Fluid-Refractory Septic Shock.

PubMed

Deep, Akash; Sagar, Hiremath; Goonasekera, Chulananda; Karthikeyan, Palaniswamy; Brierley, Joe; Douiri, Abdel

2018-07-01

There are no studies in pediatrics evaluating the progression of acute kidney injury in septic shock. We investigated the evolution of sepsis-associated acute kidney injury and its association with systemic hemodynamics in children with fluid-refractory septic shock. Prospective cohort study. PICU of a tertiary care hospital. All patients with fluid-refractory septic shock (n = 61) between September 2010 and February 2014. Hemodynamic variables using noninvasive ultrasound cardiac output monitor were measured at admission and 6 hourly thereafter till 48 hours. We used the Kidney Disease: Improving Global Outcomes criteria to define and stage acute kidney injury. Associations between various hemodynamic variables and development of acute kidney injury were evaluated. Severe acute kidney injury was defined as stage 2 or 3 acute kidney injury and was compared with no acute kidney injury or stage 1 acute kidney injury. Severe acute kidney injury developed in 29.5% (n = 18) of the 61 children with fluid-refractory septic shock, whereas 43 patients (70.49%) had either no or stage 1 acute kidney injury. Most patients who developed acute kidney injury did so within the first 48 hours of PICU admission. Severe acute kidney injury conferred a three-fold increased risk of death by day 28 (hazard ratio, 3.23; 95% CI, 1.52-6.67; p = 0.002), longer ICU stay, and increased duration of mechanical ventilation. Central venous pressure at presentation was higher in severe acute kidney injury by 5 cm H2O. Highest lactate in the first 24 hours of PICU admission, low diastolic blood pressure, low systemic vascular resistance index at admission were associated with severe acute kidney injury. This model reliably predicted stage 2/3 acute kidney injury by day 3 with area under the curve equals to 94%; 95% CI, 88.3-99.99. None of the other hemodynamic variables showed any association with severe acute kidney injury. Manifestations of sepsis-associated acute kidney injury often occur

Activation of cellular immune response in acute pancreatitis.

PubMed Central

Mora, A; Pérez-Mateo, M; Viedma, J A; Carballo, F; Sánchez-Payá, J; Liras, G

1997-01-01

BACKGROUND: Inflammatory mediators have recently been implicated as potential markers of severity in acute pancreatitis. AIMS: To determine the value of neopterin and polymorphonuclear (PMN) elastase as markers of activation of cellular immunity and as early predictors of disease severity. PATIENTS: Fifty two non-consecutive patients classified according to their clinical outcome into mild (n = 26) and severe pancreatitis (n = 26). METHODS: Neopterin in serum and the PMN elastase/A1PI complex in plasma were measured during the first three days of hospital stay. RESULTS: Within three days after the onset of acute pancreatitis, PMN elastase was significantly higher in the severe pancreatitis group. Patients with severe disease also showed significantly higher values of neopterin on days 1 and 2 but not on day 3 compared with patients with mild disease. There was a significant correlation between PMN elastase and neopterin values on days 1 and 2. PMN elastase on day 1 predicted disease severity with a sensitivity of 76.7% and a specificity of 91.6%. Neopterin did not surpass PMN elastase in the probability of predicting disease severity. CONCLUSIONS: These data show that activation of cellular immunity is implicated in the pathogenesis of acute pancreatitis and may be a main contributory factor to disease severity. Neopterin was not superior to PMN elastase in the prediction of severity. PMID:9245935

Acute diabetes insipidus in severe head injury: a prospective study.

PubMed

Hadjizacharia, Pantelis; Beale, Elizabeth O; Inaba, Kenji; Chan, Linda S; Demetriades, Demetrios

2008-10-01

The incidence and risk factors for acute diabetes insipidus after severe head injury and the effect of this complication on outcomes have not been evaluated in any large prospective studies. We conducted a prospective study of all patients admitted to the surgical ICU of a Level I trauma center with severe head injury (head Abbreviated Injury Score [AIS] >or= 3). The following potential risk factors with p < 0.2 on bivariate analysis were included in a stepwise logistic regression to identify independent risk factors for diabetes insipidus and its association with mortality: age, mechanism of injury (blunt or penetrating), blood pressure, Glasgow Coma Scale, Injury Severity Score, head and other body area AIS, skull fracture, cerebral edema and shift, intracranial hemorrhage, and pneumocephaly. There were 436 patients (blunt injuries, 392; penetrating injuries, 44); 387 patients had isolated head injury. Diabetes insipidus occurred in 15.4% of all patients (blunt, 12.5%; penetrating, 40.9%; p < 0.0001) and in 14.7% of patients with isolated head injury (blunt, 11.8%; penetrating, 39.5%; p < 0.0001). The presence of major extracranial injuries did not influence the incidence of diabetes insipidus. Independent risk factors for diabetes insipidus in isolated head injury were Glasgow Coma Scale3. Diabetes insipidus was an independent risk factor for death (adjusted odds ratio, 3.96; 95% CI [1.65, 9.72]; adjusted p value = 0.002). The incidence of acute diabetes insipidus in severe head injury is high, especially in penetrating injuries. Independent risk factors for diabetes insipidus include a Glasgow Coma Scale3. Acute diabetes insipidus was associated with significantly increased mortality.

Acute vitreoretinal trauma and inflammation after traumatic brain injury in mice.

PubMed

Evans, Lucy P; Newell, Elizabeth A; Mahajan, MaryAnn; Tsang, Stephen H; Ferguson, Polly J; Mahoney, Jolonda; Hue, Christopher D; Vogel, Edward W; Morrison, Barclay; Arancio, Ottavio; Nichols, Russell; Bassuk, Alexander G; Mahajan, Vinit B

2018-03-01

Limited attention has been given to ocular injuries associated with traumatic brain injury (TBI). The retina is an extension of the central nervous system and evaluation of ocular damage may offer a less-invasive approach to gauge TBI severity and response to treatment. We aim to characterize acute changes in the mouse eye after exposure to two different models of TBI to assess the utility of eye damage as a surrogate to brain injury. A model of blast TBI (bTBI) using a shock tube was compared to a lateral fluid percussion injury model (LFPI) using fluid pressure applied directly to the brain. Whole eyes were collected from mice 3 days post LFPI and 24 days post bTBI and were evaluated histologically using a hematoxylin and eosin stain. bTBI mice showed evidence of vitreous detachment in the posterior chamber in addition to vitreous hemorrhage with inflammatory cells. Subretinal hemorrhage, photoreceptor degeneration, and decreased cellularity in the retinal ganglion cell layer was also seen in bTBI mice. In contrast, eyes of LFPI mice showed evidence of anterior uveitis and subcapsular cataracts. We demonstrated that variations in the type of TBI can result in drastically different phenotypic changes within the eye. As such, molecular and phenotypic changes in the eye following TBI may provide valuable information regarding the mechanism, severity, and ongoing pathophysiology of brain injury. Because vitreous samples are easily obtained, molecular changes within the eye could be utilized as biomarkers of TBI in human patients.

[Acute kidney injury-emergency or coincidence?].

PubMed

Öttl, Tobias

2013-02-27

An unifying definition of acute kidney injury as a precursor of acute renal failure has been published in march last year. Its remarkable mortality makes an early diagnosis an important goal. New biomarkers will be an important step to reach this goal in the near future. Depending on the underlying cause, therapeutic actions should be realized as soon as possible to diminish in-hospital mortality and chronic nephropathy. Intensive care units often are the first to test for new active substances.

Urinary NGAL in patients with and without acute kidney injury in a cardiology intensive care unit

PubMed Central

Watanabe, Mirian; Silva, Gabriela Fulan e; da Fonseca, Cassiane Dezoti; Vattimo, Maria de Fatima Fernandes

2014-01-01

Objective To assess the diagnostic and prognostic efficacy of urine neutrophil gelatinase-associated lipocalin in patients admitted to an intensive care unit. Methods Longitudinal, prospective cohort study conducted in a cardiology intensive care unit. The participants were divided into groups with and without acute kidney injury and were followed from admission to the intensive care unit until hospital discharge or death. Serum creatinine, urine output and urine neutrophil gelatinase-associated lipocalin were measured 24 and 48 hours after admission. Results A total of 83 patients admitted to the intensive care unit for clinical reasons were assessed, most being male (57.8%). The participants were divided into groups without acute kidney injury (N=18), with acute kidney injury (N=28) and with severe acute kidney injury (N=37). Chronic diseases, mechanical ventilation and renal replacement therapy were more common in the groups with acute kidney injury and severe acute kidney injury, and those groups exhibited longer intensive care unit stay and hospital stay and higher mortality. Serum creatinine did not change significantly in the group with acute kidney injury within the first 24 hours of admission to the intensive care unit, although, urine neutrophil gelatinase-associated lipocalin was high in the groups with acute kidney injury and severe acute kidney injury (p<0.001). Increased urine neutrophil gelatinase-associated lipocalin was associated with death. Conclusion An increase in urine neutrophil gelatinase-associated lipocalin precedes variations in serum creatinine in patients with acute kidney injury and may be associated with death. PMID:25607262

Diabetes, insulin, and development of acute lung injury

PubMed Central

Honiden, Shyoko; Gong, Michelle N.

2009-01-01

Objectives Recently, many studies have investigated the immunomodulatory effects of insulin and glucose control in critical illness. This review examines evidence regarding the relationship between diabetes and the development of acute lung injury/acute respiratory distress syndrome (ALI/ARDS), reviews studies of lung injury related to glycemic and nonglycemic metabolic features of diabetes, and examines the effect of diabetic therapies. Data Sources and Study Selection A MEDLINE/PubMed search from inception to August 1, 2008, was conducted using the search terms acute lung injury, acute respiratory distress syndrome, hyperglycemia, diabetes mellitus, insulin, hydroxymethylglutaryl-CoA reductase inhibitors (statins), angiotensin-converting enzyme inhibitor, and peroxisome proliferator-activated receptors, including combinations of these terms. Bibliographies of retrieved articles were manually reviewed. Data Extraction and Synthesis Available studies were critically reviewed, and data were extracted with special attention to the human and animal studies that explored a) diabetes and ALI; b) hyperglycemia and ALI; c) metabolic nonhyperglycemic features of diabetes and ALI; and d) diabetic therapies and ALI. Conclusions Clinical and experimental data indicate that diabetes is protective against the development of ALI/ARDS. The pathways involved are complex and likely include effects of hyperglycemia on the inflammatory response, metabolic abnormalities in diabetes, and the interactions of therapeutic agents given to diabetic patients. Multidisciplinary, multifaceted studies, involving both animal models and clinical and molecular epidemiology techniques, are essential. PMID:19531947

Acute injuries in recreational and competitive surfers: incidence, severity, location, type, and mechanism.

PubMed

Furness, James; Hing, Wayne; Walsh, Joe; Abbott, Allan; Sheppard, Jeremy M; Climstein, Mike

2015-05-01

There are an estimated 37 million surfers worldwide, with 2.5 million recreational surfers in Australia. The recreational activity and sport of surfing has grown dramatically since the 1960s, but scientific research has been poorly mirrored in comparison with most other mainstream sports. To identify the incidence, severity, location, type, and mechanism of acute injuries in recreational and competitive surfers over a 12-month period. Descriptive epidemiology study. An online survey using an open-source survey application was utilized. The survey consisted of 2 primary sections: Section 1 included demographic information and participation levels (age, height, weight, hours surfed, competitive level); section 2 incorporated injury type, mechanism, severity, and injury management. A total of 1348 participants (91.3% males; 43.1% competitive surfers) were included in data analysis. A total of 512 acute injuries were classified as major, providing an incidence proportion of 0.38 (CI, 0.35-0.41) acute injuries per year. The incidence rate was calculated to be 1.79 (CI, 1.67-1.92) major injuries per 1000 hours of surfing. The shoulder, ankle, and head/face regions had the highest frequencies of acute injury, representing 16.4%, 14.6%, and 13.3%, respectively. Injuries were predominantly of muscular, joint, and skin origin, representing 30.3%, 27.7%, and 18.9%, respectively. Skin injuries were primarily a result of direct trauma, while joint and muscular injuries were mainly a result of maneuvers performed and repetitive actions. Key risk factors that increased the incidence of sustaining an acute injury included competitive status, hours surfed (>6.5 hours/week), and the ability to perform aerial maneuvers. The incidence proportion for surfers completing aerial maneuvers was calculated to be 0.48 (CI, 0.39-0.58) major injuries per year, this being the highest incidence proportion irrespective of competitive status. This is the largest surfing-specific survey that

Acute Kidney Injury and Subsequent Frailty Status in Survivors of Critical Illness: A Secondary Analysis.

PubMed

Abdel-Kader, Khaled; Girard, Timothy D; Brummel, Nathan E; Saunders, Christina T; Blume, Jeffrey D; Clark, Amanda J; Vincz, Andrew J; Ely, E Wesley; Jackson, James C; Bell, Susan P; Archer, Kristin R; Ikizler, T Alp; Pandharipande, Pratik P; Siew, Edward D

2018-05-01

Acute kidney injury frequently complicates critical illness and is associated with high morbidity and mortality. Frailty is common in critical illness survivors, but little is known about the impact of acute kidney injury. We examined the association of acute kidney injury and frailty within a year of hospital discharge in survivors of critical illness. Secondary analysis of a prospective cohort study. Medical/surgical ICU of a U.S. tertiary care medical center. Three hundred seventeen participants with respiratory failure and/or shock. None. Acute kidney injury was determined using Kidney Disease Improving Global Outcomes stages. Clinical frailty status was determined using the Clinical Frailty Scale at 3 and 12 months following discharge. Covariates included mean ICU Sequential Organ Failure Assessment score and Acute Physiology and Chronic Health Evaluation II score as well as baseline comorbidity (i.e., Charlson Comorbidity Index), kidney function, and Clinical Frailty Scale score. Of 317 patients, 243 (77%) had acute kidney injury and one in four patients with acute kidney injury was frail at baseline. In adjusted models, acute kidney injury stages 1, 2, and 3 were associated with higher frailty scores at 3 months (odds ratio, 1.92; 95% CI, 1.14-3.24; odds ratio, 2.40; 95% CI, 1.31-4.42; and odds ratio, 4.41; 95% CI, 2.20-8.82, respectively). At 12 months, a similar association of acute kidney injury stages 1, 2, and 3 and higher Clinical Frailty Scale score was noted (odds ratio, 1.87; 95% CI, 1.11-3.14; odds ratio, 1.81; 95% CI, 0.94-3.48; and odds ratio, 2.76; 95% CI, 1.34-5.66, respectively). In supplemental and sensitivity analyses, analogous patterns of association were observed. Acute kidney injury in survivors of critical illness predicted worse frailty status 3 and 12 months postdischarge. These findings have important implications on clinical decision making among acute kidney injury survivors and underscore the need to understand the drivers of

Transcranial amelioration of inflammation and cell death after brain injury

NASA Astrophysics Data System (ADS)

Roth, Theodore L.; Nayak, Debasis; Atanasijevic, Tatjana; Koretsky, Alan P.; Latour, Lawrence L.; McGavern, Dorian B.

2014-01-01

Traumatic brain injury (TBI) is increasingly appreciated to be highly prevalent and deleterious to neurological function. At present, no effective treatment options are available, and little is known about the complex cellular response to TBI during its acute phase. To gain insights into TBI pathogenesis, we developed a novel murine closed-skull brain injury model that mirrors some pathological features associated with mild TBI in humans and used long-term intravital microscopy to study the dynamics of the injury response from its inception. Here we demonstrate that acute brain injury induces vascular damage, meningeal cell death, and the generation of reactive oxygen species (ROS) that ultimately breach the glial limitans and promote spread of the injury into the parenchyma. In response, the brain elicits a neuroprotective, purinergic-receptor-dependent inflammatory response characterized by meningeal neutrophil swarming and microglial reconstitution of the damaged glial limitans. We also show that the skull bone is permeable to small-molecular-weight compounds, and use this delivery route to modulate inflammation and therapeutically ameliorate brain injury through transcranial administration of the ROS scavenger, glutathione. Our results shed light on the acute cellular response to TBI and provide a means to locally deliver therapeutic compounds to the site of injury.

Transcutaneous electrical neurostimulation in musculoskeletal pain of acute spinal cord injuries.

PubMed

Richardson, R R; Meyer, P R; Cerullo, L J

1980-01-01

Cervical, thoracic, thoracolumbar, and lumbar fractures associated with physiologic complete or incomplete spinal cord injuries frequently have severe soft-tissue injury as well as severe pain associated with the site or area of injury. Transcutaneous electrical neurostimulation has proved effective in the treatment of various causes of severe acute and chronic intractable pains. We applied this modality to a group of 20 patients who had acute spinal cord injuries and pain associated with severe, extensive soft-tissue injury. Its advantages include ease of application, lack of major complications, increased intestinal peristalsis, and avoidance of narcotic analgesic medications. It also produced significant (greater than 50%) pain relief in 75% of patients treated by transcutaneous electrical neurostimulation.

[Strategies for prevention of acute kidney injury in cardiac surgery: an integrative review].

PubMed

Santana-Santos, Eduesley; Marcusso, Marila Eduara Fátima; Rodrigues, Amanda Oliveira; Queiroz, Fernanda Gomes de; Oliveira, Larissa Bertacchini de; Rodrigues, Adriano Rogério Baldacin; Palomo, Jurema da Silva Herbas

2014-01-01

Acute kidney injury is a common complication after cardiac surgery and is associated with increased morbidity and mortality and increased length of stay in the intensive care unit. Considering the high prevalence of acute kidney injury and its association with worsened prognosis, the development of strategies for renal protection in hospitals is essential to reduce the associated high morbidity and mortality, especially for patients at high risk of developing acute kidney injury, such as patients who undergo cardiac surgery. This integrative review sought to assess the evidence available in the literature regarding the most effective interventions for the prevention of acute kidney injury in patients undergoing cardiac surgery. To select the articles, we used the CINAHL and MedLine databases. The sample of this review consisted of 16 articles. After analyzing the articles included in the review, the results of the studies showed that only hydration with saline has noteworthy results in the prevention of acute kidney injury. The other strategies are controversial and require further research to prove their effectiveness.

Integrating microRNAs into a system biology approach to acute lung injury.

PubMed

Zhou, Tong; Garcia, Joe G N; Zhang, Wei

2011-04-01

Acute lung injury (ALI), including the ventilator-induced lung injury (VILI) and the more severe acute respiratory distress syndrome (ARDS), are common and complex inflammatory lung diseases potentially affected by various genetic and nongenetic factors. Using the candidate gene approach, genetic variants associated with immune response and inflammatory pathways have been identified and implicated in ALI. Because gene expression is an intermediate phenotype that resides between the DNA sequence variation and the higher level cellular or whole-body phenotypes, the illustration of gene expression regulatory networks potentially could enhance understanding of disease susceptibility and the development of inflammatory lung syndromes. MicroRNAs (miRNAs) have emerged as a novel class of gene regulators that play critical roles in complex diseases including ALI. Comparisons of global miRNA profiles in animal models of ALI and VILI identified several miRNAs (eg, miR-146a and miR-155) previously implicated in immune response and inflammatory pathways. Therefore, via regulation of target genes in these biological processes and pathways, miRNAs potentially contribute to the development of ALI. Although this line of inquiry exists at a nascent stage, miRNAs have the potential to be critical components of a comprehensive model for inflammatory lung disease built by a systems biology approach that integrates genetic, genomic, proteomic, epigenetic as well as environmental stimuli information. Given their particularly recognized role in regulation of immune and inflammatory responses, miRNAs also serve as novel therapeutic targets and biomarkers for ALI/ARDS or VILI, thus facilitating the realization of personalized medicine for individuals with acute inflammatory lung disease. Copyright © 2011 Mosby, Inc. All rights reserved.

Acute Kidney Injury as a Risk Factor for Delirium and Coma during Critical Illness.

PubMed

Siew, Edward D; Fissell, William H; Tripp, Christina M; Blume, Jeffrey D; Wilson, Matthew D; Clark, Amanda J; Vincz, Andrew J; Ely, E Wesley; Pandharipande, Pratik P; Girard, Timothy D

2017-06-15

Acute kidney injury may contribute to distant organ dysfunction. Few studies have examined kidney injury as a risk factor for delirium and coma. To examine whether acute kidney injury is associated with delirium and coma in critically ill adults. In a prospective cohort study of intensive care unit patients with respiratory failure and/or shock, we examined the association between acute kidney injury and daily mental status using multinomial transition models adjusting for demographics, nonrenal organ failure, sepsis, prior mental status, and sedative exposure. Acute kidney injury was characterized daily using the difference between baseline and peak serum creatinine and staged according to Kidney Disease Improving Global Outcomes criteria. Mental status (normal vs. delirium vs. coma) was assessed daily with the Confusion Assessment Method for the ICU and Richmond Agitation-Sedation Scale. Among 466 patients, stage 2 acute kidney injury was a risk factor for delirium (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.07-2.26) and coma (OR, 2.04; 95% CI, 1.25-3.34) as was stage 3 injury (OR for delirium, 2.56; 95% CI, 1.57-4.16) (OR for coma, 3.34; 95% CI, 1.85-6.03). Daily peak serum creatinine (adjusted for baseline) values were also associated with delirium (OR, 1.35; 95% CI, 1.18-1.55) and coma (OR, 1.44; 95% CI, 1.20-1.74). Renal replacement therapy modified the association between stage 3 acute kidney injury and daily peak serum creatinine and both delirium and coma. Acute kidney injury is a risk factor for delirium and coma during critical illness.

Delayed Consequences of Acute Kidney Injury

PubMed Central

Parr, Sharidan K; Siew, Edward D

2016-01-01

Acute kidney injury (AKI) is an increasingly common complication of hospitalization and acute illness. Experimental data indicate that AKI may cause permanent kidney damage through tubulointerstitial fibrosis and progressive nephron loss, while also lowering the threshold for subsequent injury. Furthermore, preclinical data suggest that AKI may also cause distant organ dysfunction. The extension of these findings to human studies suggests long-term consequences of AKI including, but not limited to recurrent AKI, progressive kidney disease, elevated blood pressure, cardiovascular events, and mortality. As the number of AKI survivors increases, the need to better understand the mechanisms driving these processes becomes paramount. Optimizing care for AKI survivors will require understanding the short- and long-term risks associated with AKI, identifying patients at highest risk for poor outcomes, and testing interventions that target modifiable risk factors. In this review, we examine the literature describing the association between AKI and long-term outcomes and highlight opportunities for further research and potential intervention. PMID:27113695

Influence of Acute Kidney Injury Defined by the Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease Score on the Clinical Course of PICU Patients.

PubMed

Cabral, Felipe Cezar; Ramos Garcia, Pedro Celiny; Mattiello, Rita; Dresser, Daiane; Fiori, Humberto Holmer; Korb, Cecilia; Dalcin, Tiago Chagas; Piva, Jefferson Pedro

2015-10-01

To evaluate the predictive value of the pediatric-modified Risk, Injury, Failure, Loss, End-stage renal disease criteria for disease course severity in patients with or without acute kidney injury admitted to a PICU. Retrospective cohort study. A 12-bed PICU at a tertiary referral center in Southern Brazil. All patients admitted to the study unit over a 1-year period. A database of all eligible patients was analyzed retrospectively. Patients were classified by pediatric-modified Risk, Injury, Failure, Loss, End-stage renal disease score at admission and worst pediatric-modified Risk, Injury, Failure, Loss, End-stage renal disease score during PICU hospitalization. The outcomes of interest were length of PICU stay, duration of mechanical ventilation, duration of vasoactive drug therapy, and mortality. The Pediatric Index of Mortality 2 was used to assess overall disease severity at the time of PICU admission. Of 375 patients, 169 (45%) presented acute kidney injury at the time of admission and 37 developed acute kidney injury during PICU stay, for a total of 206 of 375 patients (55%) diagnosed with acute kidney injury during the study period. The median Pediatric Index of Mortality 2 score predicted a mortality rate of 9% among non-acute kidney injury patients versus a mortality rate of 16% among acute kidney injury patients (p = 0.006). The mortality of patients classified as pediatric-modified Risk, Injury, Failure, Loss, End-stage renal disease F was double that predicted by Pediatric Index of Mortality 2 (7 vs 3.2). Patients classified as having severe acute kidney injury (pediatric-modified Risk, Injury, Failure, Loss, End-stage renal disease I + F) exhibited higher mortality (14.1%; p = 0.001) and prolonged PICU length of stay (median, 7 d; p = 0.001) when compared with other patients. Acute kidney injury is a very frequent occurrence among patients admitted to PICUs. The degree of acute kidney injury severity, as assessed by the pediatric-modified Risk

Acute kidney injury in acute liver failure: a review.

PubMed

Moore, Joanna K; Love, Eleanor; Craig, Darren G; Hayes, Peter C; Simpson, Kenneth J

2013-11-01

Acute liver failure is a rare and often devastating condition consequent on massive liver cell necrosis that frequently affects young, previously healthy individuals resulting in altered cognitive function, coagulopathy and peripheral vasodilation. These patients frequently develop concurrent acute kidney injury (AKI). This abrupt and sustained decline in renal function, through a number of pathogenic mechanisms such as renal hypoperfusion, direct drug-induced nephrotoxicity or sepsis/systemic inflammatory response contributes to increased morbidity and is strongly associated with a worse prognosis. Improved understanding of the pathophysiology AKI in the context of acute liver failure may be beneficial in a number of areas; the development of new and sensitive biomarkers of renal dysfunction, refining prognosis and organ allocation, and ultimately leading to the development of novel treatment strategies, these issues are discussed in more detail in this expert review.

Systems biomarkers as acute diagnostics and chronic monitoring tools for traumatic brain injury

NASA Astrophysics Data System (ADS)

Wang, Kevin K. W.; Moghieb, Ahmed; Yang, Zhihui; Zhang, Zhiqun

2013-05-01

Traumatic brain injury (TBI) is a significant biomedical problem among military personnel and civilians. There exists an urgent need to develop and refine biological measures of acute brain injury and chronic recovery after brain injury. Such measures "biomarkers" can assist clinicians in helping to define and refine the recovery process and developing treatment paradigms for the acutely injured to reduce secondary injury processes. Recent biomarker studies in the acute phase of TBI have highlighted the importance and feasibilities of identifying clinically useful biomarkers. However, much less is known about the subacute and chronic phases of TBI. We propose here that for a complex biological problem such as TBI, multiple biomarker types might be needed to harness the wide range of pathological and systemic perturbations following injuries, including acute neuronal death, neuroinflammation, neurodegeneration and neuroregeneration to systemic responses. In terms of biomarker types, they range from brain-specific proteins, microRNA, genetic polymorphism, inflammatory cytokines and autoimmune markers and neuro-endocrine hormones. Furthermore, systems biology-driven biomarkers integration can help present a holistic approach to understanding scenarios and complexity pathways involved in brain injury.

Acute closed radial nerve injury

PubMed Central

Tuncel, Umut; Turan, Aydin; Kostakoglu, Naci

2011-01-01

We present a 45-year-old patient who had acute radial nerve palsy following a blunt trauma without any fracture or dislocation. He was injured by strucking in a combat three months ago. The patient has been followed by application of a long-arm plaster cast before referred to our clinic. Preoperative electromyoneurography and magnetic resonance imaging (MRI) indicated that there was a radial nerve injury on humeral groove. The British Medical Research Council (MRC) grade was 2/5 on his wrist preoperatively. The patient underwent an operation under general anesthesia. It was seen to be a second-degree nerve injury. The patient has subsequently regained full movement on his wrist and finger extension in six months. We suggest that a detailed clinical and electrodiagnostical evaluation is necessary in patients who have radial nerve injury when deciding the treatment, conservative or surgical. PMID:22347334

Potential Application of Viral Empty Capsids for the Treatment of Acute Lung Injury/Acute Respiratory Distress Syndrome

DTIC Science & Technology

2016-07-01

Particles (VLPs). The rationale is based on the beneficial effect of SV40 VLPs on an Acute Kidney Injury (AKI) model in mice, previously demonstrated...signaling which, as was demonstrated, protect mice kidneys from apoptosis, necrosis and consequent damage induced by a toxic (mercury) insult, increasing...recombinant VP1, without any genetic material. Using a mouse model for toxic Acute Kidney Injury (AKI), we demonstrated that systemic

Diagnostic Tools for Acute Anterior Cruciate Ligament Injury: GNRB, Lachman Test, and Telos.

PubMed

Ryu, Seung Min; Na, Ho Dong; Shon, Oog Jin

2018-06-01

The purpose of this study is to compare the accuracy of the GNRB arthrometer (Genourob), Lachman test, and Telos device (GmbH) in acute anterior cruciate ligament (ACL) injuries and to evaluate the accuracy of each diagnostic tool according to the length of time from injury to examination. From September 2015 to September 2016, 40 cases of complete ACL rupture were reviewed. We divided the time from injury to examination into three periods of 10 days each and analyzed the diagnostic tools according to the time frame. An analysis of the area under the curve (AUC) of a receiver operating characteristic curve showed that all diagnostic tools were fairly informative. The GNRB showed a higher AUC than other diagnostic tools. In 10 cases assessed within 10 days after injury, the GNRB showed statistically significant side-to-side difference in laxity (p＜0.001), whereas the Telos test and Lachman test did not show significantly different laxity (p=0.541 and p=0.413, respectively). All diagnostic values of the GNRB were better than other diagnostic tools in acute ACL injuries. The GNRB was more effective in acute ACL injuries examined within 10 days of injury. The GNRB arthrometer can be a useful diagnostic tool for acute ACL injuries.

Targeting Transfusion-Related Acute Lung Injury: The Journey From Basic Science to Novel Therapies.

PubMed

Semple, John W; McVey, Mark J; Kim, Michael; Rebetz, Johan; Kuebler, Wolfgang M; Kapur, Rick

2018-05-01

Transfusion-related acute lung injury is characterized by the onset of respiratory distress and acute lung injury following blood transfusion, but its pathogenesis remains poorly understood. Generally, a two-hit model is presumed to underlie transfusion-related acute lung injury with the first hit being risk factors present in the transfused patient (such as inflammation), whereas the second hit is conveyed by factors in the transfused donor blood (such as antileukocyte antibodies). At least 80% of transfusion-related acute lung injury cases are related to the presence of donor antibodies such as antihuman leukocyte or antihuman neutrophil antibodies. The remaining cases may be related to nonantibody-mediated factors such as biolipids or components related to storage and ageing of the transfused blood cells. At present, transfusion-related acute lung injury is the leading cause of transfusion-related fatalities and no specific therapy is clinically available. In this article, we critically appraise and discuss recent preclinical (bench) insights related to transfusion-related acute lung injury pathogenesis and their therapeutic potential for future use at the patients' bedside in order to combat this devastating and possibly fatal complication of transfusion. We searched the PubMed database (until August 22, 2017). Using terms: "Transfusion-related acute lung injury," "TRALI," "TRALI and therapy," "TRALI pathogenesis." English-written articles focusing on transfusion-related acute lung injury pathogenesis, with potential therapeutic implications, were extracted. We have identified potential therapeutic approaches based on the literature. We propose that the most promising therapeutic strategies to explore are interleukin-10 therapy, down-modulating C-reactive protein levels, targeting reactive oxygen species, or blocking the interleukin-8 receptors; all focused on the transfused recipient. In the long-run, it may perhaps also be advantageous to explore other

Role of Interleukin-10 in Acute Brain Injuries

PubMed Central

Garcia, Joshua M.; Stillings, Stephanie A.; Leclerc, Jenna L.; Phillips, Harrison; Edwards, Nancy J.; Robicsek, Steven A.; Hoh, Brian L.; Blackburn, Spiros; Doré, Sylvain

2017-01-01

Interleukin-10 (IL-10) is an important anti-inflammatory cytokine expressed in response to brain injury, where it facilitates the resolution of inflammatory cascades, which if prolonged causes secondary brain damage. Here, we comprehensively review the current knowledge regarding the role of IL-10 in modulating outcomes following acute brain injury, including traumatic brain injury (TBI) and the various stroke subtypes. The vascular endothelium is closely tied to the pathophysiology of these neurological disorders and research has demonstrated clear vascular endothelial protective properties for IL-10. In vitro and in vivo models of ischemic stroke have convincingly directly and indirectly shown IL-10-mediated neuroprotection; although clinically, the role of IL-10 in predicting risk and outcomes is less clear. Comparatively, conclusive studies investigating the contribution of IL-10 in subarachnoid hemorrhage are lacking. Weak indirect evidence supporting the protective role of IL-10 in preclinical models of intracerebral hemorrhage exists; however, in the limited number of clinical studies, higher IL-10 levels seen post-ictus have been associated with worse outcomes. Similarly, preclinical TBI models have suggested a neuroprotective role for IL-10; although, controversy exists among the several clinical studies. In summary, while IL-10 is consistently elevated following acute brain injury, the effect of IL-10 appears to be pathology dependent, and preclinical and clinical studies often paradoxically yield opposite results. The pronounced and potent effects of IL-10 in the resolution of inflammation and inconsistency in the literature regarding the contribution of IL-10 in the setting of acute brain injury warrant further rigorously controlled and targeted investigation. PMID:28659854

Targeting Extracellular Histones with Novel RNA Biodrugs for the Treatment of Acute Lung Injury

DTIC Science & Technology

2017-10-01

inactivate) circulating histones and prevent the morbidity and mortality associated with multiple organ dysfunction/ acute respiratory distress syndrome ...patients. 15. SUBJECT TERMS Acute lung injury (ALI), acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome , extracellular...are acute lung injury (ALI) from smoke/chlorine gas inhalation, burns, radiation , influenza and severe infection. Only recently have investigators

Preventive mechanisms of agmatine against ischemic acute kidney injury in rats.

PubMed

Sugiura, Takahiro; Kobuchi, Shuhei; Tsutsui, Hidenobu; Takaoka, Masanori; Fujii, Toshihide; Hayashi, Kentaro; Matsumura, Yasuo

2009-01-28

The excitation of renal sympathetic nervous system plays an important role in the development of ischemic acute kidney injury in rats. Recently, we found that agmatine, an adrenaline alpha(2)/imidazoline I(1)-receptor agonist, has preventive effects on ischemic acute kidney injury by suppressing the enhanced renal sympathetic nerve activity during renal ischemia and by decreasing the renal venous norepinephrine overflow after reperfusion. In the present study, we investigated preventive mechanisms of agmatine against ischemic acute kidney injury in rats. Ischemic acute kidney injury was induced by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after the contralateral nephrectomy. Pretreatment with efaroxan (30 mumol/kg, i.v.), an alpha(2)/I(1)-receptor antagonist, abolished the suppressive effects of agmatine on the enhanced renal sympathetic nerve activity during renal ischemia and on the elevated norepinephrine overflow after reperfusion, and eliminated the preventing effects of agmatine on the ischemia/reperfusion-induced renal dysfunction and histological damage. On the other hand, pretreatment with yohimbine (6 mumol/kg, i.v.), an alpha(2)-receptor antagonist, eliminated the preventing effects of agmatine on the ischemia/reperfusion-induced renal injury and norepinephrine overflow, without affecting the lowering effect of agmatine on renal sympathetic nerve activity. These results indicate that agmatine prevents the ischemic renal injury by sympathoinhibitory effect probably via I(1) receptors in central nervous system and by suppressing the norepinephrine overflow through alpha(2) or I(1) receptors on sympathetic nerve endings.

Mechanisms of decreased intestinal epithelial proliferation and increased apoptosis in murine acute lung injury.

PubMed

Husain, Kareem D; Stromberg, Paul E; Woolsey, Cheryl A; Turnbull, Isaiah R; Dunne, W Michael; Javadi, Pardis; Buchman, Timothy G; Karl, Irene E; Hotchkiss, Richard S; Coopersmith, Craig M

2005-10-01

The aim of this study was to determine the effects of acute lung injury on the gut epithelium and examine mechanisms underlying changes in crypt proliferation and apoptosis. The relationship between severity and timing of lung injury to intestinal pathology was also examined. Randomized, controlled study. University research laboratory. Genetically inbred mice. Following induction of acute lung injury, gut epithelial proliferation and apoptosis were assessed in a) C3H/HeN wild-type and C3H/HeJ mice, which lack functional Toll-like receptor 4 (n = 17); b) C57Bl/6 mice that received monoclonal anti-tumor necrosis factor-alpha or control antibody (n = 22); and c) C57Bl/6 wild-type and transgenic mice that overexpress Bcl-2 in their gut epithelium (n = 21). Intestinal epithelial proliferation and death were also examined in animals with differing degrees of lung inflammation (n = 24) as well as in a time course analysis following a fixed injury (n = 18). Acute lung injury caused decreased proliferation and increased apoptosis in crypt epithelial cells in all animals studied. C3H/HeJ mice had higher levels of proliferation than C3H/HeN animals without additional changes in apoptosis. Anti-tumor necrosis factor-alpha antibody had no effect on gut epithelial proliferation or death. Overexpression of Bcl-2 did not change proliferation despite decreasing gut apoptosis. Proliferation and apoptosis were not correlated to severity of lung injury, as gut alterations were lost in mice with more severe acute lung injury. Changes in both gut epithelial proliferation and death were apparent within 12 hrs, but proliferation was decreased 36 hrs following acute lung injury while apoptosis returned to normal. Acute lung injury causes disparate effects on crypt proliferation and apoptosis, which occur, at least in part, through differing mechanisms involving Toll-like receptor 4 and Bcl-2. Severity of lung injury does not correlate with perturbations in proliferation or death in the

Acute stress promotes post-injury brain regeneration in fish.

PubMed

Sinyakov, Michael S; Haimovich, Amihai; Avtalion, Ramy R

2017-12-01

The central nervous system and the immune system, the two major players in homeostasis, operate in the ongoing bidirectional interaction. Stress is the third player that exerts strong effect on these two 'supersystems'; yet, its impact is studied much less. In this work employing carp model, we studied the influence of preliminary stress on neural and immune networks involved in post-injury brain regeneration. The relevant in vivo models of air-exposure stress and precisely directed cerebellum injury have been developed. Neuronal regeneration was evaluated by using specific tracers of cell proliferation and differentiation. Involvement of immune networks was accessed by monitoring the expression of selected T cells markers. Contrast difference between acute and chronic stress manifested in the fact that chronically stressed fish did not survive the brain injury. Neuronal regeneration appeared as a biphasic process whereas involvement of immune system proceeded as a monophasic route. In stressed fish, immune response was fast and accompanied or even preceded neuronal regeneration. In unstressed subjects, immune response took place on the second phase of neuronal regeneration. These findings imply an intrinsic regulatory impact of acute stress on neuronal and immune factors involved in post-injury brain regeneration. Stress activates both neuronal and immune defense mechanisms and thus contributes to faster regeneration. In this context, paradoxically, acute preliminary stress might be considered a distinct asset in speeding up the following post-injury brain regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

Legionnaires disease presenting as acute kidney injury in the absence of pneumonia.

PubMed

Yogarajah, Meera; Sivasambu, Bhradeev

2015-02-17

Legionnaires disease is a pneumonic illness with multisystem involvement. In 1987, Haines et al reported the only reported case of isolated renal disease of legionellosis without concurrent respiratory disease. A 62-year-old man presented with generalised weakness and malaise and watery diarrhoea, and was found to have acute kidney injury on admission. He was initially managed as acute gastroenteritis complicated with dehydration and acute kidney injury with intravenous hydration. Despite adequate hydration, his renal function was worsening day by day. Later in the course of his sickness he developed pneumonic illness and was diagnosed with Legionnaires disease after a positive urine antigen test. We are reporting the second case of Legionnaires disease presenting as an isolated acute kidney injury in the absence of respiratory symptoms on presentation. 2015 BMJ Publishing Group Ltd.

Histopathology of Septic Acute Kidney Injury: A Systematic Review of Experimental Data.

PubMed

Kosaka, Junko; Lankadeva, Yugeesh R; May, Clive N; Bellomo, Rinaldo

2016-09-01

The histopathologic changes associated with septic acute kidney injury are poorly understood, in part, because of the lack of biopsy data in humans. Animal models of septic acute kidney injury may help define such changes. Therefore, we performed a systematic review of the histopathologic changes found in modern experimental septic acute kidney injury models. MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, and PubMed (from January 2007 to February 2015). We reviewed experimental studies reporting findings on the histopathology of contemporary experimental septic acute kidney injury. We focused on the presence or the absence of acute tubular necrosis, tubular cell apoptosis, and other nonspecific findings. We identified 102 studies in 1,059 animals. Among the 1,059 animals, 53 (5.0%) did not have any renal histopathologic changes, but acute tubular necrosis was found in 184 (17.4%). The prevalence of acute tubular necrosis was not related to animal size or model of sepsis and was only found in models with low cardiac output and decreased renal blood flow (p < 0.0001). Only 21 studies (170 animals) assessed the prevalence of tubular cell apoptosis, which was reported in 158 animals (92.9%). The prevalence of tubular cell apoptosis was significantly higher in studies using small animals (p < 0.0001) and in peritonitis models (p < 0.0001). Simultaneous acute tubular necrosis and tubular cell apoptosis was rare (55 animals [32.4%]) and only seen with decreased cardiac output and renal blood flow. Nonspecific changes (vacuolization of tubular cells, loss of brush border, and tubular cell swelling) were each observed in 423 (39.9%), 250 (23.6%) and 243 (22.9%) animals, respectively. In models of experimental septic acute kidney injury in contemporary articles, acute tubular necrosis was relatively uncommon and, when present, reflected the presence of an associated low cardiac output or low renal blood flow syndrome. Tubular cell apoptosis seemed

A return-to-sport algorithm for acute hamstring injuries.

PubMed

Mendiguchia, Jurdan; Brughelli, Matt

2011-02-01

Acute hamstring injuries are the most prevalent muscle injuries reported in sport. Despite a thorough and concentrated effort to prevent and rehabilitate hamstring injuries, injury occurrence and re-injury rates have not improved over the past 28 years. This failure is most likely due to the following: 1) an over-reliance on treating the symptoms of injury, such as subjective measures of "pain", with drugs and interventions; 2) the risk factors investigated for hamstring injuries have not been related to the actual movements that cause hamstring injuries i.e. not functional; and, 3) a multi-factorial approach to assessment and treatment has not been utilized. The purpose of this clinical commentary is to introduce a model for progression through a return-to-sport rehabilitation following an acute hamstring injury. This model is developed from objective and quantifiable tests (i.e. clinical and functional tests) that are structured into a step-by-step algorithm. In addition, each step in the algorithm includes a treatment protocol. These protocols are meant to help the athlete to improve through each phase safely so that they can achieve the desired goals and progress through the algorithm and back to their chosen sport. We hope that this algorithm can serve as a foundation for future evidence based research and aid in the development of new objective and quantifiable testing methods. Copyright © 2010 Elsevier Ltd. All rights reserved.

Acute torn meniscus combined with acute cruciate ligament injury. Second look arthroscopy after 3-month conservative treatment.

PubMed

Ihara, H; Miwa, M; Takayanagi, K; Nakayama, A

1994-10-01

The purpose of this study was to evaluate arthroscopically the natural healing of an acute torn meniscus combined with an acute cruciate ligament injury treated nonoperatively. There were 30 lateral and 10 medial meniscus tears associated with 25 acute anterior cruciate ligament and 7 posterior cruciate ligament injuries in 32 patients. There was more than 1 tear on some menisci for a total of 51 tear sites. Injuries to the menisci and ligaments were allowed to heal without surgery, but were given protective mobilization immediately in order to stimulate stress oriented healing of injured collagen fibers and promote circulation of synovial fluid to the meniscus and ligament. A Kyuro knee brace with a coil spring traction system was used to add adequate but not excessive stress to the associated injured cruciate ligament. All knees were examined and arthroscoped before and after a 3-month treatment period. Results indicated that 69% of the lateral menisci healed completely and 18% healed partially, whereas 58% of the medial menisci healed completely and none healed partially. Twenty of 25 anterior cruciate ligaments and 3 of 7 posterior cruciate ligaments healed satisfactorily. This study indicated that acute tears of the meniscus, even when they occur in association with a cruciate ligament injury, can heal morphologically with nonsurgical treatment.

Formula Feeding Is Independently Associated With Acute Kidney Injury in Very Low Birth Weight Infants.

PubMed

Ginovart, Gemma; Gich, Ignasi; Verd, Sergio

2016-11-01

Successful strategies to prevent neonatal acute kidney injury are lacking. Nevertheless, it is well known that in breastfed babies the excretory needs of the kidney are low because the intake of most nutrients is just above the nutritional requirement. This study aimed to determine whether feeding type predicts acute kidney injury in the very low birth weight infant. One hundred and eighty-six infants were enrolled in this pre-post cohort study (114 infants were included in the only human milk-fed group and 72 in the formula-fed group). Routine biological markers of acute kidney injury were collected in both groups from birth to discharge. Compared with formula feeding, human milk feeding was associated with almost 80% lower odds of acute kidney injury (odds ratio [OR] = 0.2; 95% confidence interval [CI], 0.05-0.77). After confounding variables had been controlled for, formula feeding was independently associated with acute kidney injury in very low birth weight infants. The study showed that, at our institution, acute kidney injury in the neonatal period is frequently associated with the avoidable procedure of formula feeding. Further prospective multicenter studies are needed to determine the generality of this association.

Acute injury of anterior cruciate ligament during karate training.

PubMed

Huang, Kuo-Chin; Hsu, Wei-Hsiu; Wang, Ting-Chung

2007-06-01

A 38-year-old black-belt karate practitioner presented with acute disabling injury of his knee after swift-withdrawal of a reverse-roundhouse-kick. Examination confirmed the diagnosis of grade III ACL tear. Although there are reports documenting injury rate in modern karate, no previous cases of karate-related ACL injuries have been reported. The trauma mechanism is different than ACL injuries during other non-contact and contact sports. The current case report indicates that ACL injury can occur without any contact of the lower limb as a result of dynamic muscular forces during karate training.

Acute Kidney Injury in Patients Undergoing the Extracardiac Fontan Operation With and Without the Use of Cardiopulmonary Bypass.

PubMed

Algaze, Claudia A; Koth, Andrew M; Faberowski, Lisa W; Hanley, Frank L; Krawczeski, Catherine D; Axelrod, David M

2017-01-01

To describe the prevalence and risk factors for acute kidney injury in patients undergoing the extracardiac Fontan operation with and without cardiopulmonary bypass, and to determine whether acute kidney injury is associated with duration of mechanical ventilation, cardiovascular ICU and hospital postoperative length of stay, and early mortality. Single-center retrospective cohort study. Pediatric cardiovascular ICU, university-affiliated children's hospital. Patients with a preoperative creatinine before undergoing first-time extracardiac Fontan between January 1, 2004, and April 30, 2012. None. Acute kidney injury occurred in 55 of 138 patients (39.9%), including 41 (29.7%) with stage 1, six (4.4%) with stage 2, and eight (5.8%) with stage 3 acute kidney injury. Cardiopulmonary bypass was strongly associated with a higher risk of any acute kidney injury (adjusted odds ratio, 4.8 [95% CI, 1.4-16.0]; p = 0.01) but not stage 2/3 acute kidney injury. Lower renal perfusion pressure on the day of surgery (postoperative day, 0) was associated with a higher risk of stage 2/3 acute kidney injury (adjusted odds ratio, 1.2 [95% CI, 1.0-1.5]; p = 0.03). Higher vasoactive-inotropic score on postoperative day 0 was associated with a higher risk for stage 2/3 acute kidney injury (adjusted odds ratio, 1.9 [95% CI, 1.0-3.4]; p = 0.04). Stage 2/3 acute kidney injury was associated with longer cardiovascular ICU length of stay (mean, 7.3 greater d [95% CI, 3.4-11.3]; p < 0.001) and hospital postoperative length of stay (mean, 6.4 greater d [95% CI, 0.06-12.5]; p = 0.04). Postoperative acute kidney injury in patients undergoing the extracardiac Fontan operation is common and is associated with lower postoperative renal perfusion pressure and higher vasoactive-inotropic score. Cardiopulmonary bypass was strongly associated with any acute kidney injury, although not stage 2/3 acute kidney injury. Stage 2/3 acute kidney injury is a compelling risk factor for longer cardiovascular ICU

Management of acute traumatic spinal cord injuries.

PubMed

Shank, C D; Walters, B C; Hadley, M N

2017-01-01

Acute traumatic spinal cord injury (SCI) is a devastating disease process affecting tens of thousands of people across the USA each year. Despite the increase in primary prevention measures, such as educational programs, motor vehicle speed limits, automobile running lights, and safety technology that includes automobile passive restraint systems and airbags, SCIs continue to carry substantial permanent morbidity and mortality. Medical measures implemented following the initial injury are designed to limit secondary insult to the spinal cord and to stabilize the spinal column in an attempt to decrease devastating sequelae. This chapter is an overview of the contemporary management of an acute traumatic SCI patient from the time of injury through the stay in the intensive care unit. We discuss initial triage, immobilization, and transportation of the patient by emergency medical services personnel to a definitive treatment facility. Upon arrival at the emergency department, we review initial trauma protocols and the evidence-based recommendations for radiographic evaluation of the patient's vertebral column. Finally, we outline closed cervical spine reduction and various aggressive medical therapies aimed at improving neurologic outcome. © 2017 Elsevier B.V. All rights reserved.

Management of acute unstable acromioclavicular joint injuries.

PubMed

Cisneros, Luis Natera; Reiriz, Juan Sarasquete

2016-12-01

Surgical management of acute unstable acromioclavicular joint injuries should be focused on realigning the torn ends of the ligaments to allow for healing potential. The most widely utilized treatment methods incorporate the use of metal hardware, which can alter the biomechanics of the acromioclavicular joint. This leads to a second surgical procedure for hardware removal once the ligaments have healed. Patients with unstable acromioclavicular joint injuries managed with arthroscopy-assisted procedures have shown good and excellent clinical outcomes, without the need for a second operation. These procedures incorporate a coracoclavicular suspension device aimed to function as an internal brace, narrowing the coracoclavicular space thus allowing for healing of the torn coracoclavicular ligaments. The lesser morbidity of a minimally invasive approach and the possibility to diagnose and treat concomitant intraarticular injuries; no obligatory implant removal, and the possibility of having a straight visualization of the inferior aspect of the base of the coracoid (convenient when placing coracoclavicular fixation systems) are the main advantages of the arthroscopic approach over classic open procedures. This article consists on a narrative review of the literature in regard to the management of acute acromioclavicular joint instability.

The pattern of early lung parenchymal and air space injury following acute blood loss.

PubMed

Younger, J G; Taqi, A S; Jost, P F; Till, G O; Johnson, K J; Stern, S A; Hirschl, R B

1998-07-01

Acute lung injury is a frequent clinical occurrence following blood loss and trauma. The nature of this injury remains poorly understood. To examine the relative parenchymal and intra-alveolar distribution of inflammation in a rat model of hemorrhage and resuscitation. Rats were anesthetized and subjected to hemorrhage followed by resuscitation with shed blood and saline. Myeloperoxidase activity of lung homogenates and cytology of bronchoalveolar lavage fluid were used to measure total lung and intra-alveolar neutrophil invasion. Extravasation of i.v.-administered [125I]-albumin was used to determine total lung and alveolar permeability. Permeability results were analyzed using their base-10 logarithmic transformations. 86 animals were studied. Whole-lung myeloperoxidase activity was increased (control = 0.34 +/- 0.16 units, injured = 0.84 +/- 0.43 units, p < 0.01), while there was no difference in intra-alveolar leukocyte counts (injured = 1.85 +/- 1.30 x 10(5)/mL, control = 2.44 +/- 1.75 x 10(5)/mL, p = 0.40), suggesting that the cellular component of the injury was more severe in the intravascular and interstitial spaces. There was a strong trend toward increased permeability in the interstitial compartment, and a significant increase in permeability in the intra-alveolar compartment (whole-lung permeability: control = -0.27 +/- 0.19 units, injured = 0.10 +/- 0.55 units, p = 0.06; alveolar permeability: control = -2.00 +/- 0.47 units, injured = -1.32 +/- 0.49 units, p < 0.01), suggesting that the loss of integrity to macromolecules was not limited to the interstitium. Hemorrhage and resuscitation resulted in an acute lung injury characterized by extravasation of intravascular protein into both the interstitium and the intra-alveolar space. Neutrophil invasion of the lung was demonstrable only in the interstitial compartment.

Prediction of acute kidney injury within 30 days of cardiac surgery.

PubMed

Ng, Shu Yi; Sanagou, Masoumeh; Wolfe, Rory; Cochrane, Andrew; Smith, Julian A; Reid, Christopher Michael

2014-06-01

To predict acute kidney injury after cardiac surgery. The study included 28,422 cardiac surgery patients who had had no preoperative renal dialysis from June 2001 to June 2009 in 18 hospitals. Logistic regression analyses were undertaken to identify the best combination of risk factors for predicting acute kidney injury. Two models were developed, one including the preoperative risk factors and another including the pre-, peri-, and early postoperative risk factors. The area under the receiver operating characteristic curve was calculated, using split-sample internal validation, to assess model discrimination. The incidence of acute kidney injury was 5.8% (1642 patients). The mortality for patients who experienced acute kidney injury was 17.4% versus 1.6% for patients who did not. On validation, the area under the curve for the preoperative model was 0.77, and the Hosmer-Lemeshow goodness-of-fit P value was .06. For the postoperative model area under the curve was 0.81 and the Hosmer-Lemeshow P value was .6. Both models had good discrimination and acceptable calibration. Acute kidney injury after cardiac surgery can be predicted using preoperative risk factors alone or, with greater accuracy, using pre-, peri-, and early postoperative risk factors. The ability to identify high-risk individuals can be useful in preoperative patient management and for recruitment of appropriate patients to clinical trials. Prediction in the early stages of postoperative care can guide subsequent intensive care of patients and could also be the basis of a retrospective performance audit tool. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Necroptosis in Acute Kidney Injury.

PubMed

Anders, Hans-Joachim

2018-05-31

Regulated necrosis is an expanding research field with important implications for acute kidney injury (AKI). A focused review of the evolving evidence for necroptosis in AKI, one of several forms of regulated necrosis defines the known and unknown. A literature search was performed in PUBMED and ScienceDirect between January 1957 and April 2018 using the following keywords: "acute kidney injury," "necrosis," "necroptosis," "necroinflammation." The necroptosis signaling cascade involves a number of proteins including receptor-interacting protein-1 (RIPK1), RIPK3, and mixed lineage kinase domain-like pseudokinase (MLKL) as well as the MLKL regulator RGMb. The existing experimental evidence in AKI based on mice with genetic deletions of these proteins, more or less specific inhibitory compounds, and diverse experimental AKI models is reviewed. There is broad consistency suggesting a role for necroptosis in AKI, but some studies report divergent evidence potentially relating to the specific model used and the time point of analysis. Mlkl-deficient mice are currently the most specific and reliable experimental tool to study necroptosis in vivo (in kidney disease). The clinical potential of necroptosis inhibition in AKI is to be evaluated, but conceptual problems in AKI definitions and in complex clinical scenarios remain a concern. © 2018 S. Karger AG, Basel.

Obeticholic acid protects against carbon tetrachloride-induced acute liver injury and inflammation.

PubMed

Zhang, Da-Gang; Zhang, Cheng; Wang, Jun-Xian; Wang, Bi-Wei; Wang, Hua; Zhang, Zhi-Hui; Chen, Yuan-Hua; Lu, Yan; Tao, Li; Wang, Jian-Qing; Chen, Xi; Xu, De-Xiang

2017-01-01

The farnesoid X receptor (FXR) is a ligand-activated transcription factor that plays important roles in regulating bile acid homeostasis. The aim of the present study was to investigate the effects of obeticholic acid (OCA), a novel synthetic FXR agonist, carbon tetrachloride (CCl 4 )-induced acute liver injury. Mice were intraperitoneally injected with CCl 4 (0.15ml/kg). In CCl 4 +OCA group, mice were orally with OCA (5mg/kg) 48, 24 and 1h before CCl 4 . As expected, hepatic FXR was activated by OCA. Interestingly, OCA pretreatment alleviated CCl 4 -induced elevation of serum ALT and hepatic necrosis. Moreover, OCA pretreatment inhibited CCl 4 -induced hepatocyte apoptosis. Additional experiment showed that OCA inhibits CCl 4 -induced hepatic chemokine gene Mcp-1, Mip-2 and Kc. Moreover, OCA inhibits CCl 4 -induced hepatic pro-inflammatory gene Tnf-α and Il-1β. By contrast, OCA pretreatment elevated hepatic anti-inflammatory gene Il-4. Further analysis showed that OCA pretreatment inhibited hepatic IκB phosphorylation and blocked nuclear translocation of NF-κB p65 and p50 subunits during CCl 4 -induced acute liver injury. In addition, OCA pretreatment inhibited hepatic Akt, ERK and p38 phosphorylation in CCl 4 -induced acute liver injury. These results suggest that OCA protects against CCl 4 -induced acute liver injury and inflammation. Synthetic FXR agonists may be effective antidotes for hepatic inflammation during acute liver injury. Copyright © 2016 Elsevier Inc. All rights reserved.

Contribution of neutrophils to acute lung injury.

PubMed

Grommes, Jochen; Soehnlein, Oliver

2011-01-01

Treatment of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), remain unsolved problems of intensive care medicine. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. Lung edema, endothelial and epithelial injury are accompanied by an influx of neutrophils into the interstitium and broncheoalveolar space. Hence, activation and recruitment of neutrophils are regarded to play a key role in progression of ALI/ARDS. Neutrophils are the first cells to be recruited to the site of inflammation and have a potent antimicrobial armour that includes oxidants, proteinases and cationic peptides. Under pathological circumstances, however, unregulated release of these microbicidal compounds into the extracellular space paradoxically can damage host tissues. This review focuses on the mechanisms of neutrophil recruitment into the lung and on the contribution of neutrophils to tissue damage in ALI.

YKL-40 expression in CD14+ liver cells in acute and chronic injury

PubMed Central

Pizano-Martínez, Oscar; Yañez-Sánchez, Irinea; Alatorre-Carranza, Pilar; Miranda-Díaz, Alejandra; Ortiz-Lazareno, Pablo C; García-Iglesias, Trinidad; Daneri-Navarro, Adrian; Mercado, Mónica Vázquez-Del; Fafutis-Morris, Mary; Delgado-Rizo, Vidal

2011-01-01

AIM: To demonstrate that CD14+ cells are an important source of the growth factor YKL-40 in acute and chronic liver damage. METHODS: Rats were inoculated with one dose of CCl4 to induce acute damage. Liver biopsies were obtained at 0, 6, 12, 24, 48 and 72 h. For chronic damage, CCl4 was administered three days per week for 6 or 8 wk. Tissue samples were collected, and cellular populations were isolated by liver digestion and purified by cell sorting. YKL-40 mRNA and protein expression were evaluated by real-time polymerase chain reaction and western blot. RESULTS: Acute liver damage induced a rapid increase of YKL-40 mRNA beginning at 12 h. Expression peaked at 24 h, with a 26-fold increase over basal levels. By 72 h however, YKL-40 expression levels had nearly returned to control levels. On the other hand, chronic damage induced a sustained increase in YKL-40 expression, with 7- and 9-fold higher levels at 6 and 8 wk, respectively. The pattern of YKL-40 expression in different subpopulations showed that CD14+ cells, which include Kupffer cells, are a source of YKL-40 after acute damage at 72 h [0.09 relative expression units (REU)] as well as after chronic injury at 6 wk (0.11 REU). Hepatocytes, in turn, accounted for 0.06 and 0.01 REU after 72 h (acute) or 6 wk (chronic), respectively. The rest of the CD14- cells (including T lymphocytes, B lymphocytes, natural killer and natural killer T cells) yielded 0.07 and 0.15 REU at 72 h and 6 wk, respectively. YKL-40 protein expression in liver was detected at 72 h as well as 6 and 8 wk, with the highest expression relative to controls (11-fold; P ≤ 0.05) seen at 6 wk. Macrophages were stimulated by lipopolysaccharide. We demonstrate that under these conditions, these cells showed maximum expression of YKL-40 at 12 h, with P < 0.05 compared with controls. CONCLUSION: Hepatic CD14+ cells are an YKL-40 mRNA and protein source in acute and chronic liver injury, with expression patterns similar to growth factors implicated

Energy drink-induced acute kidney injury.

PubMed

Greene, Elisa; Oman, Kristy; Lefler, Mary

2014-10-01

To report a case of acute renal failure possibly induced by Red Bull. A 40-year-old man presented with various complaints, including a recent hypoglycemic episode. Assessment revealed that serum creatinine was elevated at 5.5 mg/dL, from a baseline of 0.9 mg/dL. An interview revealed a 2- to 3-week history of daily ingestion of 100 to 120 oz of Red Bull energy drink. Resolution of renal dysfunction occurred within 2 days of discontinuation of Red Bull and persisted through 10 months of follow-up. Rechallenge was not attempted. Energy-drink-induced renal failure has been reported infrequently. We identified 2 case reports via a search of MEDLINE, one of which occurred in combination with alcohol and the other of which was not available in English. According to the Food and Drug Administration's (FDA's) Center for Food Safety and Applied Nutrition Adverse Event Reporting System, between 2004 and 2012, the FDA has received 166 reports of adverse events associated with energy drink consumption. Only 3 of the 166 (0.18%) described renal failure, and none were reported with Red Bull specifically. A defined mechanism for injury is unknown. Assessment of the Naranjo adverse drug reaction probability scale indicates a probable relationship between the development of acute renal failure and Red Bull ingestion in our patient. Acute kidney injury has rarely been reported with energy drink consumption. Our report describes the first English language report of acute renal failure occurring in the context of ingestion of large quantities of energy drink without concomitant alcohol. © The Author(s) 2014.

A Score for Predicting Acute Kidney Injury After Coronary Artery Bypass Graft Surgery in an Asian Population.

PubMed

Mithiran, Harish; Kunnath Bonney, Glenn; Bose, Saideep; Subramanian, Srinivas; Zhe Yan, Zan Ng; Zong En, Seth Yeak; Papadimas, Evangelos; Chauhan, Ishaan; MacLaren, Graeme; Kofidis, Theodoros

2016-10-01

To develop a scoring system to predict acute kidney injury in Asian patients after coronary artery bypass grafting. A retrospective analysis of data collected in an institutional cardiac database. A tertiary academic hospital in a large metropolitan city. The study comprised 954 patients with coronary artery disease. All patients underwent coronary artery bypass surgery with cardiopulmonary bypass but did not undergo any other concomitant procedures. The main outcome measured was acute kidney injury as defined by the Acute Kidney Injury Network criteria. The following 6 clinical variables were independent predictors of kidney injury: age>60 years, diabetes requiring insulin, estimated glomerular filtration rate<60 mL/min/1.73 m(2), ejection fraction<40%, cardiopulmonary bypass time>140 minutes, and aortic cross-clamp time>100 minutes. These variables were used to develop the Singapore Acute Kidney Injury score. The Singapore Acute Kidney Injury score is a simple way to predict, at the time of admission to the intensive care unit, an Asian patient's risk of developing acute kidney injury after coronary artery bypass surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Calcium-binding proteins annexin A2 and S100A6 are sensors of tubular injury and recovery in acute renal failure.

PubMed

Cheng, Chao-Wen; Rifai, Abdalla; Ka, Shuk-Man; Shui, Hao-Ai; Lin, Yuh-Feng; Lee, Wei-Hwa; Chen, Ann

2005-12-01

Rise in cellular calcium is associated with acute tubular necrosis, the most common cause of acute renal failure (ARF). The mechanisms that calcium signaling induce in the quiescent tubular cells to proliferate and differentiate during acute tubular necrosis have not been elucidated. Acute tubular necrosis induced in mice by single intravenous injection of uranyl nitrate and examined after 1, 3, 7, and 14 days. Renal function was monitored and kidneys were evaluated by histology, immunohistochemistry, Western blotting, in situ hybridization, and real-time reverse transcription-polymerase chain reaction (RT-PCR). Models of folic acid induced-ARF and ischemic/reperfusion (I/R) injury were similarly investigated. Analysis of mRNA expression of intracellular calcium and phospholipid-binding proteins demonstrated selective expression of S100A6 and Annexin A2 (Anxa2) in the renal cortex with marked elevation on day 3, and gradually decline on day 7 and further attenuation on day 14. Similarly, the expression of both proteins, as demonstrated by immunohistochemistry and Western blot analysis, was increased and reached the peak level on day 7 and then gradually declined by day 14. Vimentin, a marker of dedifferentiated cells, was highly expressed during the recovery phase. Combined in situ hybridization immunohistochemistry revealed colocalization of both S100A6 and Anxa2 with proliferating cell nuclear antigen (PCNA). The universality of this phenomenon was confirmed in two other mouse acute tubular necrosis models, the ischemic-reperfusion injury and folic acid-induced ARF. Collectively, these findings demonstrate that S100A6 and Anxa2 expression, initiated in response to tubular injury, persist in parallel throughout the recovery process of tubular cells in acute renal failure.

Performance of an automated electronic acute lung injury screening system in intensive care unit patients.

PubMed

Koenig, Helen C; Finkel, Barbara B; Khalsa, Satjeet S; Lanken, Paul N; Prasad, Meeta; Urbani, Richard; Fuchs, Barry D

2011-01-01

Lung protective ventilation reduces mortality in patients with acute lung injury, but underrecognition of acute lung injury has limited its use. We recently validated an automated electronic acute lung injury surveillance system in patients with major trauma in a single intensive care unit. In this study, we assessed the system's performance as a prospective acute lung injury screening tool in a diverse population of intensive care unit patients. Patients were screened prospectively for acute lung injury over 21 wks by the automated system and by an experienced research coordinator who manually screened subjects for enrollment in Acute Respiratory Distress Syndrome Clinical Trials Network (ARDSNet) trials. Performance of the automated system was assessed by comparing its results with the manual screening process. Discordant results were adjudicated blindly by two physician reviewers. In addition, a sensitivity analysis using a range of assumptions was conducted to better estimate the system's performance. The Hospital of the University of Pennsylvania, an academic medical center and ARDSNet center (1994-2006). Intubated patients in medical and surgical intensive care units. None. Of 1270 patients screened, 84 were identified with acute lung injury (incidence of 6.6%). The automated screening system had a sensitivity of 97.6% (95% confidence interval, 96.8-98.4%) and a specificity of 97.6% (95% confidence interval, 96.8-98.4%). The manual screening algorithm had a sensitivity of 57.1% (95% confidence interval, 54.5-59.8%) and a specificity of 99.7% (95% confidence interval, 99.4-100%). Sensitivity analysis demonstrated a range for sensitivity of 75.0-97.6% of the automated system under varying assumptions. Under all assumptions, the automated system demonstrated higher sensitivity than and comparable specificity to the manual screening method. An automated electronic system identified patients with acute lung injury with high sensitivity and specificity in diverse

Acoustically detectable cellular-level lung injury induced by fluid mechanical stresses in microfluidic airway systems.

PubMed

Huh, Dongeun; Fujioka, Hideki; Tung, Yi-Chung; Futai, Nobuyuki; Paine, Robert; Grotberg, James B; Takayama, Shuichi

2007-11-27

We describe a microfabricated airway system integrated with computerized air-liquid two-phase microfluidics that enables on-chip engineering of human airway epithelia and precise reproduction of physiologic or pathologic liquid plug flows found in the respiratory system. Using this device, we demonstrate cellular-level lung injury under flow conditions that cause symptoms characteristic of a wide range of pulmonary diseases. Specifically, propagation and rupture of liquid plugs that simulate surfactant-deficient reopening of closed airways lead to significant injury of small airway epithelial cells by generating deleterious fluid mechanical stresses. We also show that the explosive pressure waves produced by plug rupture enable detection of the mechanical cellular injury as crackling sounds.

Acute kidney injury and edaravone in acute ischemic stroke: the Fukuoka Stroke Registry.

PubMed

Kamouchi, Masahiro; Sakai, Hironori; Kiyohara, Yutaka; Minematsu, Kazuo; Hayashi, Kunihiko; Kitazono, Takanari

2013-11-01

A free radical scavenger, edaravone, which has been used for the treatment of ischemic stroke, was reported to cause acute kidney injury (AKI) as a fatal adverse event. The aim of the present study was to clarify whether edaravone is associated with AKI in patients with acute ischemic stroke. From the Fukuoka Stroke Registry database, 5689 consecutive patients with acute ischemic stroke who were hospitalized within 24 hours of the onset of symptoms were included in this study. A logistic regression analysis for the Fukuoka Stroke Registry cohort was done to identify the predictors for AKI. A propensity score-matched nested case-control study was also performed to elucidate any association between AKI and edaravone. Acute kidney injury occurred in 128 of 5689 patients (2.2%) with acute ischemic stroke. A multivariate analysis revealed that the stroke subtype, the basal serum creatinine level, and the presence of infectious complications on admission were each predictors of developing AKI. In contrast, a free radical scavenger, edaravone, reduced the risk of developing AKI (multivariate-adjusted odds ratio [OR] .45, 95% confidence interval [CI] .30-.67). Propensity score-matched case-control study confirmed that edaravone use was negatively associated with AKI (propensity score-adjusted OR .46, 95% CI .29-.74). Although AKI has a significant impact on the clinical outcome of hospital inpatients, edaravone has a protective effect against the development of AKI in patients with acute ischemic stroke. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

High risk of rhabdomyolysis and acute kidney injury after traumatic limb compartment syndrome.

PubMed

Tsai, Wei-Hsuan; Huang, Shih-Tsai; Liu, Wen-Chung; Chen, Lee-Wei; Yang, Kuo-Chung; Hsu, Kuei-Chang; Lin, Cheng-Ta; Ho, Yen-Yi

2015-05-01

Rhabdomyolysis often occurs after traumatic compartment syndrome, and high morbidity and mortality have been reported with the acute kidney injury that develops subsequently. We focused on the risk factors for rhabdomyolysis and acute kidney injury in patients with traumatic compartment syndrome. We also analyzed the relation between renal function and rhabdomyolysis in these patients. A retrospective chart review was conducted from January 2006 to March 2012. Inpatients with traumatic compartment syndrome were included. We evaluated patients' demographics, history of illicit drugs use or alcohol consumption, mechanism of injury, symptoms, serum creatine kinase levels, and kidney function. A total of 52 patients with a mean age of 40.9 years were included; 23 patients had rhabdomyolysis (44.2%), of which 9 patients developed acute kidney injury (39.1%). Significant predictive factors for rhabdomyolysis were history of illicit drugs or alcohol use (P=0.039; odds ratio, 5.91) and ischemic injury (P=0.005). We found a moderate correlation between serum creatine kinase levels and serum creatinine levels (R=0.57; P<0.0001). The correlation coefficient (R) between serum creatine kinase levels and the estimated creatinine clearance rate was -0.45. Rhabdomyolysis was a predisposing factor for acute kidney injury (P=0.011; odds ratio, 8.68). Four patients with rhabdomyolysis required a short period of renal replacement therapy. A high percentage of patients with traumatic compartment syndrome developed rhabdomyolysis (44.2%). Patients with rhabdomyolysis had a higher possibility of developing acute kidney injury (39.1%), and rhabdomyolysis was correlated to renal function. Early diagnosis, frequent monitoring, and aggressive treatment are suggested once compartment syndrome is suspected. The overall prognosis is good with early diagnosis and proper treatment.

Mild Hypothermia and Acute Kidney Injury in Liver Transplantation

ClinicalTrials.gov

2018-06-18

Cirrhosis; End Stage Liver Disease; Acute Kidney Injury; Liver Transplant; Complications; Chronic Kidney Diseases; Hepatitis c; Hepatitis B; NASH - Nonalcoholic Steatohepatitis; Alcoholic Cirrhosis; Hepatocellular Carcinoma

Acetaminophen-induced acute liver injury in HCV transgenic mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle

2013-01-15

The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wildmore » type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.« less

The role of autophagy in acute brain injury: A state of flux?

PubMed

Wolf, Michael S; Bayır, Hülya; Kochanek, Patrick M; Clark, Robert S B

2018-04-26

It is established that increased autophagy is readily detectable after various types of acute brain injury, including trauma, focal and global cerebral ischemia. What remains controversial, however, is whether this heightened detection of autophagy in brain represents a homeostatic or pathologic process, or an epiphenomenon. The ultimate role of autophagy after acute brain injury likely depends upon: 1) the degree of brain injury and the overall autophagic burden; 2) the capacity of individual cell types to ramp up autophagic flux; 3) the local redox state and signaling of parallel cell death pathways; 4) the capacity to eliminate damage associated molecular patterns and toxic proteins and metabolites both intra- and extracellularly; and 5) the timing of the pro- or anti-autophagic intervention. In this review, we attempt to reconcile conflicting studies that support both a beneficial and detrimental role for autophagy in models of acute brain injury. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of Hypercapnia on Acute Cellular Rejection after Lung Transplantation in Rats.

PubMed

Tan, Jing; Liu, Yanhong; Jiang, Tao; Wang, Ling; Zhao, Can; Shen, Dongfang; Cui, Xiaoguang

2018-01-01

Hypercapnia alleviates pulmonary ischemia-reperfusion injury, regulates T lymphocytes, and inhibits immune reaction. This study aimed to evaluate the effect of hypercapnia on acute cellular rejection in a rat lung transplantation model. Recipient rats in sham-operated (Wistar), isograft (Wistar to Wistar), and allograft (Sprague-Dawley to Wistar) groups were ventilated with 50% oxygen, whereas rats in the hypercapnia (Sprague-Dawley to Wistar) group were administered 50% oxygen and 8% carbon dioxide for 90 min during reperfusion (n = 8). Recipients were euthanized 7 days after transplantation. The hypercapnia group showed a higher oxygenation index (413 ± 78 vs. 223 ± 24), lower wet weight-to-dry weight ratio (4.23 ± 0.54 vs. 7.04 ± 0.80), lower rejection scores (2 ± 1 vs. 4 ± 1), and lower apoptosis index (31 ± 6 vs. 57 ± 4) as compared with the allograft group. The hypercapnia group showed lower CD8 (17 ± 4 vs. 31 ± 3) and CD68 (24 ± 3 vs. 43 ± 2), lower CD8 T cells (12 ± 2 vs. 35 ± 6), and higher CD4/CD8 ratio (2.2 ± 0.6 vs. 1.1 ± 0.4) compared to the allograft group. Tumor necrosis factor-α (208 ± 40 vs. 292 ± 49), interleukin-2 (30.6 ± 6.7 vs. 52.7 ± 8.3), and interferon-γ (28.1 ± 4.9 vs. 62.7 ± 10.1) levels in the hypercapnia group were lower than those in allograft group. CD4, CD4 T cells, and interleukin-10 levels were similar between groups. Hypercapnia ameliorated acute cellular rejection in a rat lung transplantation model.

Early magnetic resonance imaging in acute knee injury: a cost analysis.

PubMed

Patel, Nirav K; Bucknill, Andrew; Ahearne, David; Denning, Janet; Desai, Kailash; Watson, Martin

2012-06-01

Acute knee injury is common, and MRI is often only used when non-operative management fails because of limited availability. We investigated whether early MRI in acute knee injury is more clinically and cost-effective compared to conventional physiotherapy and reassessment. All patients with acute indirect soft tissue knee injury referred to fracture clinic were approached. Recruited patients were randomised to either the MRI group: early MRI within 2 weeks or the control group: conventional management with physiotherapy. Patients were assessed in clinic initially, at 2 weeks and 3 months post-injury. Management costs were calculated for all patients until surgical treatment or discharge. Forty-six patients were recruited: 23 in the MRI and 23 in the control group. Male sex and mean age were similar in the two groups. The total management cost of the MRI group was £16,127 and control group was £16,170, with a similar mean cost per patient (NS). The MRI group had less mean physiotherapy (2.5 ± 1.9 vs. 5.1 ± 3.5, p < 0.01) and outpatient appointments (NS). Median time to surgery and time off work was less in the MRI group (NS). The MRI group had less pain (p < 0.05), less activity limitation (p = 0.04) and better satisfaction (p = 0.04). Early MRI in acute knee injury facilitates faster diagnosis and management of internal derangement at a cost comparable to conventional treatment. Moreover, patients had significantly less time off work with improved pain, activity limitation and satisfaction scores. II.

Acute Myocardial Ischemia: Cellular Mechanisms Underlying ST Segment Elevation

PubMed Central

Di Diego, José M.; Antzelevitch, Charles

2014-01-01

The electrocardiogram (ECG) is an essential tool for the diagnosis of acute myocardial ischemia in the emergency department, as well as for that of an evolving acute myocardial infarction (AMI). Changes in the surface ECG in leads whose positive poles face the ischemic region are known to be related to injury currents flowing across the boundaries between the ischemic and the surrounding normal myocardium. Although experimental studies have also shown an endocardium to epicardium differential sensitivity to the effect of acute ischemia, the important contribution of this transmural heterogeneous response to the changes observed in the surface ECG are less appreciated by the clinical cardiologist. This review briefly discusses our current knowledge regarding the electrophysiology of the ischemic myocardium focusing primarily on the electrophysiologic changes underlying the ECG alterations observed at the onset of a transmural AMI. PMID:24742586

Oleic acid induces acute pulmonary injury and inflammation in vivo

EPA Science Inventory

Oleic acid (OA) is frequently used as a representative fatty acid, and is found in meat-cooking fumes and biodiesel exhaust. Vascular damage and acute lung injury has been observed with OA vascular infusion in models of acute respiratory distress, but it is not yet established ...

Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury

PubMed Central

Gralinski, Lisa E.; Bankhead, Armand; Jeng, Sophia; Menachery, Vineet D.; Proll, Sean; Belisle, Sarah E.; Matzke, Melissa; Webb-Robertson, Bobbie-Jo M.; Luna, Maria L.; Shukla, Anil K.; Ferris, Martin T.; Bolles, Meagan; Chang, Jean; Aicher, Lauri; Waters, Katrina M.; Smith, Richard D.; Metz, Thomas O.; Law, G. Lynn; Katze, Michael G.; McWeeney, Shannon; Baric, Ralph S.

2013-01-01

ABSTRACT Systems biology offers considerable promise in uncovering novel pathways by which viruses and other microbial pathogens interact with host signaling and expression networks to mediate disease severity. In this study, we have developed an unbiased modeling approach to identify new pathways and network connections mediating acute lung injury, using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model pathogen. We utilized a time course of matched virologic, pathological, and transcriptomic data within a novel methodological framework that can detect pathway enrichment among key highly connected network genes. This unbiased approach produced a high-priority list of 4 genes in one pathway out of over 3,500 genes that were differentially expressed following SARS-CoV infection. With these data, we predicted that the urokinase and other wound repair pathways would regulate lethal versus sublethal disease following SARS-CoV infection in mice. We validated the importance of the urokinase pathway for SARS-CoV disease severity using genetically defined knockout mice, proteomic correlates of pathway activation, and pathological disease severity. The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV. PMID:23919993

Vildagliptin-induced acute lung injury: a case report.

PubMed

Ohara, Nobumasa; Kaneko, Masanori; Sato, Kazuhiro; Maruyama, Ryoko; Furukawa, Tomoyasu; Tanaka, Junta; Kaneko, Kenzo; Kamoi, Kyuzi

2016-08-12

Dipeptidyl peptidase-4 inhibitors are a class of oral hypoglycemic drugs and are used widely to treat type 2 diabetes mellitus in many countries. Adverse effects include nasopharyngitis, headache, elevated serum pancreatic enzymes, and gastrointestinal symptoms. In addition, a few cases of interstitial pneumonia associated with their use have been reported in the Japanese literature. Here we describe a patient who developed drug-induced acute lung injury shortly after the administration of the dipeptidyl peptidase-4 inhibitor vildagliptin. A 38-year-old Japanese woman with diabetes mellitus developed acute respiratory failure 1 day after administration of vildagliptin. Chest computed tomography revealed nonsegmental ground-glass opacities in her lungs. There was no evidence of bacterial pneumonia or any other cause of her respiratory manifestations. After discontinuation of vildagliptin, she recovered fully from her respiratory disorder. She received insulin therapy for her diabetes mellitus, and her subsequent clinical course has been uneventful. The period of drug exposure in previously reported cases of patients with drug-induced interstitial pneumonia caused by dipeptidyl peptidase-4 inhibitor varied from several days to over 6 months. In the present case, our patient developed interstitial pneumonia only 1 day after the administration of vildagliptin. The precise mechanism of her vildagliptin-induced lung injury remains uncertain, but physicians should consider that dipeptidyl peptidase-4 inhibitor-induced lung injury, although rare, may appear acutely, even within days after administration of this drug.

Reducing Acute Kidney Injury Due to Contrast Material: How Nurses Can Improve Patient Safety.

PubMed

Lambert, Peggy; Chaisson, Kristine; Horton, Susan; Petrin, Carmen; Marshall, Emily; Bowden, Sue; Scott, Lynn; Conley, Sheila; Stender, Janette; Kent, Gertrude; Hopkins, Ellen; Smith, Brian; Nicholson, Anita; Roy, Nancy; Homsted, Brenda; Downs, Cindy; Ross, Cathy S; Brown, Jeremiah

2017-02-01

Acute kidney injury due to contrast material occurs in 3% to 15% of the 2 million cardiac catheterizations done in the United States each year. To reduce acute kidney injury due to contrast material after cardiovascular interventional procedures. Nurse leaders in the Northern New England Cardiovascular Disease Study Group, a 10-center quality improvement consortium in Maine, New Hampshire, and Vermont, formed a nursing task force to reduce acute kidney injury due to contrast material after cardiovascular interventional procedures. Data were prospectively collected January 1, 2007, through June 30, 2012, on consecutive nonemergent patients (n = 20 147) undergoing percutaneous coronary interventions. Compared with baseline rates, adjusted rates of acute kidney injury among the 10 centers were significantly reduced by 21% and by 28% in patients with baseline estimated glomerular filtration rate less than 60 mL/min per 1.73 m 2 . Key qualitative system factors associated with improvement included use of multidisciplinary teams, standardized fluid orders, use of an intravenous fluid bolus, patient education about oral hydration, and limiting the volume of contrast material. Standardization of evidence-based best practices in nursing care may reduce the incidence of acute kidney injury due to contrast material. ©2017 American Association of Critical-Care Nurses.

Perioperative aspirin and clonidine and risk of acute kidney injury: a randomized clinical trial.

PubMed

Garg, Amit X; Kurz, Andrea; Sessler, Daniel I; Cuerden, Meaghan; Robinson, Andrea; Mrkobrada, Marko; Parikh, Chirag R; Mizera, Richard; Jones, Philip M; Tiboni, Maria; Font, Adrià; Cegarra, Virginia; Gomez, Maria Fernanda Rojas; Meyhoff, Christian S; VanHelder, Tomas; Chan, Matthew T V; Torres, David; Parlow, Joel; Clanchet, Miriam de Nadal; Amir, Mohammed; Bidgoli, Seyed Javad; Pasin, Laura; Martinsen, Kristian; Malaga, German; Myles, Paul; Acedillo, Rey; Roshanov, Pavel S; Walsh, Michael; Dresser, George; Kumar, Priya; Fleischmann, Edith; Villar, Juan Carlos; Painter, Thomas; Biccard, Bruce; Bergese, Sergio; Srinathan, Sadeesh; Cata, Juan P; Chan, Vincent; Mehra, Bhupendra; Wijeysundera, Duminda N; Leslie, Kate; Forget, Patrice; Whitlock, Richard; Yusuf, Salim; Devereaux, P J

2014-12-03

Acute kidney injury, a common complication of surgery, is associated with poor outcomes and high health care costs. Some studies suggest aspirin or clonidine administered during the perioperative period reduces the risk of acute kidney injury; however, these effects are uncertain and each intervention has the potential for harm. To determine whether aspirin compared with placebo, and clonidine compared with placebo, alters the risk of perioperative acute kidney injury. A 2 × 2 factorial randomized, blinded, clinical trial of 6905 patients undergoing noncardiac surgery from 88 centers in 22 countries with consecutive patients enrolled between January 2011 and December 2013. Patients were assigned to take aspirin (200 mg) or placebo 2 to 4 hours before surgery and then aspirin (100 mg) or placebo daily up to 30 days after surgery, and were assigned to take oral clonidine (0.2 mg) or placebo 2 to 4 hours before surgery, and then a transdermal clonidine patch (which provided clonidine at 0.2 mg/d) or placebo patch that remained until 72 hours after surgery. Acute kidney injury was primarily defined as an increase in serum creatinine concentration from the preoperative concentration by either an increase of 0.3 mg/dL or greater (≥26.5 μmol/L) within 48 hours of surgery or an increase of 50% or greater within 7 days of surgery. Aspirin (n = 3443) vs placebo (n = 3462) did not alter the risk of acute kidney injury (13.4% vs 12.3%, respectively; adjusted relative risk, 1.10; 95% CI, 0.96-1.25). Clonidine (n = 3453) vs placebo (n = 3452) did not alter the risk of acute kidney injury (13.0% vs 12.7%, respectively; adjusted relative risk, 1.03; 95% CI, 0.90-1.18). Aspirin increased the risk of major bleeding. In a post hoc analysis, major bleeding was associated with a greater risk of subsequent acute kidney injury (23.3% when bleeding was present vs 12.3% when bleeding was absent; adjusted hazard ratio, 2.20; 95% CI, 1.72-2.83). Similarly, clonidine

Risk factors of acute and overuse musculoskeletal injuries among young conscripts: a population-based cohort study.

PubMed

Taanila, Henri; Suni, Jaana H; Kannus, Pekka; Pihlajamäki, Harri; Ruohola, Juha-Petri; Viskari, Jarmo; Parkkari, Jari

2015-05-01

Military service in Finland is compulsory for all male citizens and annually about 80% of 19-year-old men enter into the service. The elevated risk for many chronic diseases and loss of function among those who are inactive and unfit can be often detected already in youth. On the other hand, activity-induced injuries among young are true public health issue. The purpose of the present prospective cohort follow-up study was to evaluate predictive associations between acute or overuse injuries and their various intrinsic risk factors. Four successive cohorts of conscripts who formed a representative sample of Finnish young men were followed for 6 months. At the beginning of the service, the risk factors of injuries were measured and recorded and then the acute and overuse injuries treated at the garrison clinic were identified. Predictive associations between injuries and their risk factors were examined by multivariate Cox's proportional hazard models. Of the 1411 participants, 27% sustained an acute injury and 51% suffered from overuse injury. Concerning acute injuries, highest risk for severe injuries were detected among conscripts with low fitness level in both the standing long-jump and push-up tests (hazard rate, HR=5.9; 95% CI: 1.6‒21.3). A history of good degree in school sports was not a protective factor against acute injuries. High waist circumference and, on the other hand, being underweight according to BMI increased the HR for overuse injuries. Brisk leisure time physical activity before military entry was a protective factor against overuse injuries. Poor result in Cooper's test was a warning signal of elevated risk of overuse injuries. We confirmed previous findings that low level of physical fitness is predictor for musculoskeletal injuries during intensive physical training. The U-shaped relationship between body composition and overuse injuries was noticed indicating that both obesity and underweight are risk factors for overuse injuries. Persons

Apigenin Attenuates Inflammation in Experimentally Induced Acute Pancreatitis-Associated Lung Injury.

PubMed

Basios, Neofitos; Lampropoulos, Pavlos; Papalois, Apostolos; Lambropoulou, Maria; Pitiakoudis, Michael K; Kotini, Athanasia; Simopoulos, Constantinos; Tsaroucha, Alexandra K

2016-06-01

Acute pancreatitis is associated with acute lung injury. The aim of the present study is to evaluate alterations of lungs in an experimental model of acute pancreatitis (AP) following both bilio-pancreatic duct obstruction close to the duodenum. Acute pancreatitis is a common disease with significant mortality. This situation makes the need of finding protective factors for the lung parenchyma, imperative. In the present study there is an effort to clarify the role of apigenin, a substance which is well known for its antioxidant and anti-inflammatory effects, on lung injury, following acute pancreatitis in rats. In the present study, 126 male Wistar-type rats 3-4 months old and 220-350 g weight were used. At time 0 we randomly assigned the following groups: Group Sham: Rats were subjected to virtual surgery. Group Control: Rats were subjected to surgery for induction of acute pancreatitis. Group Apigenin: Rats were subjected to surgery for induction of acute pancreatitis and enteral feeding with apigenin. Immunochemistry for TNF-α and IL-6 as well as MPO activity were measured at predetermined time intervals 6, 12, 24, 48, and 72 h, in order to evaluate architectural disturbances of the lung tissue. From the pathological reports we realized that comparing the control group with the apigenin group, there is an improvement of lung tissue damage following apigenin administration, with statistical significance. Apigenin reduces most histopathological alterations of the pulmonary tissue, reduces MPO and TNF-α activity at 48 hours and, furthermore, reduces IL-6 activity at 72 hours post-administration. Oral Apigenin administration in rats, following experimental induced acute pancreatitis, seems to be protective on the lung tissue. Apigenin administration to humans could potentially ameliorate acute lung injuries. However, special caution is required for humans' use, as more detailed studies are needed.

The Effects of Injury Magnitude on the Kinetics of the Acute Phase Response

PubMed Central

Bauzá, Graciela; Miller, Glenn; Kaseje, Neema; Wigner, Nathan A.; Wang, Zhongyan; Gerstenfeld, Louis C.; Burke, Peter A.

2013-01-01

Background The acute-phase response (APR) is critical to the body's ability to successfully respond to injury. A murine model of closed unilateral femur fractures and bilateral femur fracture were used to study the effect of injury magnitude on this response. Methods Standardized unilateral femur fracture and bilateral femur fracture in mice were performed. The femur fracture sites, livers, and serum were harvested over time after injury. Changes in mRNA expression of cytokines, hepatic acute-phase proteins, and serum cytokines overtime were measured. Results There was a rapid and short-lived hepatic APR to fracture injuries. The overall pattern in both models was similar. Both acute-phase proteins' mRNA (fibrinogen-γ and serum amyloid A-3) showed increased mRNA expression over baseline within the first 48 hours and their levels positively correlated with the extent of injury. However, increased severity of injury resulted in a delayed induction of the APR. A similar effect on the gene expression of cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor-α) at the fracture site was seen. Serum IL-6 levels increased with increased injury and showed no delay between injury models. Conclusions Greater severity of injury resulted in a delayed induction of the liver's APR and a diminished expression of cytokines at the fracture site. Serum IL-6 levels were calibrated to the extent of the injury, and changes may represent mechanisms by which the local organ responses to injury are regulated by the injury magnitude. PMID:20693926

Neuroprotection and Acute Spinal Cord Injury: A Reappraisal

PubMed Central

Hall, Edward D.; Springer, Joe E.

2004-01-01

Summary: It has long been recognized that much of the post-traumatic degeneration of the spinal cord following injury is caused by a multi-factorial secondary injury process that occurs during the first minutes, hours, and days after spinal cord injury (SCI). A key biochemical event in that process is reactive oxygen-induced lipid peroxidation (LP). In 1990 the results of the Second National Acute Spinal Cord Injury Study (NASCIS II) were published, which showed that the administration of a high-dose regimen of the glucocorticoid steroid methylprednisolone (MP), which had been previously shown to inhibit post-traumatic LP in animal models of SCI, could improve neurological recovery in spinal-cord-injured humans. This resulted in the registration of high-dose MP for acute SCI in several countries, although not in the U.S. Nevertheless, this treatment quickly became the standard of care for acute SCI since the drug was already on the U.S. market for many other indications. Subsequently, it was demonstrated that the non-glucocorticoid 21-aminosteroid tirilazad could duplicate the antioxidant neuroprotective efficacy of MP in SCI models, and evidence of human efficacy was obtained in a third NASCIS trial (NASCIS III). In recent years, the use of high-dose MP in acute SCI has become controversial largely on the basis of the risk of serious adverse effects versus what is perceived to be on average a modest neurological benefit. The opiate receptor antagonist naloxone was also tested in NASCIS II based upon the demonstration of its beneficial effects in SCI models. Although it did not a significant overall effect, some evidence of efficacy was seen in incomplete (i.e., paretic) patients. The monosialoganglioside GM1 has also been examined in a recently completed clinical trial in which the patients first received high-dose MP treatment. However, GM1 failed to show any evidence of a significant enhancement in the extent of neurological recovery over the level afforded by

Glutamine's protection against cellular injury is dependent on heat shock factor-1.

PubMed

Morrison, Angela L; Dinges, Martin; Singleton, Kristen D; Odoms, Kelli; Wong, Hector R; Wischmeyer, Paul E

2006-06-01

Glutamine (GLN) has been shown to protect cells, tissues, and whole organisms from stress and injury. Enhanced expression of heat shock protein (HSP) has been hypothesized to be responsible for this protection. To date, there are no clear mechanistic data confirming this relationship. This study tested the hypothesis that GLN-mediated activation of the HSP pathway via heat shock factor-1 (HSF-1) is responsible for cellular protection. Wild-type HSF-1 (HSF-1(+/+)) and knockout (HSF-1(-/-)) mouse fibroblasts were used in all experiments. Cells were treated with GLN concentrations ranging from 0 to 16 mM and exposed to heat stress injury in a concurrent treatment model. Cell viability was assayed with phenazine methosulfate plus tetrazolium salt, HSP-70, HSP-25, and nuclear HSF-1 expression via Western blot analysis, and HSF-1/heat shock element (HSE) binding via EMSA. GLN significantly attenuated heat-stress induced cell death in HSF-1(+/+) cells in a dose-dependent manner; however, the survival benefit of GLN was lost in HSF-1(-/-) cells. GLN led to a dose-dependent increase in HSP-70 and HSP-25 expression after heat stress. No inducible HSP expression was observed in HSF-1(-/-) cells. GLN increased unphosphorylated HSF-1 in the nucleus before heat stress. This was accompanied by a GLN-mediated increase in HSF-1/HSE binding and nuclear content of phosphorylated HSF-1 after heat stress. This is the first demonstration that GLN-mediated cellular protection after heat-stress injury is related to HSF-1 expression and cellular capacity to activate an HSP response. Furthermore, the mechanism of GLN-mediated protection against injury appears to involve an increase in nuclear HSF-1 content before stress and increased HSF-1 promoter binding and phosphorylation.

Demographics of acute admissions to a National Spinal Injuries Unit.

PubMed

Lenehan, B; Boran, S; Street, J; Higgins, T; McCormack, D; Poynton, A R

2009-07-01

This prospective demographic study was undertaken to review the epidemiology and demographics of all acute admissions to the National Spinal Injuries Unit in Ireland for the 5 years to 2003. The study was conducted at the National Spinal Injuries Unit, Mater Miscericordiae University Hospital, Dublin, Ireland. Records of all patients admitted to our unit from 1999 to 2003 were compiled from a prospective computerized spinal database. In this 5-year period, 942 patients were acutely hospitalized at the National Spinal Injuries Unit. There were 686 (73%) males and 256 (27%) females, with an average age of 32 years (range 16-84 years). The leading cause of admission with a spinal injury was road traffic accidents (42%), followed by falls (35%), sport (11%), neoplasia (7.5%) and miscellaneous (4.5%). The cervical spine was most commonly affected (51%), followed by lumbar (28%) and thoracic (21%). On admission 38% of patients were ASIA D or worse, of which one-third were AISA A. Understanding of the demographics of spinal column injuries in unique populations can help us to develop preventative and treatment strategies at both national and international levels.

Risk factors and outcomes of acute kidney injury in patients with acute liver failure.

PubMed

Tujios, Shannan R; Hynan, Linda S; Vazquez, Miguel A; Larson, Anne M; Seremba, Emmanuel; Sanders, Corron M; Lee, William M

2015-02-01

Patients with acute liver failure (ALF) frequently develop renal dysfunction, yet its overall incidence and outcomes have not been fully assessed. We investigated the incidence of acute kidney injury (AKI) among patients with ALF, using defined criteria to identify risk factors and to evaluate its effect on overall outcomes. We performed a retrospective review of data from 1604 patients enrolled in the Acute Liver Failure Study Group, from 1998 through 2010. Patients were classified by the Acute Kidney Injury Network criteria, as well as for etiology of liver failure (acetaminophen-based, ischemic, and all others). Seventy percent of patients with ALF developed AKI, and 30% received renal replacement therapy (RRT). Patients with severe AKI had higher international normalized ratio values than those without renal dysfunction (P < .001), and a higher proportion had advanced-grade coma (coma grades 3 or 4; P < .001) or presented with hypotension requiring vasopressor therapy (P < .001). A greater proportion of patients with acetaminophen-induced ALF had severe kidney injury than of patients with other etiologies of ALF; 34% required RRT, compared with 25% of patients with ALF not associated with acetaminophen or ischemia (P < .002). Of the patients with ALF who were alive at 3 weeks after study entry, significantly fewer with AKI survived for 1 year. Although AKI reduced the overall survival time, more than 50% of patients with acetaminophen-associated or ischemic ALF survived without liver transplantation (even with RRT), compared with 19% of patients with ALF attribute to other causes (P < .001). Only 4% of patients requiring RRT became dependent on dialysis. Based on a retrospective analysis of data from more than 1600 patients, AKI is common in patients with ALF and affects short- and long-term outcomes, but rarely results in chronic kidney disease. Acetaminophen-induced kidney injury is frequent, but patients have better outcomes than those with other forms of

4.7-T diffusion tensor imaging of acute traumatic peripheral nerve injury

PubMed Central

Boyer, Richard B.; Kelm, Nathaniel D.; Riley, D. Colton; Sexton, Kevin W.; Pollins, Alonda C.; Shack, R. Bruce; Dortch, Richard D.; Nanney, Lillian B.; Does, Mark D.; Thayer, Wesley P.

2015-01-01

Diagnosis and management of peripheral nerve injury is complicated by the inability to assess microstructural features of injured nerve fibers via clinical examination and electrophysiology. Diffusion tensor imaging (DTI) has been shown to accurately detect nerve injury and regeneration in crush models of peripheral nerve injury, but no prior studies have been conducted on nerve transection, a surgical emergency that can lead to permanent weakness or paralysis. Acute sciatic nerve injuries were performed microsurgically to produce multiple grades of nerve transection in rats that were harvested 1 hour after surgery. High-resolution diffusion tensor images from ex vivo sciatic nerves were obtained using diffusion-weighted spin-echo acquisitions at 4.7 T. Fractional anisotropy was significantly reduced at the injury sites of transected rats compared with sham rats. Additionally, minor eigenvalues and radial diffusivity were profoundly elevated at all injury sites and were negatively correlated to the degree of injury. Diffusion tensor tractography showed discontinuities at all injury sites and significantly reduced continuous tract counts. These findings demonstrate that high-resolution DTI is a promising tool for acute diagnosis and grading of traumatic peripheral nerve injuries. PMID:26323827

Spinning-induced Rhabdomyolysis and the Risk of Compartment Syndrome and Acute Kidney Injury

PubMed Central

DeFilippis, Ersilia M.; Kleiman, David A.; Derman, Peter B.; DiFelice, Gregory S.; Eachempati, Soumitra R.

2014-01-01

Exercise-induced rhabdomyolysis related to military training, marathon running, and other forms of strenuous exercise has been reported. The incidence of acute kidney injury appears to be lower in exercise-induced cases. We present 2 cases of exercise-induced rhabdomyolysis following spinning classes, one of which was further complicated by acute compartment syndrome requiring bilateral fasciotomies of the anterior thigh and acute kidney injury. With vigorous hydration and urine pH monitoring, both patients exhibited good mobility, sensation, and renal function on discharge. PMID:24982706

Acute transient cognitive dysfunction and acute brain injury induced by systemic inflammation occur by dissociable IL-1-dependent mechanisms.

PubMed

Skelly, Donal T; Griffin, Éadaoin W; Murray, Carol L; Harney, Sarah; O'Boyle, Conor; Hennessy, Edel; Dansereau, Marc-Andre; Nazmi, Arshed; Tortorelli, Lucas; Rawlins, J Nicholas; Bannerman, David M; Cunningham, Colm

2018-06-06

Systemic inflammation can impair cognition with relevance to dementia, delirium and post-operative cognitive dysfunction. Episodes of delirium also contribute to rates of long-term cognitive decline, implying that these acute events induce injury. Whether systemic inflammation-induced acute dysfunction and acute brain injury occur by overlapping or discrete mechanisms remains unexplored. Here we show that systemic inflammation, induced by bacterial LPS, produces both working-memory deficits and acute brain injury in the degenerating brain and that these occur by dissociable IL-1-dependent processes. In normal C57BL/6 mice, LPS (100 µg/kg) did not affect working memory but impaired long-term memory consoliodation. However prior hippocampal synaptic loss left mice selectively vulnerable to LPS-induced working memory deficits. Systemically administered IL-1 receptor antagonist (IL-1RA) was protective against, and systemic IL-1β replicated, these working memory deficits. Dexamethasone abolished systemic cytokine synthesis and was protective against working memory deficits, without blocking brain IL-1β synthesis. Direct application of IL-1β to ex vivo hippocampal slices induced non-synaptic depolarisation and irrevesible loss of membrane potential in CA1 neurons from diseased animals and systemic LPS increased apoptosis in the degenerating brain, in an IL-1RI -/- -dependent fashion. The data suggest that LPS induces working memory dysfunction via circulating IL-1β but direct hippocampal action of IL-1β causes neuronal dysfunction and may drive neuronal death. The data suggest that acute systemic inflammation produces both reversible cognitive deficits, resembling delirium, and acute brain injury contributing to long-term cognitive impairment but that these events are mechanistically dissociable. These data have significant implications for management of cognitive dysfunction during acute illness.

Cyclosporine-assisted adipose-derived mesenchymal stem cell therapy to mitigate acute kidney ischemia–reperfusion injury

PubMed Central

2013-01-01

Introduction This study tested the hypothesis that cyclosporine (CsA)-supported syngeneic adipose-derived mesenchymal stem cell (ADMSC) therapy offered superior attenuation of acute ischemia–reperfusion (IR) kidney injury to either therapy alone. Methods Adult Sprague–Dawley rats (n = 40) were equally divided into group 1 (sham controls), group 2 (IR injury), group 3 (IR + CsA (20 mg/kg at 1 and 24 hours after procedure)), group 4 (syngeneic ADMSC (1.2×106) at 1, 6 and 24 hours after procedure), and group 5 (IR + CsA-ADMSC). Results By 72 hours after the IR procedure, the creatinine level and the ratio of urine protein to creatinine were highest in group 2 and lowest in group 1, and significantly higher in groups 3 and 4 than in group 5 (all P <0.05 for inter-group comparisons), but showed no differences between groups 3 and 4 (P >0.05). The inflammatory biomarkers at mRNA (matrix metalloproteinase-9, RANTES, TNF-α), protein (TNF-α, NF-κB, intercellular adhesion molecule-1, platelet-derived growth factor), and cellular (CD68+) levels of IR kidney showed a similar pattern compared with that of creatinine in all groups (all P <0.05 for inter-group comparisons). The protein expressions of oxidative stress (oxidized protein), reactive oxygen species (NADPH oxidases NOX-1, NOX-2), apoptosis (Bcl-2–associated X protein, caspase-3 and poly(ADP-ribose) polymerase) and DNA damage (phosphorylated H2A histone family member X-positive, proliferating cell nuclear antigen-positive cells) markers exhibited a pattern similar to that of inflammatory mediators amongst all groups (all P <0.05 for inter-group comparisons). Expressions of antioxidant biomarkers at cellular (glutathione peroxidase, glutathione reductase, heme oxygenase-1 (HO-1)) and protein (NADPH dehydrogenase (quinone)-1, HO-1, endothelial nitric oxide synthase) levels, and endothelial progenitor cell markers (C-X-C chemokine receptor type 4-positive, stromal cell-derived factor-1α-positive) were lowest in

Cyclosporine-assisted adipose-derived mesenchymal stem cell therapy to mitigate acute kidney ischemia-reperfusion injury.

PubMed

Chen, Yen-Ta; Yang, Chih-Chau; Zhen, Yen-Yi; Wallace, Christopher Glenn; Yang, Jenq-Lin; Sun, Cheuk-Kwan; Tsai, Tzu-Hsien; Sheu, Jiunn-Jye; Chua, Sarah; Chang, Chia-Lo; Cho, Chung-Lung; Leu, Steve; Yip, Hon-Kan

2013-05-31

This study tested the hypothesis that cyclosporine (CsA)-supported syngeneic adipose-derived mesenchymal stem cell (ADMSC) therapy offered superior attenuation of acute ischemia-reperfusion (IR) kidney injury to either therapy alone. Adult Sprague-Dawley rats (n = 40) were equally divided into group 1 (sham controls), group 2 (IR injury), group 3 (IR + CsA (20 mg/kg at 1 and 24 hours after procedure)), group 4 (syngeneic ADMSC (1.2×106) at 1, 6 and 24 hours after procedure), and group 5 (IR + CsA-ADMSC). By 72 hours after the IR procedure, the creatinine level and the ratio of urine protein to creatinine were highest in group 2 and lowest in group 1, and significantly higher in groups 3 and 4 than in group 5 (all P <0.05 for inter-group comparisons), but showed no differences between groups 3 and 4 (P >0.05). The inflammatory biomarkers at mRNA (matrix metalloproteinase-9, RANTES, TNF-α), protein (TNF-α, NF-κB, intercellular adhesion molecule-1, platelet-derived growth factor), and cellular (CD68+) levels of IR kidney showed a similar pattern compared with that of creatinine in all groups (all P <0.05 for inter-group comparisons). The protein expressions of oxidative stress (oxidized protein), reactive oxygen species (NADPH oxidases NOX-1, NOX-2), apoptosis (Bcl-2-associated X protein, caspase-3 and poly(ADP-ribose) polymerase) and DNA damage (phosphorylated H2A histone family member X-positive, proliferating cell nuclear antigen-positive cells) markers exhibited a pattern similar to that of inflammatory mediators amongst all groups (all P <0.05 for inter-group comparisons). Expressions of antioxidant biomarkers at cellular (glutathione peroxidase, glutathione reductase, heme oxygenase-1 (HO-1)) and protein (NADPH dehydrogenase (quinone)-1, HO-1, endothelial nitric oxide synthase) levels, and endothelial progenitor cell markers (C-X-C chemokine receptor type 4-positive, stromal cell-derived factor-1α-positive) were lowest in groups 1 and 2, higher in groups 3

The outcomes of children with pediatric acute respiratory distress syndrome: proceedings from the Pediatric Acute Lung Injury Consensus Conference.

PubMed

Quasney, Michael W; López-Fernández, Yolanda M; Santschi, Miriam; Watson, R Scott

2015-06-01

To provide additional details and evidence behind the recommendations for outcomes assessment of patients with pediatric acute respiratory distress syndrome from the Pediatric Acute Lung Injury Consensus Conference. Consensus conference of experts in pediatric acute lung injury. A panel of 27 experts met over the course of 2 years to develop a taxonomy to define pediatric acute respiratory distress syndrome and to make recommendations regarding treatment and research priorities. The outcomes subgroup comprised four experts. When published data were lacking, a modified Delphi approach emphasizing strong professional agreement was used. The Pediatric Acute Lung Injury Consensus Conference experts developed and voted on a total of 151 recommendations addressing the topics related to pediatric acute respiratory distress syndrome, seven of which related to outcomes after pediatric acute respiratory distress syndrome. All seven recommendations had strong agreement. Children with acute respiratory distress syndrome continue to have a high mortality, specifically, in relation to certain comorbidities and etiologies related to pediatric acute respiratory distress syndrome. Comorbid conditions, such as an immunocompromised state, increase the risk of mortality even further. Likewise, certain etiologies, such as non-pulmonary sepsis, also place children at a higher risk of mortality. Significant long-term effects were reported in adult survivors of acute respiratory distress syndrome: diminished lung function and exercise tolerance, reduced quality of life, and diminished neurocognitive function. Little knowledge of long-term outcomes exists in children who survive pediatric acute respiratory distress syndrome. Characterization of the longer term consequences of pediatric acute respiratory distress syndrome in children is vital to help identify opportunities for improved therapeutic and rehabilitative strategies that will lessen the long-term burden of pediatric acute

Pathophysiology of Acute Kidney Injury

PubMed Central

Basile, David P.; Anderson, Melissa D.; Sutton, Timothy A.

2014-01-01

Acute kidney injury (AKI) is the leading cause of nephrology consultation and is associated with high mortality rates. The primary causes of AKI include ischemia, hypoxia or nephrotoxicity. An underlying feature is a rapid decline in GFR usually associated with decreases in renal blood flow. Inflammation represents an important additional component of AKI leading to the extension phase of injury, which may be associated with insensitivity to vasodilator therapy. It is suggested that targeting the extension phase represents an area potential of treatment with the greatest possible impact. The underlying basis of renal injury appears to be impaired energetics of the highly metabolically active nephron segments (i.e., proximal tubules and thick ascending limb) in the renal outer medulla, which can trigger conversion from transient hypoxia to intrinsic renal failure. Injury to kidney cells can be lethal or sublethal. Sublethal injury represents an important component in AKI, as it may profoundly influence GFR and renal blood flow. The nature of the recovery response is mediated by the degree to which sublethal cells can restore normal function and promote regeneration. The successful recovery from AKI depends on the degree to which these repair processes ensue and these may be compromised in elderly or CKD patients. Recent data suggest that AKI represents a potential link to CKD in surviving patients. Finally, earlier diagnosis of AKI represents an important area in treating patients with AKI that has spawned increased awareness of the potential that biomarkers of AKI may play in the future. PMID:23798302

An Immunoassay to Rapidly Measure Acetaminophen Protein Adducts Accurately Identifies Patients with Acute Liver Injury or Failure

PubMed Central

Roberts, Dean W.; Lee, William M.; Hinson, Jack A.; Bai, Shasha; Swearingen, Christopher J.; Stravitz, R. Todd; Reuben, Adrian; Letzig, Lynda; Simpson, Pippa M.; Rule, Jody; Fontana, Robert J.; Ganger, Daniel; Reddy, K. Rajender; Liou, Iris; Fix, Oren; James, Laura P.

2017-01-01

Background & Aims A rapid, reliable point-of-care assay to detect acetaminophen protein adducts in serum of patients with acute liver injury could improve diagnosis and management. AcetaSTAT is a competitive immunoassay used to measure acetaminophen protein adducts formed by toxic metabolites in serum samples from patients. We compared the accuracy of AcetaSTAT vs high-pressure liquid chromatography with electrochemical detection (HPLC-EC, a sensitive and specific quantitative analytical assay) to detect acetaminophen protein adducts. Methods We collected serum samples from 19 healthy individuals (no liver injury, no recent acetaminophen use), 29 patients without acetaminophen-associated acute liver injury, and 33 patients with acetaminophen-associated acute liver injury participating in the Acute Liver Failure Study Group registry. Each serum sample was analyzed by AcetaSTAT (reported as test band amplitude) and HPLC-EC (the reference standard). We also collected data on patient age, sex, weight, level of alanine aminotransferase on test day and peak values, concentration of acetaminophen, diagnoses (by site investigator and causality review committee), and outcome after 21 days. Differences between groups were analyzed using Fisher’s Exact for categorical variables and Kruskal-Wallis Test or Rank-Sum test for continuous variables. Results AcetaSTAT discriminated between patients with and without acetaminophen-associated acute liver injury; the median (and range) AcetaSTAT test band amplitude for patients with acetaminophen-associated acute liver injury was 584 (range, 222–1027) vs 3678 (range, 394–8289) for those without (P<.001). AcetaSTAT identified patients with acetaminophen-associated acute liver injury with 100% sensitivity, 86.2% specificity, a positive-predictive value of 89.2%, and a negative-predictive value of 100%. Results from AcetaSTAT were positive in 4 subjects who received a causality review committee diagnosis of non

Acute and Chronic Kidney Injury in a Non-Human Primate Model of Partial-Body Irradiation with Bone Marrow Sparing.

PubMed

Cohen, Eric P; Hankey, Kim G; Bennett, Alexander W; Farese, Ann M; Parker, George A; MacVittie, Thomas J

2017-12-01

The development of medical countermeasures against acute and delayed multi-organ injury requires animal models predictive of the human response to radiation and its treatment. Late chronic injury is a well-known feature of radiation nephropathy, but acute kidney injury has not been reported in an appropriate animal model. We have established a single-fraction partial-body irradiation model with minimal marrow sparing in non-human primates. Subject-based medical management was used including parenteral fluids according to prospective morbidity criteria. We show herein that 10 or 11 Gy exposures caused both acute and chronic kidney injury. Acute and chronic kidney injury appear to be dose-independent between 10 and 11 Gy. Acute kidney injury was identified during the first 50 days postirradiation and appeared to resolve before the occurrence of chronic kidney injury, which was progressively more severe up to 180 days postirradiation, which was the end of the study. These findings show that mitigation of the acute radiation syndrome by medical management will unmask delayed late effects that occur months after partial-body irradiation. They further emphasize that both acute and chronic changes in kidney function must be taken into account in the use and timing of mitigators and medical management for acute radiation syndrome and delayed effects of acute radiation exposure (DEARE).

Acute posterior cruciate ligament injuries: effect of location, severity, and associated injuries on surgical management.

PubMed

Anderson, Mark A; Simeone, F Joseph; Palmer, William E; Chang, Connie Y

2018-06-01

To correlate MRI findings of patients with posterior cruciate ligament (PCL) injury and surgical management. A retrospective search yielded 79 acute PCL injuries (36 ± 16 years old, 21 F, 58 M). Two independent readers graded PCL tear location (proximal, middle, or distal third) and severity (low-grade or high-grade partial/complete) and evaluated injury of other knee structures. When available, operative reports were examined and the performed surgical procedure was compared with injury grade, location, and presence of associated injuries. The most commonly injured knee structures in acute PCL tears were posterolateral corner (58/79, 73%) and anterior cruciate ligament (ACL) (48/79, 61%). Of the 64 patients with treatment information, 31/64 (48%) were managed surgically: 12/31 (39%) had PCL reconstruction, 13/31 (42%) had ACL reconstruction, 10/31 (32%) had posterolateral corner reconstruction, 9/31 (29%) had LCL reconstruction, 8/31 (26%) had meniscectomy, and 8/31 (26%) had fixation of a fracture. Proximal third PCL tear and multiligamentous injury were more commonly associated with surgical management (P < 0.05). Posterolateral and posteromedial corner, ACL, collateral ligament, meniscus, patellar retinaculum, and gastrocnemius muscle injury, and fracture were more likely to result in surgical management (P < 0.05). Patients with high-grade partial/complete PCL tear were more likely to have PCL reconstruction as a portion of surgical management (P < 0.05). Location of PCL tear and presence of other knee injuries were associated with surgical management while high-grade/complete PCL tear grade was associated with PCL reconstruction. MRI reporting of PCL tear location, severity, and of other knee structure injuries is important for guiding clinical management.

Functional Characterization of Cultured Keratinocytes after Acute Cutaneous Burn Injury

PubMed Central

Gauglitz, Gerd G.; Zedler, Siegfried; v. Spiegel, Felix; Fuhr, Jasmin; v. Donnersmarck, Guido Henkel; Faist, Eugen

2012-01-01

Background In addition to forming the epithelial barrier against the outside environment keratinocytes are immunologically active cells. In the treatment of severely burned skin, cryoconserved keratinocyte allografts gain in importance. It has been proposed that these allografts accelerate wound healing also due to the expression of a favourable - keratinocyte-derived - cytokine and growth factor milieu. Methods In this study the morphology and cytokine expression profile of keratinocytes from skin after acute burn injury was compared to non-burned skin. Skin samples were obtained from patients after severe burn injury and healthy controls. Cells were cultured and secretion of selected inflammatory mediators was quantified using Bioplex Immunoassays. Immunohistochemistry was performed to analyse further functional and morphologic parameters. Results Histology revealed increased terminal differentiation of keratinocytes (CK10, CK11) in allografts from non-burned skin compared to a higher portion of proliferative cells (CK5, vimentin) in acute burn injury. Increased levels of IL-1α, IL-2, IL-4, IL-10, IFN-γ and TNFα could be detected in culture media of burn injury skin cultures. Both culture groups contained large amounts of IL-1RA. IL-6 and GM-CSF were increased during the first 15 days of culture of burned skin compared to control skin. Levels of VEGF, FGF-basic, TGF-ß und G-CSF were high in both but not significantly different. Cryoconservation led to a diminished mediator synthesis except for higher levels of intracellular IL-1α and IL-1ß. Conclusion Skin allografts from non-burned skin show a different secretion pattern of keratinocyte-derived cytokines and inflammatory mediators compared to keratinocytes after burn injury. As these secreted molecules exert auto- and paracrine effects and subsequently contribute to healing and barrier restoration after acute burn injury therapies affecting this specific cytokine/growth factor micromilieu could be

The diagnostic and prognostic value of ultrasonography in soccer players with acute hamstring injuries.

PubMed

Petersen, Jesper; Thorborg, Kristian; Nielsen, Michael Bachmann; Skjødt, Thomas; Bolvig, Lars; Bang, Niels; Hölmich, Per

2014-02-01

An injury to the hamstring muscle complex is the most common injury in soccer. Ultrasound of acute hamstring injuries is often used as a clinical tool for diagnosing hamstring injuries and guiding players in when they can return to play. To (1) investigate the characteristic sonographic findings of acute hamstring injuries in soccer players, (2) compare the mean injury severity (time to return to play) in injured players with and without sonographically verified abnormalities, and (3) correlate the length of the injured area and absence from soccer play (time to return to play) to investigate if ultrasonography can be used as a prognostic indicator of time to return to play. Case series; Level of evidence, 4. Players from 50 teams participating in 1 of the top 5 Danish soccer divisions were followed in the period from January to December 2008. Of 67 players with acute hamstring injuries, 51 underwent ultrasonographic examination of the injured thigh and were included in this study. Ultrasonographic examinations were performed 1 to 10 days after injury (mean, 5.2 ± 3.0 days), and sonographic findings were present in 31 of 51 cases (61%). Two thirds of the injuries were to the biceps femoris muscle and one third to the semitendinosus muscle. No total ruptures were documented. The 51 acute hamstring injuries resulted in absence from soccer of a mean 25.4 ± 15.7 days per injury, with no significant difference between players with and without sonographically verified abnormalities (P = .41). No correlation existed between the length of the injured area and injury severity (r = 0.19, P = .29). The biceps femoris is the most commonly injured hamstring muscle detected by ultrasound, and more than half of the injuries are intramuscular. Because neither the presence of sonographic findings nor the size of the findings was correlated with time to return to play in injured soccer players, the prognosis of hamstring injuries should not be guided by these findings alone.

MG53-mediated cell membrane repair protects against acute kidney injury

PubMed Central

Lin, Peihui; Tan, Tao; Wang, Zhen; Chen, Ken; Zhou, Xinyu; Gumpper, Kristyn; Zhu, Hua; Ludwig, Thomas; Mohler, Peter J.; Rovin, Brad; Abraham, William T.; Zeng, Chunyu; Ma, Jianjie

2015-01-01

Injury to the renal proximal tubular epithelium (PTE) represents the underlying consequence of acute kidney injury (AKI) after exposure to various stressors, including nephrotoxins and ischemia/reperfusion (I/R). Although the kidney has the ability to repair itself after mild injury, insufficient repair of PTE cells may trigger inflammatory and fibrotic responses, leading to chronic renal failure. We report that MG53, a member of the TRIM family of proteins, participates in repair of injured PTE cells and protects against the development of AKI. We show that MG53 translocates to acute injury sites on PTE cells and forms a repair patch. Ablation of MG53 leads to defective membrane repair. MG53-deficient mice develop pronounced tubulointerstitial injury and increased susceptibility to I/R-induced AKI compared to wild-type mice. Recombinant human MG53 (rhMG53) protein can target injury sites on PTE cells to facilitate repair after I/R injury or nephrotoxin exposure. Moreover, in animal studies, intravenous delivery of rhMG53 ameliorates cisplatin-induced AKI without affecting the tumor suppressor efficacy of cisplatin. These findings identify MG53 as a vital component of reno-protection, and targeting MG53-mediated repair of PTE cells represents a potential approach to prevention and treatment of AKI. PMID:25787762

Serum CXCL10, CXCL11, CXCL12, and CXCL14 chemokine patterns in patients with acute liver injury.

PubMed

Chalin, Arnaud; Lefevre, Benjamin; Devisme, Christelle; Pronier, Charlotte; Carrière, Virginie; Thibault, Vincent; Amiot, Laurence; Samson, Michel

2018-06-04

The chemokines CXCL10 (interferon ϒ-inducible protein 10 [IP-10]), CXCL11 (Human interferon inducible T cell alpha chemokine [I-TAC]), CXCL12 (stromal cell derived factor 1 [SDF-1]), and CXCL14 (breast and kidney-expressed chemokine [BRAK]) are involved in cell recruitment, migration, activation, and homing in liver diseases and have been shown to be upregulated during acute liver injury in animal models. However, their expression in patients with acute liver injury is unknown. Here, we aimed to provide evidence of the presence of circulating CXCL10, CXCL11, CXCL12, and CXCL14 during human acute liver injury to propose new inflammation biomarkers for acute liver injury. We analyzed the serum concentration of the studied chemokines in healthy donors (n = 36) and patients (n = 163) with acute liver injuries of various etiologies. Serum CXCL10, CXCL11 and CXCL12 levels were elevated in all the studied groups except biliary diseases for CXCL11. CXCL14 was associated with only acute viral infection and vascular etiologies. The strongest correlation was found between the IFN-inducible studied chemokines (CXCL10 and CXCL11) in all patients and more specifically in the acute viral infection group. These data provide evidence for the presence of circulating CXCL10, CXCL11, CXCL12, and CXCL14 during acute liver injury and are consistent with data obtained in animal models. CXCL10, CXCL11 and CXCL12 were the most highly represented and CXCL14 the least represented chemokines. Differential expression patterns were obtained depending on acute liver injury etiology, suggesting the potential use of these chemokines as acute liver injury biomarkers. Copyright © 2018. Published by Elsevier Ltd.

Early magnetic resonance detection of cortical necrosis and acute network injury associated with neonatal and infantile cerebral infarction.

PubMed

Okabe, Tetsuhiko; Aida, Noriko; Niwa, Tetsu; Nozawa, Kumiko; Shibasaki, Jun; Osaka, Hitoshi

2014-05-01

Knowledge of MRI findings in pediatric cerebral infarction is limited. To determine whether cortical necrosis and network injury appear in the acute phase in post-stroke children and to identify anatomical location of acute network injury and the ages at which these phenomena are seen. Images from 12 children (age range: 0-9 years; neonates [<1 month], n=5; infants [1 month-12 months], n=3; others [≥1 year], n=4) with acute middle cerebral artery (MCA) cortical infarction were retrospectively analyzed. Cortical necrosis was defined as hyperintense cortical lesions on T1-weighted imaging that lacked evidence of hemorrhage. Acute network injury was defined as hyperintense lesions on diffusion-weighted imaging that were not in the MCA territory and had fiber connections with the affected cerebral cortex. MRI was performed within the first week after disease onset. Cortical necrosis was only found in three neonates. Acute network injury was seen in the corticospinal tract (CST), thalamus and corpus callosum. Acute network injury along the CST was found in five neonates and one 7-month-old infant. Acute network injury was evident in the thalamus of four neonates and two infants (ages 4 and 7 months) and in the corpus callosum of five neonates and two infants (ages 4 and 7 months). The entire thalamus was involved in three children when infarction of MCA was complete. In acute MCA cortical infarction, MRI findings indicating cortical necrosis or acute network injury was frequently found in neonates and early infants. Response to injury in a developing brain may be faster than that in a mature one.

Monitoring inflammation (including fever) in acute brain injury.

PubMed

Provencio, J Javier; Badjatia, Neeraj

2014-12-01

Inflammation is an important part of the normal physiologic response to acute brain injury (ABI). How inflammation is manifest determines if it augments or hinders the resolution of ABI. Monitoring body temperature, the cellular arm of the inflammatory cascade, and inflammatory proteins may help guide therapy. This summary will address the utility of inflammation monitoring in brain-injured adults. An electronic literature search was conducted for English language articles describing the testing, utility, and optimal methods to measure inflammation in ABI. Ninety-four articles were included in this review. Current evidence suggests that control of inflammation after ABI may hold promise for advances in good outcomes. However, our understanding of how much inflammation is good and how much is deleterious is not yet clear. Several important concepts emerge form our review. First, while continuous temperature monitoring of core body temperature is recommended, temperature pattern alone is not useful in distinguishing infectious from noninfectious fever. Second, when targeted temperature management is used, shivering should be monitored at least hourly. Finally, white blood cell levels and protein markers of inflammation may have a limited role in distinguishing infectious from noninfectious fever. Our understanding of optimal use of inflammation monitoring after ABI is limited currently but is an area of active investigation.

A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries

NASA Astrophysics Data System (ADS)

Mann, Aman P.; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Kwon, Ester; Braun, Gary B.; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Bhatia, Sangeeta; Sailor, Michael J.; Ruoslahti, Erkki

2016-06-01

Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries.

Understanding acute ankle ligamentous sprain injury in sports

PubMed Central

Fong, Daniel TP; Chan, Yue-Yan; Mok, Kam-Ming; Yung, Patrick SH; Chan, Kai-Ming

2009-01-01

This paper summarizes the current understanding on acute ankle sprain injury, which is the most common acute sport trauma, accounting for about 14% of all sport-related injuries. Among, 80% are ligamentous sprains caused by explosive inversion or supination. The injury motion often happens at the subtalar joint and tears the anterior talofibular ligament (ATFL) which possesses the lowest ultimate load among the lateral ligaments at the ankle. For extrinsic risk factors to ankle sprain injury, prescribing orthosis decreases the risk while increased exercise intensity in soccer raises the risk. For intrinsic factors, a foot size with increased width, an increased ankle eversion to inversion strength, plantarflexion strength and ratio between dorsiflexion and plantarflexion strength, and limb dominance could increase the ankle sprain injury risk. Players with a previous sprain history, players wearing shoes with air cells, players who do not stretch before exercising, players with inferior single leg balance, and overweight players are 4.9, 4.3, 2.6, 2.4 and 3.9 times more likely to sustain an ankle sprain injury. The aetiology of most ankle sprain injuries is incorrect foot positioning at landing – a medially-deviated vertical ground reaction force causes an explosive supination or inversion moment at the subtalar joint in a short time (about 50 ms). Another aetiology is the delayed reaction time of the peroneal muscles at the lateral aspect of the ankle (60–90 ms). The failure supination or inversion torque is about 41–45 Nm to cause ligamentous rupture in simulated spraining tests on cadaver. A previous case report revealed that the ankle joint reached 48 degrees inversion and 10 degrees internal rotation during an accidental grade I ankle ligamentous sprain injury during a dynamic cutting trial in laboratory. Diagnosis techniques and grading systems vary, but the management of ankle ligamentous sprain injury is mainly conservative. Immobilization should not

Stem Cell Mobilizers: Novel Therapeutics for Acute Kidney Injury.

PubMed

Xu, Yue; Zeng, Song; Zhang, Qiang; Zhang, Zijian; Hu, Xiaopeng

2017-01-01

In the past decade, rapid developments in stem cell studies have occurred. Researchers have confirmed the plasticity of bone marrow stem cells and the repair and regeneration effects of bone marrow hematopoietic stem cells on solid organs. These findings have suggested the possibility of using bone marrow stem cell mobilizers to repair and regenerate injured organs. Recent studies on the effects of granulocyte colony-stimulating factor (G-CSF) and Plerixafor (AMD3100) on mouse acute kidney injury models have confirmed that the use of bone marrow stem cell mobilizers may be an effective therapeutic measure. This paper summarizes studies describing the effects of G-CSF and AMD3100 on various acute kidney injury models over the past 10 years. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Pathophysiology of pulmonary hypertension in acute lung injury

PubMed Central

Price, Laura C.; McAuley, Danny F.; Marino, Philip S.; Finney, Simon J.; Griffiths, Mark J.

2012-01-01

Acute lung injury (ALI) and acute respiratory distress syndrome are characterized by protein rich alveolar edema, reduced lung compliance, and acute severe hypoxemia. A degree of pulmonary hypertension (PH) is also characteristic, higher levels of which are associated with increased morbidity and mortality. The increase in right ventricular (RV) afterload causes RV dysfunction and failure in some patients, with associated adverse effects on oxygen delivery. Although the introduction of lung protective ventilation strategies has probably reduced the severity of PH in ALI, a recent invasive hemodynamic analysis suggests that even in the modern era, its presence remains clinically important. We therefore sought to summarize current knowledge of the pathophysiology of PH in ALI. PMID:22246001

The acute:chonic workload ratio in relation to injury risk in professional soccer.

PubMed

Malone, Shane; Owen, Adam; Newton, Matt; Mendes, Bruno; Collins, Kieran D; Gabbett, Tim J

2017-06-01

To examine the association between combined sRPE measures and injury risk in elite professional soccer. Observational cohort study. Forty-eight professional soccer players (mean±SD age of 25.3±3.1 yr) from two elite European teams were involved within a one season study. Players completed a test of intermittent-aerobic capacity (Yo-YoIR1) to assess player's injury risk in relation to intermittent aerobic capacity. Weekly workload measures and time loss injuries were recorded during the entire period. Rolling weekly sums and week-to-week changes in workload were measured, allowing for the calculation of the acute:chronic workload ratio, which was calculated by dividing the acute (1-weekly) and chronic (4-weekly) workloads. All derived workload measures were modelled against injury data using logistic regression. Odds ratios (OR) were reported against a reference group. Players who exerted pre-season 1-weekly loads of ≥1500 to ≤2120AU were at significantly higher risk of injury compared to the reference group of ≤1500AU (OR=1.95, p=0.006). Players with increased intermittent-aerobic capacity were better able to tolerate increased 1-weekly absolute changes in training load than players with lower fitness levels (OR=4.52, p=0.011). Players who exerted in-season acute:chronic workload ratios of >1.00 to <1.25 (OR=0.68, p=0.006) were at significantly lower risk of injury compared to the reference group (≤0.85). These findings demonstrate that an acute:chronic workload of between 1.00 and 1.25 is protective for professional soccer players. A higher intermittent-aerobic capacity appears to offer greater injury protection when players are exposed to rapid changes in workload in elite soccer players. Moderate workloads, coupled with moderate-low to moderate-high acute:chronic workload ratios, appear to be protective for professional soccer players. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Application of the Ottawa Knee Rules in assessing acute knee injuries.

PubMed

O'Sullivan, M J A; O'Sullivan, I

2006-01-01

The Ottawa Knee Rules (OKR) were established to identify which adults with acute knee injuries require knee x-rays as part of their assessment. This study evaluates the compliance of non-consultant hospital doctors (NCHDs), working in an Irish Emergency Dept., with these guidelines and assesses the impact of raising the profile of these rules on their implementation. Emergency Dept. (ED) notes of all adults who presented with an acute knee injury in a 3-month period were analysed retrospectively and compliance with the OKR was assessed. ED NCHDs were then educated on the details and value of these guidelines. In the subsequent three months, the improvement in compliance with the OKR was audited. In the initial audit, according to the Ottawa criteria, 65.5% of all x-rays of acute knee injuries were performed unnecessarily. In the second audit, performed after increasing awareness of the OKR, this figure had dropped to 39.1%. The NCHDs involved in this project cited 'patient expectation' for an x-ray as the primary reason why full compliance was not achieved. This study highlights a lack of awareness of and compliance with the OKR in the assessment of acute knee injuries in adults. It shows how the implementation of simple measures, which raised the profile of the OKR among ED staff, significantly improved compliance with the rules, thus cutting patient waiting times and cutting hospital costs. Futhermore, this study revealed that patients, when injured, expect to get x-rayed and ofter doctors comply with these expectations even if no indication exists.

Xenon Protects Against Septic Acute Kidney Injury via miR-21 Target Signaling Pathway.

PubMed

Jia, Ping; Teng, Jie; Zou, Jianzhou; Fang, Yi; Wu, Xie; Liang, Mingyu; Ding, Xiaoqiang

2015-07-01

Septic acute kidney injury is one of the most common and life-threatening complications in critically ill patients, and there is no approved effective treatment. We have shown xenon provides renoprotection against ischemia-reperfusion injury and nephrotoxicity in rodents via inhibiting apoptosis. Here, we studied the effects of xenon preconditioning on septic acute kidney injury and its mechanism. Experimental animal investigation. University research laboratory. Experiments were performed with male C57BL/6 mice, 10 weeks of age, weighing 20-25 g. We induced septic acute kidney injury by a single intraperitoneal injection of Escherichia coli lipopolysaccharide at a dose of 20 mg/kg. Mice were exposed for 2 hours to either 70% xenon or 70% nitrogen, 24 hours before the onset of septic acute kidney injury. In vivo knockdown of miR-21 was performed using locked nucleic acid-modified anti-miR, the role of miR-21 in renal protection conferred by the xenon preconditioning was examined, and miR-21 signaling pathways were analyzed. Xenon preconditioning provided morphologic and functional renoprotection, characterized by attenuation of renal tubular damage, apoptosis, and a reduction in inflammation. Furthermore, xenon treatment significantly upregulated the expression of miR-21 in kidney, suppressed proinflammatory factor programmed cell death protein 4 expression and nuclear factor-κB activity, and increased interleukin-10 production. Meanwhile, xenon preconditioning also suppressed the expression of proapoptotic protein phosphatase and tensin homolog deleted on chromosome 10, activating protein kinase B signaling pathway, subsequently increasing the expression of antiapoptotic B-cell lymphoma-2, and inhibiting caspase-3 activity. Knockdown of miR-21 upregulated its target effectors programmed cell death protein 4 and phosphatase and tensin homolog deleted on chromosome 10 expression, resulted in an increase in apoptosis, and exacerbated lipopolysaccharide

Xenon Protects Against Septic Acute Kidney Injury via miR-21 Target Signaling Pathway*

PubMed Central

Jia, Ping; Teng, Jie; Zou, Jianzhou; Fang, Yi; Wu, Xie; Liang, Mingyu

2015-01-01

Objectives: Septic acute kidney injury is one of the most common and life-threatening complications in critically ill patients, and there is no approved effective treatment. We have shown xenon provides renoprotection against ischemia-reperfusion injury and nephrotoxicity in rodents via inhibiting apoptosis. Here, we studied the effects of xenon preconditioning on septic acute kidney injury and its mechanism. Design: Experimental animal investigation. Setting: University research laboratory. Subjects: Experiments were performed with male C57BL/6 mice, 10 weeks of age, weighing 20–25 g. Interventions: We induced septic acute kidney injury by a single intraperitoneal injection of Escherichia coli lipopolysaccharide at a dose of 20 mg/kg. Mice were exposed for 2 hours to either 70% xenon or 70% nitrogen, 24 hours before the onset of septic acute kidney injury. In vivo knockdown of miR-21 was performed using locked nucleic acid-modified anti-miR, the role of miR-21 in renal protection conferred by the xenon preconditioning was examined, and miR-21 signaling pathways were analyzed. Measurements and Main Results: Xenon preconditioning provided morphologic and functional renoprotection, characterized by attenuation of renal tubular damage, apoptosis, and a reduction in inflammation. Furthermore, xenon treatment significantly upregulated the expression of miR-21 in kidney, suppressed proinflammatory factor programmed cell death protein 4 expression and nuclear factor-κB activity, and increased interleukin-10 production. Meanwhile, xenon preconditioning also suppressed the expression of proapoptotic protein phosphatase and tensin homolog deleted on chromosome 10, activating protein kinase B signaling pathway, subsequently increasing the expression of antiapoptotic B-cell lymphoma-2, and inhibiting caspase-3 activity. Knockdown of miR-21 upregulated its target effectors programmed cell death protein 4 and phosphatase and tensin homolog deleted on chromosome 10

Renal Histopathologic Findings Associated With Severity of Clinical Acute Kidney Injury.

PubMed

Kudose, Satoru; Hoshi, Masato; Jain, Sanjay; Gaut, Joseph P

2018-05-01

Acute kidney injury (AKI) is a significant cause of morbidity and mortality. Acute tubular injury is considered to be the early pathologic manifestation of AKI, however, the underlying pathology is complex, lacks standards for interpretation, and its relationship with AKI often is unclear or inconsistent. To clarify clinicopathologic correlations in AKI, we evaluated 32 histologic findings in 100 kidney biopsies from patients with AKI as a training set to correlate pathologic findings with clinical AKI grades. Kidney Injury Molecule-1 quantitative immunohistochemistry was performed to confirm tubular injury. A separate cohort of 50 biopsies were evaluated blinded to clinical information to validate the findings. Pathologic tubular injury correlated best with Kidney Disease Improving Global Outcomes criteria. Tubular epithelial simplification, tubular epithelial mitosis, and cell sloughing correlated well with clinically severe AKI and were used to construct a tubular injury classification scheme with sensitivity of 0.93 (0.85, 1), specificity of 0.95 (0.83, 1), and area under the receiver-operating characteristic curve of 0.98 (0.98, 1) for grades 2 to 3 AKI. Predictive ability of the model did not improve when Kidney Injury Molecule-1 immunostaining results were added. The results show a strong correlation between pathologic tubular injury and modern clinical definitions of AKI. The proposed classification scheme may aid in development of more precise and clinically meaningful interpretations of pathologic tubular injury in native kidney biopsies and provides simple pathologic criteria without special studies that can easily be adopted globally.

The role of the uncertainty of measurement of serum creatinine concentrations in the diagnosis of acute kidney injury.

PubMed

Kin Tekce, Buket; Tekce, Hikmet; Aktas, Gulali; Uyeturk, Ugur

2016-01-01

Uncertainty of measurement is the numeric expression of the errors associated with all measurements taken in clinical laboratories. Serum creatinine concentration is the most common diagnostic marker for acute kidney injury. The goal of this study was to determine the effect of the uncertainty of measurement of serum creatinine concentrations on the diagnosis of acute kidney injury. We calculated the uncertainty of measurement of serum creatinine according to the Nordtest Guide. Retrospectively, we identified 289 patients who were evaluated for acute kidney injury. Of the total patient pool, 233 were diagnosed with acute kidney injury using the AKIN classification scheme and then were compared using statistical analysis. We determined nine probabilities of the uncertainty of measurement of serum creatinine concentrations. There was a statistically significant difference in the number of patients diagnosed with acute kidney injury when uncertainty of measurement was taken into consideration (first probability compared to the fifth p = 0.023 and first probability compared to the ninth p = 0.012). We found that the uncertainty of measurement for serum creatinine concentrations was an important factor for correctly diagnosing acute kidney injury. In addition, based on the AKIN classification scheme, minimizing the total allowable error levels for serum creatinine concentrations is necessary for the accurate diagnosis of acute kidney injury by clinicians.

Connecting the dots: an association between opioids and acute hippocampal injury.

PubMed

Barash, Jed A; Kofke, W Andrew

2018-04-01

Acute hippocampal injury represents a relatively rare cause of amnesia. Interestingly however, between 2012 and 2017, 18 patients were reported at hospitals in Massachusetts with sudden-onset amnesia in the setting of complete diffusion-weighted hyperintensity of both hippocampi on magnetic resonance imaging. Notably, 17 of the 18 patients tested positive for opioids or had a recorded history of opioid use. This observation suggests an association between opioids and acute hippocampal injury. With particular attention to the Massachusetts cluster and data on fentanyl and its congeners, the epidemiological and pathophysiological evidence that supports this hypothesis is presented, as are potential underlying mechanisms.

Contrast-Induced Acute Kidney Injury: Comparison of Preventative Therapies.

PubMed

Honicker, Theresa; Holt, Karyn

2016-01-01

Contrast medium is used daily for diagnostic and interventional procdures as a means to visualize blood vessels. The administration of contrast dye, however, can lead to an acute reduction in kidney function. This complication can impact length of hospital stay, risk of dialysis, and increased hospital mortality. Common preventative measures include N-acetylcysteine and intravenous hydration. The evidence reviewed revealed hydration to be the more effective treatment to reduce the risk of acute kidney injury.

Pediatric thermal injury: acute care and reconstruction update.

PubMed

Armour, Alexis D; Billmire, David A

2009-07-01

The acute and reconstructive care of each pediatric burn patient presents unique challenges to the plastic surgeon and the burn care team. : The purpose of this review article is to highlight the interdependence between the acute and reconstructive needs of pediatric burn patients as it pertains to each anatomical site. Relevant principles of acute pediatric burn care and burn reconstruction are outlined, based on the authors' experience and review of the literature. The need for late reconstruction in pediatric burn survivors is significantly influenced by the acute surgical and rehabilitative treatments. With their vulnerability to airway swelling, hypothermia, pulmonary edema, and ischemia-reperfusion injury, pediatric patients with large burns require precise, life-saving treatment in the acute phase. Decision-making in pediatric burn reconstruction must take into account the patient's future growth, maturity, and often lack of suitable donor sites. Appropriately selected reconstructive techniques are essential to optimize function, appearance, and quality of life in pediatric burn survivors.

The role of high airway pressure and dynamic strain on ventilator-induced lung injury in a heterogeneous acute lung injury model.

PubMed

Jain, Sumeet V; Kollisch-Singule, Michaela; Satalin, Joshua; Searles, Quinn; Dombert, Luke; Abdel-Razek, Osama; Yepuri, Natesh; Leonard, Antony; Gruessner, Angelika; Andrews, Penny; Fazal, Fabeha; Meng, Qinghe; Wang, Guirong; Gatto, Louis A; Habashi, Nader M; Nieman, Gary F

2017-12-01

Acute respiratory distress syndrome causes a heterogeneous lung injury with normal and acutely injured lung tissue in the same lung. Improperly adjusted mechanical ventilation can exacerbate ARDS causing a secondary ventilator-induced lung injury (VILI). We hypothesized that a peak airway pressure of 40 cmH 2 O (static strain) alone would not cause additional injury in either the normal or acutely injured lung tissue unless combined with high tidal volume (dynamic strain). Pigs were anesthetized, and heterogeneous acute lung injury (ALI) was created by Tween instillation via a bronchoscope to both diaphragmatic lung lobes. Tissue in all other lobes was normal. Airway pressure release ventilation was used to precisely regulate time and pressure at both inspiration and expiration. Animals were separated into two groups: (1) over-distension + high dynamic strain (OD + H DS , n = 6) and (2) over-distension + low dynamic strain (OD + L DS , n = 6). OD was caused by setting the inspiratory pressure at 40 cmH 2 O and dynamic strain was modified by changing the expiratory duration, which varied the tidal volume. Animals were ventilated for 6 h recording hemodynamics, lung function, and inflammatory mediators followed by an extensive necropsy. In normal tissue (N T ), OD + L DS caused minimal histologic damage and a significant reduction in BALF total protein (p < 0.05) and MMP-9 activity (p < 0.05), as compared with OD + H DS . In acutely injured tissue (ALI T ), OD + L DS resulted in reduced histologic injury and pulmonary edema (p < 0.05), as compared with OD + H DS . Both N T and ALI T are resistant to VILI caused by OD alone, but when combined with a H DS , significant tissue injury develops.

Acute kidney injury and cardiovascular outcomes in acute severe hypertension.

PubMed

Szczech, Lynda A; Granger, Christopher B; Dasta, Joseph F; Amin, Alpesh; Peacock, W Frank; McCullough, Peter A; Devlin, John W; Weir, Matthew R; Katz, Jason N; Anderson, Frederick A; Wyman, Allison; Varon, Joseph

2010-05-25

Little is known about the association of kidney dysfunction and outcome in acute severe hypertension. This study aimed to measure the association between baseline chronic kidney disease (estimated glomerular filtration rate), acute kidney injury (AKI, decrease in estimated glomerular filtration rate > or =25% from baseline) and outcome in patients hospitalized with acute severe hypertension. The Studying the Treatment of Acute Hypertension (STAT) registry enrolled patients with acute severe hypertension, defined as > or =1 blood pressure measurement >180 mm Hg systolic and/or >110 mm Hg diastolic and treated with intravenous antihypertensive therapy. Data were compared across groups categorized by admission estimated glomerular filtration rate and AKI during admission. On admission, 79% of the cohort (n=1566) had at least mild chronic kidney disease (estimated glomerular filtration rate <60 mL/min in 46%, <30 mL/min in 22%). Chronic kidney disease patients were more likely to develop heart failure (P<0.0001), non-ST-elevation myocardial infarction (P=0.003), and AKI (P<0.007). AKI patients were at greater risk of heart failure and cardiac arrest (P< or =0.0001 for both). Subjects with AKI experienced higher mortality at 90 days (P=0.003). Any acute loss of estimated glomerular filtration rate during hospitalization was independently associated with an increased risk of death (odds ratio, 1.05; P=0.03 per 10-mL/min decline). Other independent predictors of mortality included increasing age (P<0.0001), male gender (P=0.016), white versus black race (P=0.003), and worse baseline kidney function (P=0.003). Chronic kidney disease is a common comorbidity among patients admitted with acute severe hypertension, and AKI is a frequent form of acute target organ dysfunction, particularly in those with baseline chronic kidney disease. Any degree of AKI is associated with a greater risk of morbidity and mortality.

Acute Kidney Injury in Patients with Cirrhosis

PubMed Central

Russ, Kirk B.; Stevens, Todd M; Singal, Ashwani K.

2015-01-01

Acute kidney injury (AKI) occurs commonly in patients with advanced cirrhosis and negatively impacts pre- and post-transplant outcomes. Physiologic changes that occur in patients with decompensated cirrhosis with ascites, place these patients at high risk of AKI. The most common causes of AKI in cirrhosis include prerenal injury, acute tubular necrosis (ATN), and the hepatorenal syndrome (HRS), accounting for more than 80% of AKI in this population. Distinguishing between these causes is particularly important for prognostication and treatment. Treatment of Type 1 HRS with vasoconstrictors and albumin improves short term survival and renal function in some patients while awaiting liver transplantation. Patients with HRS who fail to respond to medical therapy or those with severe renal failure of other etiology may require renal replacement therapy. Simultaneous liver kidney transplant (SLK) is needed in many of these patients to improve their post-transplant outcomes. However, the criteria to select patients who would benefit from SLK transplantation are based on consensus and lack strong evidence to support them. In this regard, novel serum and/or urinary biomarkers such as neutrophil gelatinase-associated lipocalin, interleukins-6 and 18, kidney injury molecule-1, fatty acid binding protein, and endothelin-1 are emerging with a potential for accurately differentiating common causes of AKI. Prospective studies are needed on the use of these biomarkers to predict accurately renal function recovery after liver transplantation alone in order to optimize personalized use of SLK. PMID:26623266

Pulmonary function test findings in patients with acute inhalation injury caused by smoke bombs

PubMed Central

Cao, Lu; Zhang, Xin-Gang; Wang, Jian-Guo; Wang, Han-Bin; Chen, Yi-Bing; Zhao, Da-Hui; Shi, Wen-Fang

2016-01-01

Background This study aimed to determine the effects of smoke bomb-induced acute inhalation injury on pulmonary function at different stages of lung injury. Methods We performed pulmonary function tests (PFTs) in 15 patients with acute inhalation injury from days 3 to 180 after smoke inhalation. We measured the trace element zinc in whole blood on days 4 and 17, and correlations of zinc levels with PFTs were performed. Results In the acute stage of lung injury (day 3), 3 of 11 patients with mild symptoms had normal pulmonary function and 8 patients with restrictive ventilatory dysfunction and reduced diffusing capacity. Some patients also had mild obstructive ventilatory dysfunction (5 patients) and a decline in small airway function (6 patients). For patients with severe symptoms, PFT results showed moderate to severe restrictive ventilatory dysfunction and reduced diffusing capacity. PaCO2 was significantly higher (P=0.047) in patients with reduced small airway function compared with those with normal small airway function. Whole blood zinc levels in the convalescence stage (day 17) were significantly lower than those in the acute stage (day 4). Zinc in the acute stage was negatively correlated with DLCO/VA on days 3, 10, and 46 (r=−0.633, −0.676, and −0.675 respectively, P<0.05). Conclusions Smoke inhalation injury mainly causes restrictive ventilatory dysfunction and reduced diffusing capacity, and causes mild obstructive ventilatory dysfunction and small airway function decline in some patients. Zinc is negatively correlated with DLCO/VA. Zinc levels may be able to predict prognosis and indicate the degree of lung injury. PMID:28066595

Stressful life events and acute kidney injury in intensive and semi-intensive care unities.

PubMed

Diniz, Denise Para; Marques, Daniella Aparecida; Blay, Sérgio Luis; Schor, Nestor

2012-03-01

Several studies point out that pathophysiological changes related to stress may influence renal function and are associated with disease onset and evolution. However, we have not found any studies about the influence of stress on renal function and acute kidney injury. To evaluate the association between stressful life events and acute kidney injury diagnosis, specifying the most stressful classes of events for these patients in the past 12 months. Case-control study. The study was carried out at Hospital São Paulo, in Universidade Federal de São Paulo and at Hospital dos Servidores do Estado de São Paulo, in Brazil. Patients with acute kidney injury and no chronic disease, admitted to the intensive or semi-intensive care units were included. Controls included patients in the same intensive care units with other acute diseases, except for the acute kidney injury, and also with no chronic disease. Out of the 579 patients initially identified, 475 answered to the Social Readjustment Rating Scale (SRRS) questionnaire and 398 were paired by age and gender (199 cases and 199 controls). The rate of stressful life events was statistically similar between cases and controls. The logistic regression analysis to detect associated effects of the independent variables to the stressful events showed that: increasing age and economic classes A and B in one of the hospitals (Hospital São Paulo - UNIFESP) increased the chance of a stressful life event (SLE). This study did not show association between the Acute Kidney Injury Group with a higher frequency of stressful life events, but that old age, higher income, and type of clinical center were associated.

Lung lavage with oxygenated perfluorochemical liquid in acute lung injury.

PubMed

Richman, P S; Wolfson, M R; Shaffer, T H

1993-05-01

To investigate the effects of lung lavage with oxygenated liquid perfluorochemical on gas exchange, lung mechanics, and cardiac function in animals with acute lung injury. Prospective, randomized, controlled trial. Animal laboratory. Eight adult cats (2 to 4 kg, random sex). Two insults were combined to cause lung injury: oleic acid infusion and saline whole-lung wash. Animals were assigned to either the control or treatment group which consisted of a perfluorochemical liquid (Rimar 101) lavage. Perfluorochemical liquid lavage was performed three times at hourly intervals after lung injury. Three other cats with identical injury but no perfluorochemical liquid lavage served as control animals. All cats were ventilated with an FIO2 of 0.95 and positive end-expiratory pressure of 2 cm H2O continuously. Arterial blood gas tensions and pH, dynamic pulmonary compliance were measured at 15-min intervals. Cardiac index was assessed hourly, and lung fluid was collected after each of the three perfluorochemical liquid lavages. Arterial oxygen tension and pulmonary compliance deteriorated abruptly after lung injury in all cats, and improved significantly (p < .001, two-way analysis of variance) 15 mins after perfluorochemical liquid lavage. These parameters gradually returned to their baseline over 60 mins. Arterial blood pressure and cardiac index decreased after injury in all cats, and were not significantly changed after perfluorochemical liquid lavage. Hemorrhagic fluid was recovered from distal airways by perfluorochemical liquid lavage, despite prior suctioning of the airway. Perfluorochemical liquid lavage removes pulmonary edema fluid and improves gas exchange and the mechanical properties of the lung, after acute severe lung injury.

'Biologic memory' in response to acute kidney injury: cytoresistance, toll-like receptor hyper-responsiveness and the onset of progressive renal disease.

PubMed

Zager, Richard A

2013-08-01

Following the induction of ischemic or toxin-mediated acute kidney injury (AKI), cellular adaptations occur that 're-program' how the kidney responds to future superimposed insults. This re-programming is not simply a short-lived phenomenon; rather it can persist for many weeks, implying that a state of 'biologic memory' has emerged. These changes can be both adaptive and maladaptive in nature and they can co-exist in time. A beneficial adaptation is the emergence of acquired cytoresistance, whereby a number of physiologic responses develop that serve to protect the kidney against further ischemic or nephrotoxic attack. Conversely, some changes are maladaptive, such as a predisposition to Gram-negative or Gram-positive bacteremia due to a renal tubular up-regulation of toll-like receptor responses. This latter change culminates in exaggerated cytokine production, and with efflux into the systemic circulation, extra-renal tissue injury can result (so-called 'organ cross talk'). Another maladaptive response is a persistent up-regulation of pro-inflammatory, pro-fibrotic and vasoconstrictive genes, culminating in progressive renal injury and ultimately end-stage renal failure. The mechanisms by which this biologic re-programming, or biologic memory, is imparted remain subjects for considerable debate. However, injury-induced, and stable, epigenetic remodeling at pro-inflammatory/pro-fibrotic genes seems likely to be involved. The goal of this editorial is to highlight that the so-called 'maintenance phase' of acute renal failure is not a static one, somewhere between injury induction and the onset of repair. Rather, this period is one in which the induction of 'biologic memory' can ultimately impact renal functional recovery, extra-renal injury and the possible transition of AKI into chronic, progressive renal disease.

Cellular injury evidenced by impedance technology and infrared microspectroscopy

NASA Astrophysics Data System (ADS)

le Roux, K.; Prinsloo, L. C.; Meyer, D.

2015-03-01

Fourier Transform Infrared (FTIR) spectroscopy is finding increasing biological application, for example in the analysis of diseased tissues and cells, cell cycle studies and investigating the mechanisms of action of anticancer drugs. Cancer treatment studies routinely define the types of cell-drug responses as either total cell destruction by the drug (all cells die), moderate damage (cell deterioration where some cells survive) or reversible cell cycle arrest (cytostasis). In this study the loss of viability and related chemical stress experienced by cells treated with the medicinal plant, Plectranthus ciliatus, was investigated using real time cell electronic sensing (RT-CES) technology and FTIR microspectroscopy. The use of plants as medicines is well established and ethnobotany has proven that crude extracts can serve as treatments against various ailments. The aim of this study was to determine whether FTIR microspectroscopy would successfully distinguish between different types of cellular injury induced by a potentially anticancerous plant extract. Cervical adenocarcinoma (HeLa) cells were treated with a crude extract of Pciliatus and cells monitored using RT-CES to characterize the type of cellular responses induced. Cell populations were then investigated using FTIR microspectroscopy and statistically analysed using One-way Analysis of Variance (ANOVA) and Principal Component Analysis (PCA). The plant extract and a cancer drug control (actinomycin D) induced concentration dependent cellular responses ranging from nontoxic, cytostatic or cytotoxic. Thirteen spectral peaks (915 cm-1, 933 cm-1, 989 cm-1, 1192 cm-1, 1369 cm-1, 1437 cm-1, 1450 cm-1, 1546 cm-1, 1634 cm-1, 1679 cm-1 1772 cm-1, 2874 cm-1 and 2962 cm-1) associated with cytotoxicity were significantly (p value < 0.05, one way ANOVA, Tukey test, Bonferroni) altered, while two of the bands were also indicative of early stress related responses. In PCA, poor separation between nontoxic and cytostatic

Nonselective inhibition of prostaglandin-endoperoxide synthase by naproxen ameliorates hepatic injury in animals with acute or chronic liver injury

PubMed Central

Bahde, Ralf; Kapoor, Sorabh; Gupta, Sanjeev

2014-01-01

The rising prevalence of hepatic injury due to toxins, metabolites, viruses, etc., necessitates development of further mechanisms for protecting the liver and for treating acute or chronic liver diseases. To examine whether inhibition of inflammation directed by cyclo-oxygenase pathways, we performed animal studies with naproxen, which inhibits prostaglandin-endoperoxide synthases 1 and 2 and is in extensive clinical use. We administered carbon tetrachloride to induce acute liver injury and ligated the common bile duct to induce chronic liver injury in adult rats. These experimental manipulations produced abnormalities in liver tests, tissue necrosis, compensatory hepatocyte or biliary proliferation, and onset of fibrosis, particularly after bile duct ligation. After carbon tetrachloride-induced acute injury, naproxen decreased liver test abnormalities, tissue necrosis and compensatory hepatocellular proliferation. After bile duct ligation-induced chronic injury, naproxen decreased liver test abnormalities, tissue injury and compensatory biliary hyperplasia. Moreover, after bile duct ligation, naproxen-treated rats showed more periductular oval liver cells, which have been classified as hepatic progenitor cells. In naproxen-treated rats, we found greater expression in hepatic stellate cells and mononuclear cells of cytoprotective factors, such as vascular endothelial growth factor. The ability of naproxen to induce expression of vascular endothelial growth factor was verified in cell culture studies with CFSC-8B clone of rat hepatic stellate cells. Whereas assays for carbon tetrachloride toxicity using cultured primary hepatocytes established that naproxen was not directly cytoprotective, we found conditioned medium containing vascular endothelial growth factor from naproxen-treated CFSC-8B cells protected hepatocytes from carbon tetrachloride toxicity. Therefore, naproxen was capable of ameliorating toxic liver injury, which involved naproxen-induced release of

Functional and cellular responses to laser injury in the rat snake retina

NASA Astrophysics Data System (ADS)

Glickman, Randolph D.; Elliott, W. Rowe, III; Kumar, Neeru

2007-02-01

Acute (1-hr, 6-hr) and longer term (24-hr) effects of laser injury on retinal function and cellular responses have been studied in the Great Plains rat snake, Elaphe guttata emoryi. This animal is of interest for vision research because its eye has an all-cone retina. A linear array of 5 thermal lesions was placed in the retina of anesthetized animals, near the area centralis, using a Nd:VO 4 laser (532 nm), that delivered 50 mW per 10-msec pulse. Retinal function was assessed with the pattern electroretinogram (PERG), recorded before and after the placement of the lesions. PERGs were elicited with counterphased square-wave gratings, and were analyzed by Fourier analysis. The fate of lesioned cells was assessed by immunohistological staining for the transcription factor, NF-κB (which is activated by ionizing and nonionizing radiation), as well as for the apoptosis marker, caspase-9. The normal snake PERG had the maximum, real amplitude frequency component, determined by Fourier analysis, at the reversal frequency of the grating (i.e. shifts/sec). In the hour following the lesion-producing laser exposures, the PERG response exhibited frequency doubling, i.e. a new response waveform appeared at twice the reversal frequency. By 24-hr post exposure, many lesioned photoreceptors stained positively for both NF-κB and caspase 9. Because the PERG largely reflects retinal ganglion cell activity, the appearance of frequency doubling in the PERG suggests that complementary (push-pull) inputs to ganglion cells are disrupted by the laser lesions. The immunohistological results indicate that activation of NF- B is not necessarily associated with photoreceptor survival after a laser injury.

Molecular mechanisms of liver ischemia reperfusion injury: Insights from transgenic knockout models

PubMed Central

Datta, Gourab; Fuller, Barry J; Davidson, Brian R

2013-01-01

Ischemia reperfusion injury is a major obstacle in liver resection and liver transplantation surgery. Understanding the mechanisms of liver ischemia reperfusion injury (IRI) and developing strategies to counteract this injury will therefore reduce acute complications in hepatic resection and transplantation, as well as expanding the potential pool of usable donor grafts. The initial liver injury is initiated by reactive oxygen species which cause direct cellular injury and also activate a cascade of molecular mediators leading to microvascular changes, increased apoptosis and acute inflammatory changes with increased hepatocyte necrosis. Some adaptive pathways are activated during reperfusion that reduce the reperfusion injury. IRI involves a complex interplay between neutrophils, natural killer T-cells cells, CD4+ T cell subtypes, cytokines, nitric oxide synthases, haem oxygenase-1, survival kinases such as the signal transducer and activator of transcription, Phosphatidylinositol 3-kinases/Akt and nuclear factor κβ pathways. Transgenic animals, particularly genetic knockout models, have become a powerful tool at elucidating mechanisms of liver ischaemia reperfusion injury and are complementary to pharmacological studies. Targeted disruption of the protein at the genetic level is more specific and maintained than pharmacological inhibitors or stimulants of the same protein. This article reviews the evidence from knockout models of liver IRI about the cellular and molecular mechanisms underlying liver IRI. PMID:23555157

Antinociceptive reflex alteration in acute posttraumatic headache following whiplash injury.

PubMed

Keidel, M; Rieschke, P; Stude, P; Eisentraut, R; van Schayck, R; Diener, H

2001-06-01

Brainstem-mediated antinociceptive inhibitory reflexes of the temporalis muscle were investigated in 82 patients (47 F, 35 M, mean age 28.3 years, SD 9.4) with acute posttraumatic headache (PH) following whiplash injury but without neurological deficits, bone injury of the cervical spine or a combined direct head trauma on average 5 days after the acceleration trauma. Latencies and durations of the early and late exteroceptive suppression (ES1 and ES2) and the interposed EMG burst (IE) of the EMG of the voluntarily contracted right temporalis muscle evoked by ipsilateral stimulation of the second and third branches of the trigeminal nerve were analyzed and compared to a cohort of 82 normal subjects (43 F, 39 M, mean age 27.7 years, SD 7.1). Highly significant reflex alterations were found in patients with PH with a shortening of ES2 duration with delayed onset and premature ending as the primary parameter of this study, a moderate prolongation of ES1 and IE duration and a delayed onset of IE. The latency of ES1 was not significantly changed. These findings indicate that acute PH in whiplash injury is accompanied by abnormal antinociceptive brainstem reflexes. We conclude that the abnormality of the trigeminal inhibitory temporalis reflex is based on a transient dysfunction of the brainstem-mediated reflex circuit mainly of the late polysynaptic pathways. The reflex abnormalities are considered as a neurophysiological correlate of the posttraumatic (cervico)-cephalic pain syndrome. They point to an altered central pain control in acute PH due to whiplash injury.

Diagnosis and treatment of acute ankle injuries: development of an evidence-based algorithm

PubMed Central

Polzer, Hans; Kanz, Karl Georg; Prall, Wolf Christian; Haasters, Florian; Ockert, Ben; Mutschler, Wolf; Grote, Stefan

2011-01-01

Acute ankle injuries are among the most common injuries in emergency departments. However, there are still no standardized examination procedures or evidence-based treatment. Therefore, the aim of this study was to systematically search the current literature, classify the evidence, and develop an algorithm for the diagnosis and treatment of acute ankle injuries. We systematically searched PubMed and the Cochrane Database for randomized controlled trials, meta-analyses, systematic reviews or, if applicable, observational studies and classified them according to their level of evidence. According to the currently available literature, the following recommendations have been formulated: i) the Ottawa Ankle/Foot Rule should be applied in order to rule out fractures; ii) physical examination is sufficient for diagnosing injuries to the lateral ligament complex; iii) classification into stable and unstable injuries is applicable and of clinical importance; iv) the squeeze-, crossed leg- and external rotation test are indicative for injuries of the syndesmosis; v) magnetic resonance imaging is recommended to verify injuries of the syndesmosis; vi) stable ankle sprains have a good prognosis while for unstable ankle sprains, conservative treatment is at least as effective as operative treatment without the related possible complications; vii) early functional treatment leads to the fastest recovery and the least rate of reinjury; viii) supervised rehabilitation reduces residual symptoms and re-injuries. Taken these recommendations into account, we present an applicable and evidence-based, step by step, decision pathway for the diagnosis and treatment of acute ankle injuries, which can be implemented in any emergency department or doctor's practice. It provides quality assurance for the patient and promotes confidence in the attending physician. PMID:22577506

Psychological Characteristics in Acute Mild Traumatic Brain Injury: An MMPI-2 Study.

PubMed

Gass, Carlton S; Rogers, David; Kinne, Erica

2017-01-01

The psychological characteristics of acute traumatic brain injury (TBI) have received limited research focus, despite empirical evidence of their relevance for subsequent psychological adjustment and early therapeutic intervention. This study addressed a wide range of psychological features in 47 individuals who were hospitalized as a result of acute mild TBI (mTBI). Participants were screened from amongst consecutive TBI admissions for moderate to severe brain injury, and for pre-injury neurological, psychiatric, or substance abuse histories. Clinical and content scale scores on the MMPI-2 were explored in relation to patient gender, age, level of education, and extent of cognitive complaints. The results revealed diverse psychosocial problem areas across the sample, the most common of which were somatic and cognitive complaints, compromised insight, and a naively optimistic self-perception. The mediating roles of injury severity and demographic variables are discussed. Clinical implications and specific recommendations are presented.

Inhibition of neuronal nitric oxide synthase in ovine model of acute lung injury*

PubMed Central

Enkhbaatar, Perenlei; Connelly, Rhykka; Wang, Jianpu; Nakano, Yoshimitsu; Lange, Matthias; Hamahata, Atsumori; Horvath, Eszter; Szabo, Csaba; Jaroch, Stefan; Hölscher, Peter; Hillmann, Margrit; Traber, Lillian D.; Schmalstieg, Frank C.; Herndon, David N.; Traber, Daniel L.

2013-01-01

Objective Acute respiratory distress syndrome/acute lung injury is a serious complication of burn patients with concomitant smoke inhalation injury. Nitric oxide has been shown to play a major role in pulmonary dysfunction from thermal damage. In this study, we have tested the hypothesis that inhibition of neuronal nitric oxide synthase could ameliorate the severity of acute lung injury using our well-established ovine model of cutaneous burn and smoke inhalation. Design Prospective, randomized, controlled, experimental animals study. Setting Investigational intensive care unit at university hospital. Subjects Adult female sheep Interventions Female sheep (n = 16) were surgically prepared for the study. Seven days after surgery, all sheep were randomly allocated into three study groups: sham (noninjured, nontreated, n = 6); control (injured, treated with saline, n = 6); and neuronal nitric oxide synthase (injured, treated with specific neuronal nitric oxide synthase inhibitor, ZK 234238 (n = 4). Control and neuronal nitric oxide synthase groups were given a cutaneous burn (40% of total body surface, third degree) and insufflated with cotton smoke (48 breaths, <40°C) under halothane anesthesia. Animals in sham group received fake injury also under halothane anesthesia. After injury or fake injury procedure, all sheep were placed on ventilators and resuscitated with lactated Ringer's solution. Neuronal nitric oxide synthase group was administered with continuous infusion of ZK 234238 started 1 hr postinjury with a dose of 100 μg/kg/hr. Sham and control groups received same amount of saline. Measurements and Main Results Cardiopulmonary hemodynamics monitored during the 24-hr experimental time period was stable in the sham group. Control sheep developed multiple signs of acute lung injury. This pathophysiology included decreased pulmonary gas exchange and lung compliance, increased pulmonary edema, and inflammatory indices, such as interleukin-8. Treatment of

Albumin infusion improves renal blood flow autoregulation in patients with acute decompensation of cirrhosis and acute kidney injury.

PubMed

Garcia-Martinez, Rita; Noiret, Lorette; Sen, Sambit; Mookerjee, Rajeshwar; Jalan, Rajiv

2015-02-01

In cirrhotic patients with renal failure, renal blood flow autoregulation curve is shifted to the right, which is consequent upon sympathetic nervous system activation and endothelial dysfunction. Albumin infusion improves renal function in cirrhosis by mechanisms that are incompletely understood. We aimed to determine the effect of albumin infusion on systemic haemodynamics, renal blood flow, renal function and endothelial function in patients with acute decompensation of cirrhosis and acute kidney injury. Twelve patients with refractory ascites and 10 patients with acute decompensation of cirrhosis and acute kidney injury were studied. Both groups were treated with intravenous albumin infusion, 40-60 g/days over 3-4 days. Cardiac and renal haemodynamics were measured. Endothelial activation/dysfunction was assessed using von Willebrand factor and serum nitrite levels. F2α Isoprostanes, resting neutrophil burst and noradrenaline levels were quantified as markers of oxidative stress, endotoxemia and sympathetic activation respectively. Albumin infusion leads to a shift in the renal blood flow autoregulation curve towards normalization, which resulted in a significant increase in renal blood flow. Accordingly, improvement of renal function was observed. In parallel, a significant decrease in sympathetic activation, inflammation/oxidative stress and endothelial activation/dysfunction was documented. Improvement of renal blood flow correlated with improvement in endothelial activation (r = 0.741, P < 0.001). The data suggest that albumin infusion improves renal function in acutely decompensated cirrhotic patients with acute kidney injury by impacting on renal blood flow autoregulation. This is possibly achieved through endothelial stabilization and a reduction in the sympathetic tone, endotoxemia and oxidative stress. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Update on traumatic acute spinal cord injury. Part 2.

PubMed

Mourelo Fariña, M; Salvador de la Barrera, S; Montoto Marqués, A; Ferreiro Velasco, M E; Galeiras Vázquez, R

The aim of treatment in acute traumatic spinal cord injury is to preserve residual neurologic function, avoid secondary injury, and restore spinal alignment and stability. In this second part of the review, we describe the management of spinal cord injury focusing on issues related to short-term respiratory management, where the preservation of diaphragmatic function is a priority, with prediction of the duration of mechanical ventilation and the need for tracheostomy. Surgical assessment of spinal injuries based on updated criteria is discussed, taking into account that although the type of intervention depends on the surgical team, nowadays treatment should afford early spinal decompression and stabilization. Within a comprehensive strategy in spinal cord injury, it is essential to identify and properly treat patient anxiety and pain associated to spinal cord injury, as well as to prevent and ensure the early diagnosis of complications secondary to spinal cord injury (thromboembolic disease, gastrointestinal and urinary disorders, pressure ulcers). Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Involvement of TGF-β1/Smad3 Signaling in Carbon Tetrachloride-Induced Acute Liver Injury in Mice

PubMed Central

Niu, Liman; Cui, Xueling; Qi, Yan; Xie, Dongxue; Wu, Qian; Chen, Xinxin; Ge, Jingyan; Liu, Zhonghui

2016-01-01

Transforming growth factor-beta1 (TGF-β1) is a major factor in pathogenesis of chronic hepatic injury. Carbon tetrachloride (CCl4) is a liver toxicant, and CCl4-induced liver injury in mouse is a classical animal model of chemical liver injury. However, it is still unclear whether TGF-β1 is involved in the process of CCl4-induced acute chemical liver injury. The present study aimed to evaluate the role of TGF-β1 and its signaling molecule Smad3 in the acute liver injury induce by CCl4. The results showed that CCl4 induced acute liver injury in mice effectively confirmed by H&E staining of liver tissues, and levels of not only liver injury markers serum ALT and AST, but also serum TGF-β1 were elevated significantly in CCl4-treated mice, compared with the control mice treated with olive oil. Our data further revealed that TGF-β1 levels in hepatic tissue homogenate increased significantly, and type II receptor of TGF-β (TβRII) and signaling molecules Smad2, 3, mRNA expressions and Smad3 and phospho-Smad3 protein levels also increased obviously in livers of CCl4-treated mice. To clarify the effect of the elevated TGF-β1/Smad3 signaling on CCl4-induced acute liver injury, Smad3 in mouse liver was overexpressed in vivo by tail vein injection of Smad3-expressing plasmids. Upon CCl4 treatment, Smad3-overexpressing mice showed more severe liver injury identified by H&E staining of liver tissues and higher serum ALT and AST levels. Simultaneously, we found that Smad3-overexpressing mice treated with CCl4 showed more macrophages and neutrophils infiltration in liver and inflammatory cytokines IL-1β and IL-6 levels increment in serum when compared with those in control mice treated with CCl4. Moreover, the results showed that the apoptosis of hepatocytes increased significantly, and apoptosis-associated proteins Bax, cytochrome C and the cleaved caspase 3 expressions were up-regulated in CCl4-treated Smad3-overexpressing mice as well. These results suggested that TGF

Acute knee injuries: use of decision rules for selective radiograph ordering.

PubMed

Tandeter, H B; Shvartzman, P; Stevens, Max A

1999-12-01

Family physicians often encounter patients with acute knee trauma. Radiographs of injured knees are commonly ordered, even though fractures are found in only 6 percent of such patients and emergency department physicians can usually discriminate clinically between fracture and nonfracture. Decision rules have been developed to reduce the unnecessary use of radiologic studies in patients with acute knee injury. The Ottawa knee rules and the Pittsburgh decision rules are the latest guidelines for the selective use of radiographs in knee trauma. Application of these rules may lead to a more efficient evaluation of knee injuries and a reduction in health costs without an increase in adverse outcomes.

Association between preoperative hydration status and acute kidney injury in patients managed surgically for kidney tumours.

PubMed

Ellis, Robert J; Del Vecchio, Sharon J; Kalma, Benjamin; Ng, Keng Lim; Morais, Christudas; Francis, Ross S; Gobe, Glenda C; Ferris, Rebekah; Wood, Simon T

2018-07-01

The purpose of this study was to investigate whether preoperative dehydration and intraoperative hypotension were associated with postoperative acute kidney injury in patients managed surgically for kidney tumours. A retrospective analysis of 184 patients who underwent nephrectomy at a single centre was performed, investigating associations between acute kidney injury after nephrectomy, and both intraoperative hypotension and preoperative hydration/volume status. Intraoperative hypotension was defined as mean arterial pressure < 60 mmHg for ≥ 5 min. Urine conductivity was evaluated as a surrogate measure of preoperative hydration (euhydrated < 15 mS/cm; mildly dehydrated 15-20 mS/cm; dehydrated > 20 mS/cm). Multivariable logistic regression was used to evaluate associations between exposures and the primary outcome, with adjustment made for potential confounders. Patients who were dehydrated and mildly dehydrated had an increased risk of acute kidney injury (adjusted odds ratio [aOR] 4.1, 95% CI 1.3-13.5; and aOR 2.4, 95% CI 1.1-5.3, respectively) compared with euhydrated patients (p = 0.009). Surgical approach appeared to modify this effect, where dehydrated patients undergoing laparoscopic surgery were most likely to develop acute kidney injury, compared with patients managed using an open approach. Intraoperative hypotension was not associated with acute kidney injury. Preoperative dehydration may be associated with postoperative acute kidney injury. Avoiding dehydration in the preoperative period may be advisable, and adherence to international evidence-based guidelines on preoperative fasting is recommended.

Accumulated workloads and the acute:chronic workload ratio relate to injury risk in elite youth football players

PubMed Central

Bowen, Laura; Gross, Aleksander Stefan; Gimpel, Mo; Li, François-Xavier

2017-01-01

Aim The purpose of this study was to investigate the relationship between physical workload and injury risk in elite youth football players. Methods The workload data and injury incidence of 32 players were monitored throughout 2 seasons. Multiple regression was used to compare cumulative (1, 2, 3 and 4-weekly) loads and acute:chronic (A:C) workload ratios (acute workload divided by chronic workload) between injured and non-injured players for specific GPS and accelerometer-derived variables:total distance (TD), high-speed distance (HSD), accelerations (ACC) and total load. Workloads were classified into discrete ranges by z-scores and the relative risk was determined. Results A very high number of ACC (≥9254) over 3 weeks was associated with the highest significant overall (relative risk (RR)=3.84) and non-contact injury risk (RR=5.11). Non-contact injury risk was significantly increased when a high acute HSD was combined with low chronic HSD (RR=2.55), but not with high chronic HSD (RR=0.47). Contact injury risk was greatest when A:C TD and ACC ratios were very high (1.76 and 1.77, respectively) (RR=4.98). Conclusions In general, higher accumulated and acute workloads were associated with a greater injury risk. However, progressive increases in chronic workload may develop the players' physical tolerance to higher acute loads and resilience to injury risk. PMID:27450360

Expression and Cellular Distribution of Ubiquitin in Response to Injury in the Developing Spinal Cord of Monodelphis domestica

PubMed Central

Noor, Natassya M.; Møllgård, Kjeld; Wheaton, Benjamin J.; Steer, David L.; Truettner, Jessie S.; Dziegielewska, Katarzyna M.; Dietrich, W. Dalton; Smith, A. Ian; Saunders, Norman R.

2013-01-01

Ubiquitin, an 8.5 kDa protein associated with the proteasome degradation pathway has been recently identified as differentially expressed in segment of cord caudal to site of injury in developing spinal cord. Here we describe ubiquitin expression and cellular distribution in spinal cord up to postnatal day P35 in control opossums (Monodelphis domestica) and in response to complete spinal transection (T10) at P7, when axonal growth through site of injury occurs, and P28 when this is no longer possible. Cords were collected 1 or 7 days after injury, with age-matched controls and segments rostral to lesion were studied. Following spinal injury ubiquitin levels (western blotting) appeared reduced compared to controls especially one day after injury at P28. In contrast, after injury mRNA expression (qRT-PCR) was slightly increased at P7 but decreased at P28. Changes in isoelectric point of separated ubiquitin indicated possible post-translational modifications. Cellular distribution demonstrated a developmental shift between earliest (P8) and latest (P35) ages examined, from a predominantly cytoplasmic immunoreactivity to a nuclear expression; staining level and shift to nuclear staining was more pronounced following injury, except 7 days after transection at P28. After injury at P7 immunostaining increased in neurons and additionally in oligodendrocytes at P28. Mass spectrometry showed two ubiquitin bands; the heavier was identified as a fusion product, likely to be an ubiquitin precursor. Apparent changes in ubiquitin expression and cellular distribution in development and response to spinal injury suggest an intricate regulatory system that modulates these responses which, when better understood, may lead to potential therapeutic targets. PMID:23626776

Arterial injury associated with acute compartment syndrome of the thigh following blunt trauma.

PubMed

Suzuki, Takashi; Moirmura, Naoto; Kawai, Kousei; Sugiyama, Mitsugi

2005-01-01

Acute compartment syndrome of the thigh is a rare condition, and the basic causes of high pressure within a muscle compartment have been considered to be intramuscular haematoma and soft-tissue oedema. However, the importance of arterial injury has not been well recognized. Among 3658 blunt trauma patients admitted to our Level 1 Trauma Centre between 1994 and 2001, there were eight patients (nine thighs) who had undergone emergency fasciotomy and these were the subjects of the present study. Arteriography of the proximal lower limb had been performed after the fasciotomy in patients with prolonged hypotension and persistent bleeding from the fasciotomy wound. All the patients had sustained high-energy trauma, systemic hypotension and local trauma to the proximal lower limb. Among them, four (five thighs) had undergone arteriography and four (four thighs) were confirmed as having sustained arterial injuries. In those patients with definitive arterial injuries, the time from injury to the onset of the compartment syndrome was less than 5 h. Acute compartment syndrome of the thigh in blunt trauma patients may be the result of associated arterial injuries. It is suggested that patients with local trauma to the proximal lower limb who exhibit an acute compartment syndrome together with haemodynamic instability should undergo arteriography soon after fasciotomy.

Worldwide Steroid Prescription for Acute Spinal Cord Injury

PubMed Central

Falavigna, Asdrubal; Quadros, Francine W.; Teles, Alisson R.; Wong, Chung Chek; Barbagallo, Giuseppe; Brodke, Darrel; Al-Mutair, Abdulaziz; Riew, K. Daniel

2018-01-01

Study Design: Cross-sectional study. Objectives: To continue the line of a previous publication using steroid for acute spinal cord injury (SCI) by spine surgeons from Latin America (LA) and assess the current status of methylprednisolone (MP) prescription in Europe (EU), Asia Pacific (AP), North America (NA), and Middle East (ME) to determine targets for educational activities suitable for each region. Methods: The English version of a previously published questionnaire was used to evaluate opinions about MP administration in acute SCI in LA, EU, AP, NA, and ME. This Internet-based survey was conducted by members of AOSpine. The questionnaire asked about demographic features, background with management of spine trauma patients, routine administration of MP in acute SCI, and reasons for MP administration. Results: A total of 2659 responses were obtained for the electronic questionnaire from LA, EU, AP, NA, and ME. The number of spine surgeons that treat SCI was 2206 (83%). The steroid was used by 1198 (52.9%) surgeons. The uses of MP were based predominantly on the National Acute Spinal Cord Injury Study III study (n = 595, 50%). The answers were most frequently given by spine surgeons from AP, ME, and LA. These regions presented a statistically significant difference from North America (P < .001). The number of SCI patients treated per year inversely influenced the use of MP. The higher the number of patients treated, the lower the administration rates of MP observed. Conclusions: The study identified potential targets for educational campaigns, aiming to reduce inappropriate practices of MP administration. PMID:29796379

Acute kidney injury post-major orthopaedic surgery: A single-Centre case-control study.

PubMed

Ying, Tracey; Chan, Samantha; Lane, Stephen; Somerville, Christine

2018-02-01

To identify risk factors for acute kidney injury following major orthopaedic surgery. We included all patients undergoing major orthopaedic surgery at University Hospital Geelong between 2008 and 2014 in the study. Out of 2188 surgeries audited, we identified cases of acute kidney injury using the RIFLE criteria and matched those to controls 2:1 for age, sex, procedure and chronic kidney disease stage. We reviewed their records for risk factors of postoperative acute kidney injury, including medications such as gentamicin, diuretics, non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use. We reviewed the patients' history of cardiovascular disease, chronic liver disease, hypertension and diabetes mellitus along with presence of sepsis and obesity. Associations of hypothetical risk factors were estimated using conditional logistic regression. We identified 164 cases of AKI in an elderly cohort (median age = 73 years). Controlling for baseline comorbidities, both diuretic and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use were found to be associated with a twofold risk of acute kidney injury (diuretic - OR 2.06 95% CI:1.30-3.26, P < 0.005, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use OR 2.09 95% CI:1.31-3.32, P < 0.005). A dose-effect model accounting for perioperative nonsteroidal anti-inflammatory drug administration demonstrated a linear relationship between the number of times these drugs were given and postoperative acute kidney injury risk (OR 1.35 95% CI:1.05-1.73, P = 0.02). We identified perioperative diuretics, non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to be significantly associated with postoperative AKI. Further prospective studies are required to confirm this. © 2016 Asian Pacific Society of Nephrology.

The Role of Alveolar Macrophage Beta-2 Adrenergic Receptors in Acute Lung Injury

DTIC Science & Technology

2017-10-01

macrophages contributes to Acute Respiratory Distress Syndrome , which is a significant contributor to morbidity and mortality in military and civilian settings...carbonic anhydrase (Ca2). 15. SUBJECT TERMS Acute lung injury, Acute Respiratory Distress Syndrome , ARDS, pulmonary edema, influenza, viral pneumonia...to understand how β2AR signaling in macrophages contributes to Acute Respiratory Distress Syndrome (ARDS). ARDS is a significant contributor to

Reversal of anemia with allogenic RBC transfusion prevents post-cardiopulmonary bypass acute kidney injury in swine

PubMed Central

Patel, Nishith N.; Lin, Hua; Toth, Tibor; Welsh, Gavin I.; Jones, Ceri; Ray, Paramita; Satchell, Simon C.; Sleeman, Philippa; Angelini, Gianni D.

2011-01-01

Anemia during cardiopulmonary bypass (CPB) is strongly associated with acute kidney injury in clinical studies; however, reversal of anemia with red blood cell (RBC) transfusions is associated with further renal injury. To understand this paradox, we evaluated the effects of reversal of anemia during CPB with allogenic RBC transfusion in a novel large-animal model of post-cardiac surgery acute kidney injury with significant homology to that observed in cardiac surgery patients. Adult pigs undergoing general anesthesia were allocated to a Sham procedure, CPB alone, Sham+RBC transfusion, or CPB+RBC transfusion, with recovery and reassessment at 24 h. CPB was associated with dilutional anemia and caused acute kidney injury in swine characterized by renal endothelial dysfunction, loss of nitric oxide (NO) bioavailability, vasoconstriction, medullary hypoxia, cortical ATP depletion, glomerular sequestration of activated platelets and inflammatory cells, and proximal tubule epithelial cell stress. RBC transfusion in the absence of CPB also resulted in renal injury. This was characterized by endothelial injury, microvascular endothelial dysfunction, platelet activation, and equivalent cortical tubular epithelial phenotypic changes to those observed in CPB pigs, but occurred in the absence of severe intrarenal vasoconstriction, ATP depletion, or reductions in creatinine clearance. In contrast, reversal of anemia during CPB with RBC transfusion prevented the reductions in creatinine clearance, loss of NO bioavailability, platelet activation, inflammation, and epithelial cell injury attributable to CPB although it did not prevent the development of significant intrarenal vasoconstriction and endothelial dysfunction. In conclusion, contrary to the findings of observational studies in cardiac surgery, RBC transfusion during CPB protects pigs against acute kidney injury. Our study underlines the need for translational research into indications for transfusion and prevention

Endovascular Treatment in Emergency Setting of Acute Arterial Injuries After Orthopedic Surgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carrafiello, Gianpaolo, E-mail: gcarraf@tin.it; Fontana, Federico, E-mail: fede.fontana@libero.it; Mangini, Monica, E-mail: monica.mangini@tin.it

Purpose: To assess the feasibility and effectiveness of emergency endovascular treatment of acute arterial injuries after orthopedic surgery. Materials and Methods: Fifteen patients (mean age 68.3 years) with acute arterial injuries after orthopedic surgery were observed, in particular, 5 patients with pseudoaneurysm, 9 patients with active bleeding, and 1 patient with arterial dissection. Transarterial embolization (TAE) and positioning of covered and noncovered stents were the treatments performed. Follow-up after stent implantation (mean 36 months) was performed with color Doppler US (CDU) at 1, 3, 6, and 12 months and yearly thereafter. Plain X-ray was performed to evidence dislodgment or fracturemore » of the graft. A minimum of 12 months' follow-up is available after TAE. Results: Immediate technical success was obtained in all cases. No major complications occurred. Overall clinical success rate was 100%. During mean follow-up, stent-graft occlusions did not occurred. No recurrence and/or consequence of TAE was registered during a minimum follow-up of 12 months. Conclusions: Percutaneous treatment is a feasible and safe tool for treating arterial injuries because it can provide fast and definitive resolution of the damage. This low-invasiveness approach can be proposed as first-line treatment in patients with acute injuries after orthopedic surgery.« less

The Crucial Role of Early Mitochondrial Injury in L-Lysine-Induced Acute Pancreatitis

PubMed Central

Biczó, György; Hegyi, Péter; Dósa, Sándor; Shalbuyeva, Natalia; Berczi, Sándor; Sinervirta, Riitta; Hracskó, Zsuzsanna; Siska, Andrea; Kukor, Zoltán; Jármay, Katalin; Venglovecz, Viktória; Varga, Ilona S.; Iványi, Béla; Alhonen, Leena; Wittmann, Tibor; Gukovskaya, Anna; Takács, Tamás

2011-01-01

Abstract Aims Large doses of intraperitoneally injected basic amino acids, L-arginine, or L-ornithine, induce acute pancreatitis in rodents, although the mechanisms mediating pancreatic toxicity remain unknown. Another basic amino acid, L-lysine, was also shown to cause pancreatic acinar cell injury. The aim of the study was to get insight into the mechanisms through which L-lysine damages the rat exocrine pancreas, in particular to characterize the kinetics of L-lysine-induced mitochondrial injury, as well as the pathologic responses (including alteration of antioxidant systems) characteristic of acute pancreatitis. Results We showed that intraperitoneal administration of 2 g/kg L-lysine induced severe acute necrotizing pancreatitis. L-lysine administration caused early pancreatic mitochondrial damage that preceded the activation of trypsinogen and the proinflammatory transcription factor nuclear factor-κB (NF-κB), which are commonly thought to play an important role in the development of acute pancreatitis. Our data demonstrate that L-lysine impairs adenosine triphosphate synthase activity of isolated pancreatic, but not liver, mitochondria. Innovation and Conclusion Taken together, early mitochondrial injury caused by large doses of L-lysine may lead to the development of acute pancreatitis independently of pancreatic trypsinogen and NF-κB activation. PMID:21644850

AP214, an analogue of α-melanocyte-stimulating hormone, ameliorates sepsis-induced acute kidney injury and mortality

PubMed Central

Doi, Kent; Hu, Xuzhen; Yuen, Peter S.T.; Leelahavanichkul, Asada; Yasuda, Hideo; Kim, Soo Mi; Schnermann, Jürgen; Jonassen, Thomas E.N.; Frøkiær, Jørgen; Nielsen, Søren; Star, Robert A.

2008-01-01

Sepsis remains a serious problem in critically ill patients with the mortality increasing to over half when there is attendant acute kidney injury. α-Melanocyte-stimulating hormone is a potent anti-inflammatory cytokine that inhibits many forms of inflammation including that with acute kidney injury. We tested whether a new α-melanocyte-stimulating hormone analogue (AP214), which has increased binding affinity to melanocortin receptors, improves sepsis-induced kidney injury and mortality using a cecal ligation and puncture mouse model. In the lethal cecal ligation-puncture model of sepsis, severe hypotension and bradycardia resulted and AP214 attenuated acute kidney injury of the lethal model with a bell-shaped dose-response curve. An optimum AP214 dose reduced acute kidney injury even when it was administered 6 hr after surgery and it significantly improved blood pressure and heart rate. AP214 reduced serum TNF-α and IL-10 levels with a bell-shaped dose-response curve. Additionally; NF-κB activation in the kidney and spleen, and splenocyte apoptosis were decreased by the treatment. AP214 significantly improved survival in both lethal and sublethal models. We have shown that AP214 improves hemodynamic failure, acute kidney injury, mortality and splenocyte apoptosis attenuating pro- and anti-inflammatory actions due to sepsis. PMID:18354376

Amniotic fluid stem cells from EGFP transgenic mice attenuate hyperoxia-induced acute lung injury.

PubMed

Wen, Shih-Tao; Chen, Wei; Chen, Hsiao-Ling; Lai, Cheng-Wei; Yen, Chih-Ching; Lee, Kun-Hsiung; Wu, Shinn-Chih; Chen, Chuan-Mu

2013-01-01

High concentrations of oxygen aggravate the severity of lung injury in patients requiring mechanical ventilation. Although mesenchymal stem cells have been shown to effectively attenuate various injured tissues, there is limited information regarding a role for amniotic fluid stem cells (AFSCs) in treating acute lung injury. We hypothesized that intravenous delivery of AFSCs would attenuate lung injury in an experimental model of hyperoxia-induced lung injury. AFSCs were isolated from EGFP transgenic mice. The in vitro differentiation, surface markers, and migration of the AFSCs were assessed by specific staining, flow cytometry, and a co-culture system, respectively. The in vivo therapeutic potential of AFSCs was evaluated in a model of acute hyperoxia-induced lung injury in mice. The administration of AFSCs significantly reduced the hyperoxia-induced pulmonary inflammation, as reflected by significant reductions in lung wet/dry ratio, neutrophil counts, and the level of apoptosis, as well as reducing the levels of inflammatory cytokine (IL-1β, IL-6, and TNF-α) and early-stage fibrosis in lung tissues. Moreover, EGFP-expressing AFSCs were detected and engrafted into a peripheral lung epithelial cell lineage by fluorescence microscopy and DAPI stain. Intravenous administration of AFSCs may offer a new therapeutic strategy for acute lung injury (ALI), for which efficient treatments are currently unavailable.

Role of activin A in carbon tetrachloride-induced acute liver injury.

PubMed

Wang, Dong-Hui; Wang, Yi-Nan; Ge, Jing-Yan; Liu, Hai-Yan; Zhang, Hong-Jun; Qi, Yan; Liu, Zhong-Hui; Cui, Xue-Ling

2013-06-28

To investigate the expression and role of activin A in a mouse model of acute chemical liver injury. Acute liver injury in C57BL/6 male mice was induced by intraperitoneal injection with carbon tetrachloride (CCl4) (0.5 mL/kg, body weight) dissolved in olive oil (1:19 v/v). Mice were sacrificed 1, 3, 5 and 7 d after the treatment. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were examined and pathological changes of liver observed by hematoxylin and eosin staining to evaluate the liver injury. Activin A protein levels in serum and hepatic tissue homogenate of mice were detected by enzyme-linked immunosorbent assay, and the expression pattern of activin A protein in livers of mice was examined by immunohistochemistry. Activin type IIA receptor (ActRIIA) and Smad3 expressions in the liver were analyzed by real-time quantitative reverse transcription-polymerase chain reaction. In order to further investigate the role of activin A, we also utilized activin A blocking experiment by anti-activin A antibody (500 μg/kg, body weight) injection into mouse tail vein. In CCl4-treated mice, serum ALT and AST levels were significantly increased, compared with that in control mice (P < 0.01). Furthermore, the serious necrosis was observed around hepatic portal areas in CCl4-treated mice. Simultaneously, activin A levels in serum and hepatic tissue homogenate of mice treated with CCl4 for 1, 3 and 5 d increased significantly, compared with that in control mice (P < 0.01). Activin A protein expression in hepatocytes not within the necrotic area was also upregulated in mice following CCl4 treatment. Not only activin A, but also ActRIIA and activin signaling molecule Smad3 mRNA expressions in injury liver induced by CCl4 were significantly higher than that in control liver. In addition, levels of serum ALT and AST in CCl4-treated mice were significantly decreased by injection of anti-activin A antibody to block endogenous activin A

Acute Injuries among Professional Boxers in New York State: A Two-Year Survey.

ERIC Educational Resources Information Center

Jordan, Barry D.; Campbell, Edwin A.

1988-01-01

From August 1982 through July 1984, all acute boxing injuries among professional boxers in New York State were reviewed in order to classify them as craniocerebral or other injuries. Results and methodology are discussed. (Author/MT)

The Epidemiology of Transfusion-related Acute Lung Injury Varies According to the Applied Definition of Lung Injury Onset Time.

PubMed

Vande Vusse, Lisa K; Caldwell, Ellen; Tran, Edward; Hogl, Laurie; Dinwiddie, Steven; López, José A; Maier, Ronald V; Watkins, Timothy R

2015-09-01

Research that applies an unreliable definition for transfusion-related acute lung injury (TRALI) may draw false conclusions about its risk factors and biology. The effectiveness of preventive strategies may decrease as a consequence. However, the reliability of the consensus TRALI definition is unknown. To prospectively study the effect of applying two plausible definitions of acute respiratory distress syndrome onset time on TRALI epidemiology. We studied 316 adults admitted to the intensive care unit and transfused red blood cells within 24 hours of blunt trauma. We identified patients with acute respiratory distress syndrome, and defined acute respiratory distress syndrome onset time two ways: (1) the time at which the first radiographic or oxygenation criterion was met, and (2) the time both criteria were met. We categorized two corresponding groups of TRALI cases transfused in the 6 hours before acute respiratory distress syndrome onset. We used Cohen's kappa to measure agreement between the TRALI cases and implicated blood components identified by the two acute respiratory distress syndrome onset time definitions. In a nested case-control study, we examined potential risk factors for each group of TRALI cases, including demographics, injury severity, and characteristics of blood components transfused in the 6 hours before acute respiratory distress syndrome onset. Forty-two of 113 patients with acute respiratory distress syndrome were TRALI cases per the first acute respiratory distress syndrome onset time definition and 63 per the second definition. There was slight agreement between the two groups of TRALI cases (κ = 0.16; 95% confidence interval, -0.01 to 0.33) and between the implicated blood components (κ = 0.15, 95% confidence interval, 0.11-0.20). Age, Injury Severity Score, high plasma-volume components, and transfused plasma volume were risk factors for TRALI when applying the second acute respiratory distress syndrome onset time definition

Acute kidney injury due to tropical infectious diseases and animal venoms: a tale of 2 continents.

PubMed

Burdmann, Emmanuel A; Jha, Vivekanand

2017-05-01

South and Southeast Asia and Latin American together comprise 46 countries and are home to approximately 40% of the world population. The sociopolitical and economic heterogeneity, tropical climate, and malady transitions characteristic of the region strongly influence disease behavior and health care delivery. Acute kidney injury epidemiology mirrors these inequalities. In addition to hospital-acquired acute kidney injury in tertiary care centers, these countries face a large preventable burden of community-acquired acute kidney injury secondary to tropical infectious diseases or animal venoms, affecting previously healthy young individuals. This article reviews the epidemiology, clinical picture, prevention, risk factors, and pathophysiology of acute kidney injury associated with tropical diseases (malaria, dengue, leptospirosis, scrub typhus, and yellow fever) and animal venom (snakes, bees, caterpillars, spiders, and scorpions) in tropical regions of Asia and Latin America, and discusses the potential future challenges due to emerging issues. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Renoprotective effects of asialoerythropoietin in diabetic mice against ischaemia-reperfusion-induced acute kidney injury.

PubMed

Nakazawa, Jun; Isshiki, Keiji; Sugimoto, Toshiro; Araki, Shin-Ichi; Kume, Shinji; Yokomaku, Yukiyo; Chin-Kanasaki, Masami; Sakaguchi, Masayoshi; Koya, Daisuke; Haneda, Masakazu; Kashiwagi, Atsunori; Uzu, Takashi

2010-02-01

Diabetic patients are at higher risk of failure to recover after acute kidney injury, however, the mechanism and therapeutic strategies remain unclear. Erythropoietin is cytoprotective in a variety of non-haematopoietic cells. The aim of the present study was to clarify the mechanism of diabetes-related acceleration of renal damage after ischaemia-reperfusion injury and to examine the therapeutic potential of asialoerythropoietin, a non-haematopoietic erythropoietin derivative, against ischaemia-reperfusion-induced acute kidney injury in diabetic mice. C57BL/6J mice with and without streptozotocin-induced diabetes were subjected to 30 min unilateral renal ischaemia-reperfusion injury at 1 week after induction of diabetes. They were divided into four group: (i) non-diabetic plus ischaemia-reperfusion injury; (ii) non-diabetic plus ischaemia-reperfusion injury plus asialoerythropoietin (3000 IU/kg bodyweight); (iii) diabetic plus ischaemia-reperfusion injury; and (iv) diabetic plus ischemia-reperfusion injury plus asialoerythropoietin. Experiments were conducted at the indicated time periods after ischaemia-reperfusion injury. Ischaemia-reperfusion injury of diabetic kidney resulted in significantly low protein expression levels of bcl-2, an anti-apoptotic molecule, and bone morphogenetic protein-7 (BMP-7), an anti-fibrotic and pro-regenerative factor, compared with non-diabetic kidneys. Diabetic kidney subsequently showed severe damage including increased tubular cell apoptosis, tubulointerstitial fibrosis and decreased tubular proliferation, compared with non-diabetic kidney. Treatment with asialoerythropoietin induced bcl-2 and BMP-7 expression in diabetic kidney and decreased tubular cell apoptosis, tubulointerstitial fibrosis and accelerated tubular proliferation. Reduced induction bcl-2 and BMP-7 may play a role in the acceleration of renal damage after ischaemia-reperfusion injury in diabetic kidney. The renoprotective effects of asialoerythropoietin on acute

An Immunoassay to Rapidly Measure Acetaminophen Protein Adducts Accurately Identifies Patients With Acute Liver Injury or Failure.

PubMed

Roberts, Dean W; Lee, William M; Hinson, Jack A; Bai, Shasha; Swearingen, Christopher J; Stravitz, R Todd; Reuben, Adrian; Letzig, Lynda; Simpson, Pippa M; Rule, Jody; Fontana, Robert J; Ganger, Daniel; Reddy, K Rajender; Liou, Iris; Fix, Oren; James, Laura P

2017-04-01

A rapid and reliable point-of-care assay to detect acetaminophen protein adducts in the serum of patients with acute liver injury could improve diagnosis and management. AcetaSTAT is a competitive immunoassay used to measure acetaminophen protein adducts formed by toxic metabolites in serum samples from patients. We compared the accuracy of AcetaSTAT vs high-pressure liquid chromatography with electrochemical detection (HPLC-EC; a sensitive and specific quantitative analytic assay) to detect acetaminophen protein adducts. We collected serum samples from 19 healthy individuals (no liver injury, no recent acetaminophen use), 29 patients without acetaminophen-associated acute liver injury, and 33 patients with acetaminophen-associated acute liver injury participating in the Acute Liver Failure Study Group registry. Each serum sample was analyzed by AcetaSTAT (reported as test band amplitude) and HPLC-EC (the reference standard). We also collected data on patient age, sex, weight, level of alanine aminotransferase on test day and peak values, concentration of acetaminophen, diagnoses (by site investigator and causality review committee), and outcome after 21 days. Differences between groups were analyzed using the Fisher exact test for categoric variables and the Kruskal-Wallis test or rank-sum test for continuous variables. AcetaSTAT discriminated between patients with and without acetaminophen-associated acute liver injury; the median AcetaSTAT test band amplitude for patients with acetaminophen-associated acute liver injury was 584 (range, 222-1027) vs 3678 (range, 394-8289) for those without (P < .001). AcetaSTAT identified patients with acetaminophen-associated acute liver injury with 100% sensitivity, 86.2% specificity, a positive predictive value of 89.2%, and a negative predictive value of 100%. Results from AcetaSTAT were positive in 4 subjects who received a causality review committee diagnosis of non-acetaminophen-associated acute liver injury; HPLC-EC and

Whole blood neutrophil gelatinase-associated lipocalin predicts acute kidney injury in burn patients.

PubMed

Sen, Soman; Godwin, Zack R; Palmieri, Tina; Greenhalgh, David; Steele, Amanda N; Tran, Nam K

2015-06-15

Early detection of acute kidney injury (AKI) in severely burn-injured patients can help alter treatment to prevent progression to acute failure and reduce the need for renal replacement therapy. We hypothesized that whole blood neutrophil gelatinase-associated lipocalin (NGAL) will be increased in severely burn-injured patients who develop AKI during acute resuscitation. We performed a prospective observation study of adult burn patients with a 20% total body surface area (TBSA) burned or greater burn injury. Two-hour serial measurements of NGAL, serum creatinine (Cr), and hourly urine output (UO) were collected for 48 h after admission. Our primary goal was to correlate the risk of AKI in the first week after burn injury with serial NGAL levels in the first 48 h after admission. Our secondary goal was to determine if NGAL was an earlier independent predictor of AKI compared with Cr and UO. We enrolled 30 adult (age ≥ 18 y) burn patients with the mean ± standard deviation age of 40.9 ± 15.4 and mean TBSA of 46.4 ± 22.4. Fourteen patients developed AKI within the first 7 d after burn injury. There were no differences in age, TBSA, fluid administration, mean arterial pressure, UO, and Cr between AKI and no-AKI patients. NGAL was significantly increased as early as 4 h after injury (182.67 ± 83.3 versus 107.37 ± 46.15) in the AKI group. Controlling for age, TBSA, and inhalation injury, NGAL was a predictor of AKI at 4 h after injury (odds ratio, 1.02) and remained predictive of AKI for the period of more than the first 24 h after admission. UO and Cr were not predictive of AKI in the first 24 h after admission. Whole blood NGAL is markedly increased in burn patients who develop AKI in the first week after injury. In addition, NGAL is an early independent predictor of AKI during acute resuscitation for severe burn injury. UO and Cr are not predictive of AKI during this time period. Copyright © 2015 Elsevier Inc. All rights reserved.

Acute kidney injury: how do we define it?

PubMed

Lewington, Andrew J P; Sayed, Ahmed

2010-01-01

Over recent years, there has been welcome increased interest in acute kidney injury (AKI) and its association with patient outcome. The term AKI has replaced the term acute renal failure (ARF) and encompasses all types of ARF. New definitions and staging systems for AKI have been proposed, which have stimulated a multitude of different studies to evaluate their clinical utility. These recent advances need to be communicated to the wider health care community so that we are using a shared nomenclature. In 2009 the National Confidential Enquiry into Patient Outcome and Death AKI study ('Adding Insult to Injury') announced its findings and recommendations. The report recommended that the detection of AKI and its management should be improved. These recommendations along with the adoption of the new staging systems will potentially have an impact on clinical biochemistry departments and exert an increased demand on resources. Running in parallel with these initiatives is the quest to discover novel biomarkers to detect AKI, the development and introduction of which will require laboratory support.

A retrospective analysis of the effect of blood transfusion on cerebral oximetry entropy and acute kidney injury.

PubMed

Engoren, Milo; Brown, Russell R; Dubovoy, Anna

2017-01-01

Acute anemia is associated with both cerebral dysfunction and acute kidney injury and is often treated with red blood cell transfusion. We sought to determine if blood transfusion changed the cerebral oximetry entropy, a measure of the complexity or irregularity of the oximetry values, and if this change was associated with subsequent acute kidney injury. This was a retrospective, case-control study of patients undergoing cardiac surgery with cardiopulmonary bypass at a tertiary care hospital, comparing those who received a red blood cell transfusion to those who did not. Acute kidney injury was defined as a perioperative increase in serum creatinine by ⩾26.4 μmol/L or by ⩾50% increase. Entropy was measured using approximate entropy, sample entropy, forbidden word entropy and basescale4 entropy in 500-point sets. Forty-four transfused patients were matched to 88 randomly selected non-transfused patients. All measures of entropy had small changes in the transfused group, but increased in the non-transfused group (p<0.05, for all comparisons). Thirty-five of 132 patients (27%) suffered acute kidney injury. Based on preoperative factors, patients who suffered kidney injury were similar to those who did not, including baseline cerebral oximetry levels. After analysis with hierarchical logistic regression, the change in basescale4 entropy (odds ratio = 1.609, 95% confidence interval = 1.057-2.450, p = 0.027) and the interaction between basescale entropy and transfusion were significantly associated with subsequent development of acute kidney injury. The transfusion of red blood cells was associated with a smaller rise in entropy values compared to non-transfused patients, suggesting a change in the regulation of cerebral oxygenation, and these changes in cerebral oxygenation are also associated with acute kidney injury.

Exacerbation of Acute Traumatic Brain Injury by Circulating Extracellular Vesicles.

PubMed

Hazelton, Isla; Yates, Abi; Dale, Ashley; Roodselaar, Jay; Akbar, Naveed; Ruitenberg, Marc J; Anthony, Daniel C; Couch, Yvonne

2018-02-15

Inflammatory lesions in the brain activate a systemic acute-phase response (APR), which is dependent on the release of extracellular vesicles (EVs) into the circulation. The resulting APR is responsible for regulating leukocyte mobilization and subsequent recruitment to the brain. Factors that either exacerbate or inhibit the APR will also exacerbate or inhibit central nervous system (CNS) inflammation as a consequence and have the potential to influence ongoing secondary damage. Here, we were interested to discover how the circulating EV population changes after traumatic brain injury (TBI) and how manipulation of the circulating EV pool impacts on the outcome of TBI. We found the number of circulating EVs increased rapidly post-TBI, and this was accompanied by an increase in CNS and hepatic leukocyte recruitment. In an adoptive transfer study, we then evaluated the outcomes of TBI after administering EVs derived from either in vitro macrophage or endothelial cell lines stimulated with lipopolysaccharide (LPS), or from murine plasma from an LPS challenge using the air-pouch model. By manipulating the circulating EV population, we were able to demonstrate that each population of transferred EVs increased the APR. However, the characteristics of the response were dependent on the nature of the EVs; specifically, it was significantly increased when animals were challenged with macrophage-derived EVs, suggesting that the cellular origins of EVs may determine their function. Selectively targeting EVs from macrophage/monocyte populations is likely to be of value in reducing the impact of the systemic inflammatory response on the outcome of traumatic CNS injury.

Inhibition of HDAC6 protects against rhabdomyolysis-induced acute kidney injury

PubMed Central

Shi, Yingfeng; Xu, Liuqing; Tang, Jinhua; Fang, Lu; Ma, Shuchen; Ma, Xiaoyan; Nie, Jing; Pi, Xiaoling; Qiu, Andong; Zhuang, Shougang

2017-01-01

Histone deacetylase 6 (HDAC6) inhibition has been reported to protect against ischemic stroke and prolong survival after sepsis in animal models. However, it remains unknown whether HDAC6 inhibition offers a renoprotective effect after acute kidney injury (AKI). In this study, we examined the effect of tubastatin A (TA), a highly selective inhibitor of HDAC6, on AKI in a murine model of glycerol (GL) injection-induced rhabdomyolysis. Following GL injection, the mice developed severe acute tubular injury as indicated by renal dysfunction; expression of neutrophil gelatinase-associated lipocalin (NGAL), an injury marker of renal tubules; and an increase of TdT-mediated dUTP nick-end labeling (TUNEL)-positive tubular cells. These changes were companied by increased HDAC6 expression in the cytoplasm of renal tubular cells. Administration of TA significantly reduced serum creatinine and blood urea nitrogen levels as well as attenuated renal tubular damage in injured kidneys. HDAC6 inhibition also resulted in decreased expression of NGAL, reduced apoptotic cell, and inactivated caspase-3 in the kidney after acute injury. Moreover, injury to the kidney increased phosphorylation of nuclear factor (NF)-κB and expression of multiple cytokines/chemokines including tumor necrotic factor-α and interleukin-6 and monocyte chemoattractant protein-1, as well as macrophage infiltration. Treatment with TA attenuated all those responses. Finally, HDAC6 inhibition reduced the level of oxidative stress by suppressing malondialdehyde (MDA) and preserving expression of superoxide dismutase (SOD) in the injured kidney. Collectively, these data indicate that HDAC6 contributes to the pathogenesis of rhabdomyolysis-induced AKI and suggest that HDAC6 inhibitors have therapeutic potential for AKI treatment. PMID:28052874

Inhibition of HDAC6 protects against rhabdomyolysis-induced acute kidney injury.

PubMed

Shi, Yingfeng; Xu, Liuqing; Tang, Jinhua; Fang, Lu; Ma, Shuchen; Ma, Xiaoyan; Nie, Jing; Pi, Xiaoling; Qiu, Andong; Zhuang, Shougang; Liu, Na

2017-03-01

Histone deacetylase 6 (HDAC6) inhibition has been reported to protect against ischemic stroke and prolong survival after sepsis in animal models. However, it remains unknown whether HDAC6 inhibition offers a renoprotective effect after acute kidney injury (AKI). In this study, we examined the effect of tubastatin A (TA), a highly selective inhibitor of HDAC6, on AKI in a murine model of glycerol (GL) injection-induced rhabdomyolysis. Following GL injection, the mice developed severe acute tubular injury as indicated by renal dysfunction; expression of neutrophil gelatinase-associated lipocalin (NGAL), an injury marker of renal tubules; and an increase of TdT-mediated dUTP nick-end labeling (TUNEL)-positive tubular cells. These changes were companied by increased HDAC6 expression in the cytoplasm of renal tubular cells. Administration of TA significantly reduced serum creatinine and blood urea nitrogen levels as well as attenuated renal tubular damage in injured kidneys. HDAC6 inhibition also resulted in decreased expression of NGAL, reduced apoptotic cell, and inactivated caspase-3 in the kidney after acute injury. Moreover, injury to the kidney increased phosphorylation of nuclear factor (NF)-κB and expression of multiple cytokines/chemokines including tumor necrotic factor-α and interleukin-6 and monocyte chemoattractant protein-1, as well as macrophage infiltration. Treatment with TA attenuated all those responses. Finally, HDAC6 inhibition reduced the level of oxidative stress by suppressing malondialdehyde (MDA) and preserving expression of superoxide dismutase (SOD) in the injured kidney. Collectively, these data indicate that HDAC6 contributes to the pathogenesis of rhabdomyolysis-induced AKI and suggest that HDAC6 inhibitors have therapeutic potential for AKI treatment. Copyright © 2017 the American Physiological Society.

Absence of chloride intracellular channel 4 (CLIC4) predisposes to acute kidney injury but has minimal impact on recovery

PubMed Central

2014-01-01

Background CLIC4, a member of the CLIC family of proteins, was recently demonstrated to translocate to the nucleus in differentiating keratinocytes where it potentiates TGFβ-driven gene regulation. Since TGFβ signaling is known to play important roles in the fibrotic response to acute kidney injury, and since CLIC4 is abundantly expressed in kidney, we hypothesized that CLIC4 may play a role in the response to acute kidney injury. Methods Previously described Clic4 null mice were analyzed for the effect of absence of CLIC4 on growth, development and response to kidney injury. Kidney size, glomerular counts and density of peritubular capillaries of matched WT and Clic4 null mice were determined. Cohorts of WT and Clic4 null mice were subjected to the folic acid model of acute kidney injury. Extent of acute injury and long term functional recovery were assessed by plasma blood urea nitrogen (BUN); long term fibrosis/scarring was determined by histochemical assessment of kidney sections and by residual renal mass. Activation of the TGFβ signaling pathway was assessed by semi-quantitative western blots of phosphorylated SMADs 2 and 3. Results CLIC4 is abundantly expressed in the apical pole of renal proximal tubule cells, and in endothelial cells of glomerular and peritubular capillaries. CLIC4 null mice are small, have smaller kidneys with fewer glomeruli and less dense peritubular capillary networks, and have increased proteinuria. The Clic4 null mice show increased susceptibility to folic acid-induced acute kidney injury but no difference in recovery from acute injury, no nuclear redistribution of CLIC4 following injury, and no significant difference in activation of the TGFβ-signaling pathway as reflected in the level of phosphorylation of SMADs 2 and 3. Conclusions Absence of CLIC4 results in morphologic changes consistent with its known role in angiogenesis. These changes may be at least partially responsible for the increased susceptibility to acute kidney

Treatment of acute lung injury by targeting MG53-mediated cell membrane repair

PubMed Central

Lieber, Gissela; Nishi, Miyuki; Yan, Rosalie; Wang, Zhen; Yao, Yonggang; Li, Yu; Whitson, Bryan A.; Duann, Pu; Li, Haichang; Zhou, Xinyu; Zhu, Hua; Takeshima, Hiroshi; Hunter, John C.; McLeod, Robbie L.; Weisleder, Noah; Zeng, Chunyu; Ma, Jianjie

2014-01-01

Injury to lung epithelial cells has a role in multiple lung diseases. We previously identified mitsugumin 53 (MG53) as a component of the cell membrane repair machinery in striated muscle cells. Here we show that MG53 also has a physiological role in the lung and may be used as a treatment in animal models of acute lung injury. Mice lacking MG53 show increased susceptibility to ischemia-reperfusion and over-ventilation induced injury to the lung when compared with wild type mice. Extracellular application of recombinant human MG53 (rhMG53) protein protects cultured lung epithelial cells against anoxia/reoxygenation-induced injuries. Intravenous delivery or inhalation of rhMG53 reduces symptoms in rodent models of acute lung injury and emphysema. Repetitive administration of rhMG53 improves pulmonary structure associated with chronic lung injury in mice. Our data indicate a physiological function for MG53 in the lung and suggest that targeting membrane repair may be an effective means for treatment or prevention of lung diseases. PMID:25034454

Pediatric Acute Kidney Injury.

PubMed

Fragasso, Tiziana; Ricci, Zaccaria; Goldstein, Stuart L

2018-01-01

Acute kidney injury (AKI) in children is a serious condition with an important impact on morbidity and mortality. Onset can be insidious and it is frequently unrecognized in the early phase when the therapeutic opportunities are theoretically more effective. The present review focuses on the most recent epidemiology studies and the progress in pediatric AKI (pAKI) research. Standardization of definition (presented in the Kidney Disease: Improving Global Outcomes) and novel biomarkers have been developed to help clinicians recognize kidney injury in a timely manner, both in adult and pediatric populations. Strengths and weaknesses of these diagnostic tools are discussed and the clinical scoring system (Renal Angina Index), which aims to provide a rational context for biomarker utilization, is also presented. Even if effective treatments are not currently available for established AKI, specific preventive approaches and some promising pharmacological treatments will be detailed. Renal replacement therapy is currently considered the most effective way to manage fluid balance when severe AKI occurs. Key Messages: Great efforts in pAKI research have today led to new strategies for early AKI detection and prevention strategies. Further studies have to be conducted in the next future in order to definitely improve the outcomes of pediatric patients experiencing this deadly syndrome. © 2018 S. Karger AG, Basel.

Molecular, Cellular and Functional Effects of Radiation-Induced Brain Injury: A Review

PubMed Central

Balentova, Sona; Adamkov, Marian

2015-01-01

Radiation therapy is the most effective non-surgical treatment of primary brain tumors and metastases. Preclinical studies have provided valuable insights into pathogenesis of radiation-induced injury to the central nervous system. Radiation-induced brain injury can damage neuronal, glial and vascular compartments of the brain and may lead to molecular, cellular and functional changes. Given its central role in memory and adult neurogenesis, the majority of studies have focused on the hippocampus. These findings suggested that hippocampal avoidance in cranial radiotherapy prevents radiation-induced cognitive impairment of patients. However, multiple rodent studies have shown that this problem is more complex. As the radiation-induced cognitive impairment reflects hippocampal and non-hippocampal compartments, it is of critical importance to investigate molecular, cellular and functional modifications in various brain regions as well as their integration at clinically relevant doses and schedules. We here provide a literature overview, including our previously published results, in order to support the translation of preclinical findings to clinical practice, and improve the physical and mental status of patients with brain tumors. PMID:26610477

Anti-RAGE antibody ameliorates severe thermal injury in rats through regulating cellular immune function

PubMed Central

Zhu, Xiao-mei; Yao, Yong-ming; Zhang, Li-tian; Dong, Ning; Yu, Yan; Sheng, Zhi-yong

2014-01-01

Aim: The receptor of advanced glycation end products (RAGE) participates in a variety of pathophysiological processes and inflammatory responses. The aim of this study was to investigate the therapeutic potential of an anti-RAGE neutralizing antibody for severe thermal injury in rats, and to determine whether the treatment worked via modulating cellular immune function. Methods: Full-thickness scald injury was induced in Wistar rats, which were treated with the anti-RAGE antibody (1 mg/kg, iv) at 6 h and 24 h after the injury. The rats were sacrificed on d 1, 3, 5, and 7. Blood and spleen samples were harvested to monitor organ function and to analyze dendritic cell (DC) and T cell cytokine profiles. The survival rate was analyzed up to d 7 after the injury. Results: Administration of the antibody significantly increased the 7 d survival rate in thermally injured rats (6.67% in the model group; 33.33% in anti-RAGE group). Treatment with the antibody also attenuated the multiple organ dysfunction syndrome (MODS) following the thermal injury, as shown by significant decreases in the organ dysfunction markers, including serum ALT, AST, blood urea nitrogen, creatinine and CK-MB. Moreover, treatment with the antibody significantly promoted DC maturation and T cell activation in the spleens of thermally injured rats. Conclusion: Blockade of the RAGE axis by the antibody effectively ameliorated MODS and improved the survival rate in thermally injured rats, which may be due to modulation of cellular immune function. PMID:25152026

A Systematic Review of the Outcomes of Posterolateral Corner Knee Injuries, Part 1: Surgical Treatment of Acute Injuries.

PubMed

Geeslin, Andrew G; Moulton, Samuel G; LaPrade, Robert F

2016-05-01

There is a paucity of outcome data to guide the surgical treatment of acute grade III posterolateral corner (PLC) knee injuries. To systematically review the literature to compare clinical outcomes of the treatment for acute grade III PLC injuries. Systematic review; Level of evidence, 4. A systematic review of the literature including Cochrane, PubMed, Medline, and Embase was performed. The following search terms were used: posterolateral corner knee, posterolateral knee, posterolateral instability, multiligament knee, and knee dislocation. Inclusion criteria were outcome studies of surgically treated acute PLC injuries with a minimum 2-year follow-up, subjective outcomes, objective outcomes including varus stability, and subgroup data on PLC injuries. Two investigators independently reviewed all abstracts. Accepted definitions of varus stability on examination or stress radiographs and the need for revision surgery were used to categorically define success and failure. Eight studies with a total of 134 patients were included. The mean patient age was reported in 7 studies (range, 21-31.5 years). The mean time to surgery was reported in 5 studies (range, 15-24.3 days); surgery was performed within 3 weeks in the other 3 studies. Four studies reported International Knee Documentation Committee scores (range, 78.1-91.3); 5 studies reported Lysholm scores (range, 87.5-90.3). Only 3 studies obtained bilateral varus stress radiographs. Based on an objective evaluation with varus stress examinations or radiographs, there was an overall success rate of 81% and failure rate of 19%. In 2 studies, the fibular collateral ligament and popliteus tendon were repaired and staged cruciate reconstruction performed in most patients; there were 17 failures of 45 patients (38%). In the remainder of the studies, patients were treated with local tissue transfer, hybrid repair for amenable structures or reconstruction for midsubstance tears, or reconstruction of all torn structures; the

Incidence and Risk Factors for Acute Kidney Injury Following Mannitol Infusion in Patients With Acute Stroke

PubMed Central

Lin, Shin-Yi; Tang, Sung-Chun; Tsai, Li-Kai; Yeh, Shin-Joe; Shen, Li-Jiuan; Wu, Fe-Lin Lin; Jeng, Jiann-Shing

2015-01-01

Abstract Mannitol, an osmotic diuretic, is commonly used to treat patients with acute brain edema, but its use also increases the risk of developing acute kidney injury (AKI). In this study, we investigated the incidence and risk factors of mannitol-related AKI in acute stroke patients. A total of 432 patients (ischemic stroke 62.3%) >20 years of age who were admitted to the neurocritical care center in a tertiary hospital and received mannitol treatment were enrolled in this study. Clinical parameters including the scores of National Institutes of Health Stroke Scale (NIHSS) at admission, vascular risk factors, laboratory data, and concurrent nephrotoxic medications were registered. Acute kidney injury was defined as an absolute elevation in the serum creatinine (Scr) level of ≥0.3 mg/dL from the baseline or a ≥50% increase in Scr. The incidence of mannitol-related AKI was 6.5% (95% confidence interval, 4.5%–9.3%) in acute stroke patients, 6.3% in patients with ischemic stroke, and 6.7% in patients with intracerebral hemorrhage. Multivariate analysis revealed that diabetes, lower estimated glomerular filtration rate at baseline, higher initial NIHSS score, and concurrent use of diuretics increased the risk of mannitol-related AKI. When present, the combination of these elements displayed an area under the receiver operating characteristic curve of 0.839 (95% confidence interval, 0.770–0.909). In conclusion, mannitol-related AKI is not uncommon in the treatment of acute stroke patients, especially in those with vulnerable risk factors. PMID:26632702

Shoe and Field Surface Risk Factors for Acute Lower Extremity Injuries Among Female Youth Soccer Players.

PubMed

OʼKane, John W; Gray, Kristen E; Levy, Marni R; Neradilek, Moni; Tencer, Allan F; Polissar, Nayak L; Schiff, Melissa A

2016-05-01

To describe acute lower extremity injuries and evaluate extrinsic risk factors in female youth soccer. Nested case-control study. Youth soccer clubs in Seattle, WA. Female soccer players (n = 351) ages 11 to 15 years randomly selected from 4 soccer clubs from which 83% of their players were enrolled with complete follow-up for 92% of players. Injured players were interviewed regarding injury, field surface, shoe type, and position. Uninjured controls, matched on game or practice session, were also interviewed. The association between risk factors and acute lower extremity injury using logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). One hundred seventy-three acute lower extremity injuries occurred involving primarily the ankle (39.3%), knee (24.9%), and thigh (11.0%). Over half (52.9%) recovered within 1 week, whereas 30.2% lasted beyond 2 weeks. During practices, those injured were approximately 3-fold (OR, 2.83; 95% CI, 1.49-5.31) more likely to play on grass than artificial turf and 2.4-fold (95% CI, 1.03-5.96) more likely to wear cleats on grass than other shoe and surface combinations. During games, injured players were 89% (95% CI, 1.03-4.17) more likely to play defender compared with forward. Half of the acute lower extremity injuries affected the ankle or knee. Grass surface and wearing cleats on grass increased training injuries. The majority, 64%, of female youth soccer players' acute injuries involve the ankle and knee and injury prevention strategies in this age group should target these areas. When considering playing surfaces for training, communities and soccer organizations should consider the third-generation artificial turf a safe alternative to grass.

Long-term remote organ consequences following acute kidney injury.

PubMed

Shiao, Chih-Chung; Wu, Pei-Chen; Huang, Tao-Min; Lai, Tai-Shuan; Yang, Wei-Shun; Wu, Che-Hsiung; Lai, Chun-Fu; Wu, Vin-Cent; Chu, Tzong-Shinn; Wu, Kwan-Dun

2015-12-28

Acute kidney injury (AKI) has been a global health epidemic problem with soaring incidence, increased long-term risks for multiple comorbidities and mortality, as well as elevated medical costs. Despite the improvement of patient outcomes following the advancements in preventive and therapeutic strategies, the mortality rates among critically ill patients with AKI remain as high as 40-60 %. The distant organ injury, a direct consequence of deleterious systemic effects, following AKI is an important explanation for this phenomenon. To date, most evidence of remote organ injury in AKI is obtained from animal models. Whereas the observations in humans are from a limited number of participants in a relatively short follow-up period, or just focusing on the cytokine levels rather than clinical solid outcomes. The remote organ injury is caused with four underlying mechanisms: (1) "classical" pattern of acute uremic state; (2) inflammatory nature of the injured kidneys; (3) modulating effect of AKI of the underlying disease process; and (4) healthcare dilemma. While cytokines/chemokines, leukocyte extravasation, oxidative stress, and certain channel dysregulation are the pathways involving in the remote organ damage. In the current review, we summarized the data from experimental studies to clinical outcome studies in the field of organ crosstalk following AKI. Further, the long-term consequences of distant organ-system, including liver, heart, brain, lung, gut, bone, immune system, and malignancy following AKI with temporary dialysis were reviewed and discussed.

In vivo imaging of spinal cord in contusion injury model mice by multi-photon microscopy

NASA Astrophysics Data System (ADS)

Oshima, Y.; Horiuchi, H.; Ogata, T.; Hikita, A.; Miura, H.; Imamura, T.

2014-03-01

Fluorescent imaging technique is a promising method and has been developed for in vivo applications in cellular biology. In particular, nonlinear optical imaging technique, multi-photon microscopy has make it possible to analyze deep portion of tissues in living animals such as axons of spinal code. Traumatic spinal cord injuries (SCIs) are usually caused by contusion damages. Therefore, observation of spinal cord tissue after the contusion injury is necessary for understanding cellular dynamics in response to traumatic SCI and development of the treatment for traumatic SCI. Our goal is elucidation of mechanism for degeneration of axons after contusion injuries by establishing SCI model and chronic observation of injured axons in the living animals. Firstly we generated and observed acute SCI model by contusion injury. By using a multi-photon microscope, axons in dorsal cord were visualized approximately 140 micron in depth from the surface. Immediately after injury, minimal morphological change of spinal cord was observed. At 3 days after injury, spinal cord was swelling and the axons seem to be fragmented. At 7 days after injury, increased degradation of axons could be observed, although the image was blurred due to accumulation of the connective tissue. In the present study, we successfully observed axon degeneration after the contusion SCI in a living animal in vivo. Our final goal is to understand molecular mechanisms and cellular dynamics in response to traumatic SCIs in acute and chronic stage.

Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents

PubMed Central

Eisenmann, Eric D.; Rorabaugh, Boyd R.; Zoladz, Phillip R.

2016-01-01

Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia–reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions. PMID:27199778

Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents.

PubMed

Eisenmann, Eric D; Rorabaugh, Boyd R; Zoladz, Phillip R

2016-01-01

Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia-reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions.

Acute Kidney Injury: Diagnostic Approaches and Controversies

PubMed Central

Makris, Konstantinos; Spanou, Loukia

2016-01-01

Acute kidney injury (AKI) is a significant independent risk factor for morbidity and mortality. In the last ten years a large number of publications have highlighted the limitations of traditional approaches and the inadequacies of conventional biomarkers to diagnose and monitor renal insufficiency in the acute setting. A great effort was directed not only to the discovery and validation of new biomarkers aimed to detect AKI more accurately but also to standardise the definition of AKI. Despite the advances in both areas, biomarkers have not yet entered into routine clinical practice and the definition of this syndrome has many areas of uncertainty. This review will discuss the controversies in diagnosis and the potential of novel biomarkers to improve the definition of the syndrome. PMID:28167845

Neuromuscular training with injury prevention counselling to decrease the risk of acute musculoskeletal injury in young men during military service: a population-based, randomised study

PubMed Central

2011-01-01

Background The rapidly increasing number of activity-induced musculoskeletal injuries among adolescents and young adults is currently a true public health burden. The objective of this study was to investigate whether a neuromuscular training programme with injury prevention counselling is effective in preventing acute musculoskeletal injuries in young men during military service. Methods The trial design was a population-based, randomised study. Two successive cohorts of male conscripts in four companies of one brigade in the Finnish Defence Forces were first followed prospectively for one 6-month term to determine the baseline incidence of injury. After this period, two new successive cohorts in the same four companies were randomised into two groups and followed prospectively for 6 months. Military service is compulsory for about 90% of 19-year-old Finnish men annually, who comprised the cohort in this study. This randomised, controlled trial included 968 conscripts comprising 501 conscripts in the intervention group and 467 conscripts in the control group. A neuromuscular training programme was used to enhance conscripts' motor skills and body control, and an educational injury prevention programme was used to increase knowledge and awareness of acute musculoskeletal injuries. The main outcome measures were acute injuries of the lower and upper limbs. Results In the intervention groups, the risk for acute ankle injury decreased significantly compared to control groups (adjusted hazards ratio (HR) = 0.34, 95% confidence interval (95% CI) = 0.15 to 0.78, P = 0.011). This risk decline was observed in conscripts with low as well as moderate to high baseline fitness levels. In the latter group of conscripts, the risk of upper-extremity injuries also decreased significantly (adjusted HR = 0.37, 95% CI 0.14 to 0.99, P = 0.047). In addition, the intervention groups tended to have less time loss due to injuries (adjusted HR = 0.55, 95% CI 0.29 to 1.04). Conclusions A

Neuromuscular training with injury prevention counselling to decrease the risk of acute musculoskeletal injury in young men during military service: a population-based, randomised study.

PubMed

Parkkari, Jari; Taanila, Henri; Suni, Jaana; Mattila, Ville M; Ohrankämmen, Olli; Vuorinen, Petteri; Kannus, Pekka; Pihlajamäki, Harri

2011-04-11

The rapidly increasing number of activity-induced musculoskeletal injuries among adolescents and young adults is currently a true public health burden. The objective of this study was to investigate whether a neuromuscular training programme with injury prevention counselling is effective in preventing acute musculoskeletal injuries in young men during military service. The trial design was a population-based, randomised study. Two successive cohorts of male conscripts in four companies of one brigade in the Finnish Defence Forces were first followed prospectively for one 6-month term to determine the baseline incidence of injury. After this period, two new successive cohorts in the same four companies were randomised into two groups and followed prospectively for 6 months. Military service is compulsory for about 90% of 19-year-old Finnish men annually, who comprised the cohort in this study. This randomised, controlled trial included 968 conscripts comprising 501 conscripts in the intervention group and 467 conscripts in the control group. A neuromuscular training programme was used to enhance conscripts' motor skills and body control, and an educational injury prevention programme was used to increase knowledge and awareness of acute musculoskeletal injuries. The main outcome measures were acute injuries of the lower and upper limbs. In the intervention groups, the risk for acute ankle injury decreased significantly compared to control groups (adjusted hazards ratio (HR) = 0.34, 95% confidence interval (95% CI) = 0.15 to 0.78, P = 0.011). This risk decline was observed in conscripts with low as well as moderate to high baseline fitness levels. In the latter group of conscripts, the risk of upper-extremity injuries also decreased significantly (adjusted HR = 0.37, 95% CI 0.14 to 0.99, P = 0.047). In addition, the intervention groups tended to have less time loss due to injuries (adjusted HR = 0.55, 95% CI 0.29 to 1.04). A neuromuscular training and injury

Targeting pro-inflammatory cytokines following joint injury: acute intra-articular inhibition of interleukin-1 following knee injury prevents post-traumatic arthritis

PubMed Central

2014-01-01

Introduction Post-traumatic arthritis (PTA) is a progressive, degenerative response to joint injury, such as articular fracture. The pro-inflammatory cytokines, interleukin 1(IL-1) and tumor necrosis factor alpha (TNF-α), are acutely elevated following joint injury and remain elevated for prolonged periods post-injury. To investigate the role of local and systemic inflammation in the development of post-traumatic arthritis, we targeted both the initial acute local inflammatory response and a prolonged 4 week systemic inflammatory response by inhibiting IL-1 or TNF-α following articular fracture in the mouse knee. Methods Anti-cytokine agents, IL-1 receptor antagonist (IL-1Ra) or soluble TNF receptor II (sTNFRII), were administered either locally via an acute intra-articular injection or systemically for a prolonged 4 week period following articular fracture of the knee in C57BL/6 mice. The severity of arthritis was then assessed at 8 weeks post-injury in joint tissues via histology and micro computed tomography, and systemic and local biomarkers were assessed in serum and synovial fluid. Results Intra-articular inhibition of IL-1 significantly reduced cartilage degeneration, synovial inflammation, and did not alter bone morphology following articular fracture. However, systemic inhibition of IL-1, and local or systemic inhibition of TNF provided no benefit or conversely led to increased arthritic changes in the joint tissues. Conclusion These results show that intra-articular IL-1, rather than TNF-α, plays a critical role in the acute inflammatory phase of joint injury and can be inhibited locally to reduce post-traumatic arthritis following a closed articular fracture. Targeted local inhibition of IL-1 following joint injury may represent a novel treatment option for PTA. PMID:24964765

ATF3 Protects Pulmonary Resident Cells from Acute and Ventilator-Induced Lung Injury by Preventing Nrf2 Degradation

PubMed Central

Shan, Yuexin; Akram, Ali; Amatullah, Hajera; Zhou, Dun Yuan; Gali, Patricia L.; Maron-Gutierrez, Tatiana; González-López, Adrian; Zhou, Louis; Rocco, Patricia R.M.; Hwang, David; Albaiceta, Guillermo M.; Haitsma, Jack J.

2015-01-01

Abstract Aims: Ventilator-induced lung injury (VILI) contributes to mortality in patients with acute respiratory distress syndrome, the most severe form of acute lung injury (ALI). Absence of activating transcription factor 3 (ATF3) confers susceptibility to ALI/VILI. To identify cell-specific ATF3-dependent mechanisms of susceptibility to ALI/VILI, we generated ATF3 chimera by adoptive bone marrow (BM) transfer and randomized to inhaled saline or lipopolysacharide (LPS) in the presence of mechanical ventilation (MV). Adenovirus vectors to silence or overexpress ATF3 were used in primary human bronchial epithelial cells and murine BM-derived macrophages from wild-type or ATF3-deficient mice. Results: Absence of ATF3 in myeloid-derived cells caused increased pulmonary cellular infiltration. In contrast, absence of ATF3 in parenchymal cells resulted in loss of alveolar-capillary membrane integrity and increased exudative edema. ATF3-deficient macrophages were unable to limit the expression of pro-inflammatory mediators. Knockdown of ATF3 in resident cells resulted in decreased junctional protein expression and increased paracellular leak. ATF3 overexpression abrogated LPS induced membrane permeability. Despite release of ATF3-dependent Nrf2 transcriptional inhibition, mice that lacked ATF3 expression in resident cells had increased Nrf2 protein degradation. Innovation: In our model, in the absence of ATF3 in parenchymal cells increased Nrf2 degradation is the result of increased Keap-1 expression and loss of DJ-1 (Parkinson disease [autosomal recessive, early onset] 7), previously not known to play a role in lung injury. Conclusion: Results suggest that ATF3 confers protection to lung injury by preventing inflammatory cell recruitment and barrier disruption in a cell-specific manner, opening novel opportunities for cell specific therapy for ALI/VILI. Antioxid. Redox Signal. 22, 651–668. PMID:25401197

Direct, indirect and intangible costs of acute hand and wrist injuries: A systematic review.

PubMed

Robinson, Luke Steven; Sarkies, Mitchell; Brown, Ted; O'Brien, Lisa

2016-12-01

Injuries sustained to the hand and wrist are common, accounting for 20% of all emergency presentations. The economic burden of these injuries, comprised of direct (medical expenses incurred), indirect (value of lost productivity) and intangible costs, can be extensive and rise sharply with the increase of severity. This paper systematically reviews cost-of-illness studies and health economic evaluations of acute hand and wrist injuries with a particular focus on direct, indirect and intangible costs. It aims to provide economic cost estimates of burden and discuss the cost components used in international literature. A search of cost-of-illness studies and health economic evaluations of acute hand and wrist injuries in various databases was conducted. Data extracted for each included study were: design, population, intervention, and estimates and measurement methodologies of direct, indirect and intangible costs. Reported costs were converted into US-dollars using historical exchange rates and then adjusted into 2015 US-dollars using an inflation calculator RESULTS: The search yielded 764 studies, of which 21 met the inclusion criteria. Twelve studies were cost-of-illness studies, and seven were health economic evaluations. The methodology used to derive direct, indirect and intangible costs differed markedly across all studies. Indirect costs represented a large portion of total cost in both cost-of-illness studies [64.5% (IQR 50.75-88.25)] and health economic evaluations [68% (IQR 49.25-73.5)]. The median total cost per case of all injury types was US$6951 (IQR $3357-$22,274) for cost-of-illness studies and US$8297 (IQR $3858-$33,939) for health economic evaluations. Few studies reported intangible cost data associated with acute hand and wrist injuries. Several studies have attempted to estimate the direct, indirect and intangible costs associated with acute hand and wrist injuries in various countries using heterogeneous methodologies. Estimates of the economic

Incidence and body location of reported acute sport injuries in seven sports using a national insurance database.

PubMed

Åman, M; Forssblad, M; Larsén, K

2018-03-01

Sports with high numbers of athletes and acute injuries are an important target for preventive actions at a national level. Both for the health of the athlete and to reduce costs associated with injury. The aim of this study was to identify injuries where injury prevention should focus, in order to have major impact on decreasing acute injury rates at a national level. All athletes in the seven investigated sport federations (automobile sports, basketball, floorball, football (soccer), handball, ice hockey, and motor sports) were insured by the same insurance company. Using this insurance database, the incidence and proportion of acute injuries, and injuries leading to permanent medical impairment (PMI), at each body location, was calculated. Comparisons were made between sports, sex, and age. In total, there were 84 754 registered injuries during the study period (year 2006-2013). Athletes in team sports, except in male ice hockey, had the highest risk to sustain an injury and PMI in the lower limb. Females had higher risk of injury and PMI in the lower limb compared to males, in all sports except in ice hockey. This study recommends that injury prevention at national level should particularly focus on lower limb injuries. In ice hockey and motor sports, head/neck and upper limb injuries also need attention. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparative Analysis of Liver Injury-Associated Cytokines in Acute Hepatitis A and B.

PubMed

Shin, So Youn; Jeong, Sook-Hyang; Sung, Pil Soo; Lee, Jino; Kim, Hyung Joon; Lee, Hyun Woong; Shin, Eui-Cheol

2016-05-01

Acute hepatitis A (AHA) and acute hepatitis B (AHB) are caused by an acute infection of the hepatitis A virus and the hepatitis B virus, respectively. In both AHA and AHB, liver injury is known to be mediated by immune cells and cytokines. In this study, we measured serum levels of various cytokines and T-cell cytotoxic proteins in patients with AHA or AHB to identify liver injury-associated cytokines. Forty-six patients with AHA, 16 patients with AHB, and 14 healthy adults were enrolled in the study. Serum levels of 17 cytokines and T-cell cytotoxic proteins were measured by enzyme-linked immunosorbent assays or cytometric bead arrays and analyzed for correlation with serum alanine aminotransferase (ALT) levels. Interleukin (IL)-18, IL-8, CXCL9, and CXCL10 were significantly elevated in both AHA and AHB. IL-6, IL-22, granzyme B, and soluble Fas ligand (sFasL) were elevated in AHA but not in AHB. In both AHA and AHB, the serum level of CXCL10 significantly correlated with the peak ALT level. Additionally, the serum level of granzyme B in AHA and the serum level of sFasL in AHB correlated with the peak ALT level. We identified cytokines and T-cell cytotoxic proteins associated with liver injury in AHA and AHB. These findings deepen the existing understanding of immunological mechanisms responsible for liver injury in acute viral hepatitis.

Comparative Analysis of Liver Injury-Associated Cytokines in Acute Hepatitis A and B

PubMed Central

Shin, So Youn; Jeong, Sook-Hyang; Sung, Pil Soo; Lee, Jino; Kim, Hyung Joon; Lee, Hyun Woong

2016-01-01

Purpose Acute hepatitis A (AHA) and acute hepatitis B (AHB) are caused by an acute infection of the hepatitis A virus and the hepatitis B virus, respectively. In both AHA and AHB, liver injury is known to be mediated by immune cells and cytokines. In this study, we measured serum levels of various cytokines and T-cell cytotoxic proteins in patients with AHA or AHB to identify liver injury-associated cytokines. Materials and Methods Forty-six patients with AHA, 16 patients with AHB, and 14 healthy adults were enrolled in the study. Serum levels of 17 cytokines and T-cell cytotoxic proteins were measured by enzyme-linked immunosorbent assays or cytometric bead arrays and analyzed for correlation with serum alanine aminotransferase (ALT) levels. Results Interleukin (IL)-18, IL-8, CXCL9, and CXCL10 were significantly elevated in both AHA and AHB. IL-6, IL-22, granzyme B, and soluble Fas ligand (sFasL) were elevated in AHA but not in AHB. In both AHA and AHB, the serum level of CXCL10 significantly correlated with the peak ALT level. Additionally, the serum level of granzyme B in AHA and the serum level of sFasL in AHB correlated with the peak ALT level. Conclusion We identified cytokines and T-cell cytotoxic proteins associated with liver injury in AHA and AHB. These findings deepen the existing understanding of immunological mechanisms responsible for liver injury in acute viral hepatitis. PMID:26996565

Rhabdomyolysis-Associated Acute Kidney Injury With Normal Creatine Phosphokinase.

PubMed

Kamal, Faisal; Snook, Lindsay; Saikumar, Jagannath H

2018-01-01

Rhabdomyolysis is a syndrome characterized by the breakdown of skeletal muscle and leakage of intracellular myocyte contents, such as creatine phosphokinase (CPK) and myoglobin, into the interstitial space and plasma resulting in acute kidney injury (AKI). Elevated CPK of at least 5 times the upper limit of normal is an important diagnostic marker of Rhabdomyolysis. We present a case of rhabdomyolysis with severe AKI with a normal CPK at presentation. A 32-year-old man presented with acute respiratory failure and AKI after an overdose of recreational drugs. Urinalysis at presentation showed trace amounts of blood, identified as rare red blood cells under microscopy. CPK was 156 U/L at presentation. Workup for glomerulonephritis and vasculitis was negative. He was initiated on renal replacement therapy, and a kidney biopsy showed severe acute tubular injury with positive myoglobin casts. Supportive management and renal replacement therapy was provided, and renal function spontaneously improved after a few weeks. This is an uncommon clinical presentation of severe rhabdomyolysis complicated by AKI. This suggests that CPK alone may not be a sensitive marker for rhabdomyolysis-induced AKI in some cases. Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

An 'injury-time integral' model for extrapolating from acute to chronic effects of phosgene.

PubMed

Hatch, G; Kodavanti, U; Crissman, K; Slade, R; Costa, D

2001-06-01

The present study compares acute and subchronic episodic exposures to phosgene to test the applicability of the 'concentrationxtime' (CxT) product as a measure of exposure dose, and to relate acute toxicity and adaptive responses to chronic toxicity. Rats (male Fischer 344) were exposed (six hours/day) to air or 0.1, 0.2, 0.5 and 1.0 ppm of phosgene one time or on a repeated regimen for up to 12 weeks as follows: 0.1 ppm (five days/week), 0.2 ppm (five days/week), 0.5 ppm (two days/week), or 1.0 ppm (one day/week) (note that the CxT for the three highest exposures was the same). Animals were sacrificed at 4, 8, and 12 weeks during the exposure and after four weeks recovery. Bronchoalveolar lavage (BAL) was performed 18 hours after the last exposure for each time period and the BAL supernatant assayed for protein. Elevated BAL fluid protein was defined as 'acute injury', diminished response after repeated exposure was defined as 'adaptation', and increased lung hydroxyproline or trichrome staining for collagen was defined as 'chronic injury'. Results indicated that exposures that cause maximal chronic injury involve high exposure concentrations and longer times between exposures, not high CxT products. A conceptual model is presented that explains the lack of CxT correlation by the fact that adaptation reduces an 'injury-time integral' as phosgene exposure is lengthened from acute to subchronic. At high exposure concentrations, the adaptive response appears to be overwhelmed, causing a continued injury-time integral, which appears to be related to appearance of chronic injury. The adaptive response is predicted to disappear if the time between exposures is lengthened, leading to a continued high injury-time integral and chronic injury. It has generally been assumed that long, continuous exposures of rodents is a conservative approach for detecting possible chronic effects. The present study suggests that such an approach my not be conservative, but might actually

Cellular mechanisms against ischemia reperfusion injury induced by the use of anesthetic pharmacological agents.

PubMed

Álvarez, P; Tapia, L; Mardones, L A; Pedemonte, J C; Farías, J G; Castillo, R L

2014-07-25

Ischemia-reperfusion (IR) cycle in the myocardium is associated with activation of an injurious cascade, thus leading to new myocardial challenges, which account for up to 50% of infarct size. Some evidence implicates reactive oxygen species (ROS) as a probable cause of myocardial injury in prooxidant clinical settings. Damage occurs during both ischemia and post-ischemic reperfusion in animal and human models. The mechanisms that contribute to this damage include the increase in cellular calcium (Ca(2+)) concentration and induction of ROS sources during reperfusion. Pharmacological preconditioning, which includes pharmacological strategies that counteract the ROS burst and Ca(2+) overload followed to IR cycle in the myocardium, could be effective in limiting injury. Currently widespread evidence supports the use of anesthetics agents as an important cardioprotective strategy that act at various levels such as metabotropic receptors, ion channels or mitochondrial level. Their administration before a prolonged ischemic episode is known as anesthetic preconditioning, whereas when given at the very onset of reperfusion, is termed anesthetic postconditioning. Both types of anesthetic conditioning reduce, albeit not to the same degree, the extent of myocardial injury. This review focuses on cellular and pathophysiological concepts on the myocardial damage induced by IR and how anesthetic pharmacological agents commonly used could attenuate the functional and structural effects induced by oxidative stress in cardiac tissue. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Cytoskeletal and morphologic impact of cellular oxidant injury.

PubMed Central

Hinshaw, D. B.; Sklar, L. A.; Bohl, B.; Schraufstatter, I. U.; Hyslop, P. A.; Rossi, M. W.; Spragg, R. G.; Cochrane, C. G.

1986-01-01

The relationship between changes in cell morphology and the cytoskeleton in oxidant injury was examined in the P388D1 cell line. Flow cytometry of cells stained with NBD-phallacidin, a fluorescent probe specific for filamentous (F) actin, revealed a substantial increase in F actin content in H2O2-injured cells over 3-4 hours. Doses of H2O2 as low as 500 microM produced sustained increases in F actin content. Experiments where catalase was used to interrupt H2O2 exposure over a long time course revealed 15-30 minutes to be the critical period of exposure to 5 mM H2O2 necessary for a sustained increase in F actin as well as large increases in membrane blebbing and later cell death. The increase in F actin with H2O2 injury was confirmed with the use of electrophoresis in acrylamide gels of 1% Triton X-100 cytoskeletal extracts from P388D1 cells. Scanning electron microscopy revealed major loss of surface convolutions in addition to the formation of blebs. Fluorescence microscopy of adherent cells using rhodamine phalloidin showed considerable cell rounding and rearrangement of cellular F actin by 30 minutes of exposure to H2O2. Transmission electron microscopy revealed side to side aggregation of F actin bundles (microfilaments) developing during this time. Considerable swelling of mitochondria and other subcellular organelles was seen after 2 hours of injury. The apparent area of attachment to the substrate was markedly diminished in injured cells. H2O2 injury produced a marked increase in F actin with an associated rearrangement of the microfilaments and simultaneous changes in the plasma membrane prior to cell death in the P388D1 cell line. Images Figure 5 Figure 6 Figure 7 Figure 8 PMID:3717299

Cellular Therapies for Treatment of Radiation Injury: Report from a NIH/NIAID and IRSN Workshop

PubMed Central

DiCarlo, Andrea L.; Tamarat, Radia; Rios, Carmen I.; Benderitter, Marc; Czarniecki, Christine W.; Allio, Theresa C.; Macchiarini, Francesca; Maidment, Bert W.; Jourdain, Jean-Rene

2017-01-01

In recent years, there has been increasing concern over the possibility of a radiological or nuclear incident occurring somewhere in the world. Intelligence agencies frequently report that terrorist groups and rogue nations are seeking to obtain radiological or nuclear weapons of mass destruction. In addition, there exists the real possibility that safety of nuclear power reactors could be compromised by natural (such as the tsunami and subsequent Fukushima accident in Japan in March, 2011) or accidental (Three Mile Island, 1979 and Chernobyl, 1986) events. Although progress has been made by governments around the world to prepare for these events, including the stockpiling of radiation countermeasures, there are still challenges concerning care of patients injured during a radiation incident. Because the deleterious and pathological effects of radiation are so broad, it is desirable to identify medical countermeasures that can have a beneficial impact on several tissues and organ systems. Cellular therapies have the potential to impact recovery and tissue/organ regeneration for both early and late complications of radiation exposure. These therapies, which could include stem or blood progenitor cells, mesenchymal stromal cells (MSCs) or cells derived from other tissues (e.g., endothelium or placenta), have shown great promise in treating other nonradiation injuries to and diseases of the bone marrow, skin, gastrointestinal tract, brain, lung and heart. To explore the potential use of these therapies in the treatment of victims after acute radiation exposure, the National Institute of Allergy and Infectious Diseases cosponsored an international workshop in July, 2015 in Paris, France with the Institut de Radioprotection et de Sûreté Nucléaire. The workshop included discussions of data available from testing in preclinical models of radiation injury to different organs, logistics associated with the practical use of cellular therapies for a mass casualty incident

Adoptive transfer of acute lung injury.

PubMed

Moxley, M A; Baird, T L; Corbett, J A

2000-11-01

In this study, we describe a novel adoptive transfer protocol to study acute lung injury in the rat. We show that bronchoalveolar lavage (BAL) cells isolated from rats 5 h after intratracheal administration of lipopolysaccharide (LPS) induce a lung injury when transferred to normal control recipient rats. This lung injury is characterized by increased alveolar-arterial oxygen difference and extravasation of Evans blue dye (EBD) into lungs of recipient rats. Recipient rats receiving similar numbers of donor cells isolated from healthy rats do not show adverse changes in the alveolar-arterial oxygen difference or in extravasation of EBD. The adoptive transfer-induced lung injury is associated with increased numbers of neutrophils in the BAL, the levels of which are similar to the numbers observed in BAL cells isolated from rats treated for 5 h with LPS. As an indicator of BAL cell activation, donor BAL cell inducible nitric oxide synthase (iNOS) expression was compared with BAL cell iNOS expression 48 h after adoptive transfer. BAL cells isolated 5 h after LPS administration expressed iNOS immediately after isolation. In contrast, BAL cells isolated 48 h after adoptive transfer did not express iNOS immediately after isolation but expressed iNOS following a 24-h ex vivo culture. These findings indicate that the activation state of donor BAL cells differs from BAL cells isolated 48 h after adoptive transfer, suggesting that donor BAL cells may stimulate migration of new inflammatory cells into the recipient rats lungs.

How do I manage an acute injury to the facial nerve?

PubMed

Colbert, Serryth; Coombes, Daryl; Godden, Daryl; Cascarini, Luke; Kerawala, Cyrus; Brennan, Peter A

2014-01-01

Paralysis of the facial nerve is a cause of considerable functional and aesthetic disfigurement. Damage to the upper trunk can result in eye complications with the risk of exposure keratitis. Numerous factors influence the therapeutic strategy: the cause of the injury, the time elapsed since injury, functional impairment, and the likelihood of recovery. We discuss the management of an acute injury to the facial nerve and focus on the surgical options. Copyright © 2013 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Simulation of Changes in Diffusion Related to Different Pathologies at Cellular Level After Traumatic Brain Injury

PubMed Central

Lin, Mu; He, Hongjian; Schifitto, Giovanni; Zhong, Jianhui

2016-01-01

Purpose The goal of the current study was to investigate tissue pathology at the cellular level in traumatic brain injury (TBI) as revealed by Monte Carlo simulation of diffusion tensor imaging (DTI)-derived parameters and elucidate the possible sources of conflicting findings of DTI abnormalities as reported in the TBI literature. Methods A model with three compartments separated by permeable membranes was employed to represent the diffusion environment of water molecules in brain white matter. The dynamic diffusion process was simulated with a Monte Carlo method using adjustable parameters of intra-axonal diffusivity, axon separation, glial cell volume fraction, and myelin sheath permeability. The effects of tissue pathology on DTI parameters were investigated by adjusting the parameters of the model corresponding to different stages of brain injury. Results The results suggest that the model is appropriate and the DTI-derived parameters simulate the predominant cellular pathology after TBI. Our results further indicate that when edema is not prevalent, axial and radial diffusivity have better sensitivity to axonal injury and demyelination than other DTI parameters. Conclusion DTI is a promising biomarker to detect and stage tissue injury after TBI. The observed inconsistencies among previous studies are likely due to scanning at different stages of tissue injury after TBI. PMID:26256558

Rapid Rule-Out of Acute Myocardial Injury Using a Single High-Sensitivity Cardiac Troponin I Measurement.

PubMed

Sandoval, Yader; Smith, Stephen W; Shah, Anoop S V; Anand, Atul; Chapman, Andrew R; Love, Sara A; Schulz, Karen; Cao, Jing; Mills, Nicholas L; Apple, Fred S

2017-01-01

Rapid rule-out strategies using high-sensitivity cardiac troponin assays are largely supported by studies performed outside the US in selected cohorts of patients with chest pain that are atypical of US practice, and focused exclusively on ruling out acute myocardial infarction (AMI), rather than acute myocardial injury, which is more common and associated with a poor prognosis. Prospective, observational study of consecutive patients presenting to emergency departments [derivation (n = 1647) and validation (n = 2198) cohorts], where high-sensitivity cardiac troponin I (hs-cTnI) was measured on clinical indication. The negative predictive value (NPV) and diagnostic sensitivity of an hs-cTnI concentration acute myocardial injury and for AMI or cardiac death at 30 days. In patients with hs-cTnI concentrations <99th percentile at presentation, acute myocardial injury occurred in 8.3% and 11.0% in the derivation and validation cohorts, respectively. In the derivation cohort, 27% had hs-cTnI < LoD, with NPV and diagnostic sensitivity for acute myocardial injury of 99.1% (95% CI, 97.7-99.8) and 99.0% (97.5-99.7) and an NPV for AMI or cardiac death at 30 days of 99.6% (98.4-100). In the validation cohort, 22% had hs-cTnI acute myocardial injury of 98.8% (97.9-99.7) and 99.3% (98.7-99.8) and an NPV for AMI or cardiac death at 30 days of 99.1% (98.2-99.8). A single hs-cTnI concentration acute myocardial injury, regardless of etiology, with an excellent NPV and diagnostic sensitivity, and identifies patients at minimal risk of AMI or cardiac death at 30 days. ClinicalTrials.gov Identifier: NCT02060760. © 2016 American Association for Clinical Chemistry.

Epidemiology and Outcome of Acute Kidney Injury According to Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease and Kidney Disease: Improving Global Outcomes Criteria in Critically Ill Children-A Prospective Study.

PubMed

Volpon, Leila C; Sugo, Edward K; Consulin, Julio C; Tavares, Tabata L G; Aragon, Davi C; Carlotti, Ana P C P

2016-05-01

We aimed to investigate the epidemiology, risk factors, and short- and medium-term outcome of acute kidney injury classified according to pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease, and Kidney Disease: Improving Global Outcomes criteria in critically ill children. Prospective observational cohort study. Two eight-bed PICUs of a tertiary-care university hospital. A heterogeneous population of critically ill children. None. Demographic, clinical, laboratory, and outcome data were collected on all patients admitted to the PICUs from August 2011 to January 2012, with at least 24 hours of PICU stay. Of the 214 consecutive admissions, 160 were analyzed. The prevalence of acute kidney injury according to pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease and Kidney Disease: Improving Global Outcomes criteria was 49.4% vs. 46.2%, respectively. A larger proportion of acute kidney injury episodes was categorized as Kidney Disease: Improving Global Outcomes stage 3 (50%) compared with pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease F (39.2%). Inotropic score greater than 10 was a risk factor for acute kidney injury severity. About 35% of patients with acute kidney injury who survived were discharged from the PICU with an estimated creatinine clearance less than 75 mL/min/1.73 m and one persisted with altered renal function 6 months after PICU discharge. Age 12 months old or younger was a risk factor for estimated creatinine clearance less than 75 mL/min/1.73 m at PICU discharge. Acute kidney injury and its severity were associated with increased PICU length of stay and longer duration of mechanical ventilation. Eleven patients died; nine had acute kidney injury (p < 0.05). The only risk factor associated with death after multivariate adjustment was Pediatric Risk of Mortality score greater than or equal to 10. Acute kidney injury defined by both pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease and Kidney Disease

Contrast-induced acute kidney injury: potential new strategies.

PubMed

Briguori, Carlo; Donnarumma, Elvira; Quintavalle, Cristina; Fiore, Danilo; Condorelli, Gerolama

2015-03-01

Contrast-induced acute kidney injury (CI-AKI) is an impairment of renal function following contrast media administration in the absence of an alternative cause. It represents a powerful predictor of poor early and late outcomes. Here, we review the major strategies to prevent CI-AKI. Hydration represents the gold standard as a prophylactic measure to prevent CI-AKI, acting by increasing urine flow rate and, thereby, by limiting the time of contact between the contrast media and the tubular epithelial cells. An optimal hydration regimen should be defined according to predefined clinical markers, such as urine flow rate, or left ventricular end-diastolic pressure. Recently, high-dose statins pretreatment has been included in the guidelines of CI-AKI prevention. However, uncertainty still exists on the efficacy of several compounds tested in both observational trials and randomized studies to prevent CI-AKI. Compounds evaluated include diuretics (furosemide), antioxidants (i.e. N-acetylcysteine and statins) and vasodilators (i.e. calcium antagonists, dopamine and fenoldopam). Hydration still represents the most reliable strategy to prevent CI-AKI. New prophylactic strategies for acute kidney injury are still under investigation.

Mechanisms of alveolar fibrosis after acute lung injury.

PubMed

Marinelli, W A; Henke, C A; Harmon, K R; Hertz, M I; Bitterman, P B

1990-12-01

In patients who die after severe acute lung injury, a dramatic fibroproliferative response occurs within the alveolar air space, interstitium, and microvessels. Profound shunt physiology, dead space ventilation, and pulmonary hypertension are the physiologic consequences of this fibroproliferative response. The anatomic pattern of the response is unique within each alveolar compartment. For example, the air space is obliterated by granulation tissue, with replicating mesenchymal cells, their connective tissue products, and an expanding network of intra-alveolar capillaries. In contrast, the vascular fibroproliferative response is dominated by mesenchymal cell replication and connective tissue deposition within the walls of microvessels. Despite the unique anatomic features of these fibroproliferative processes, the regulatory signals involved are likely to be similar. Although our current understanding of the signals regulating the fibroproliferative response to acute lung injury is limited, inferences can be made from in vitro studies of mesenchymal cell behavior and several better understood fibroproliferative processes, including wound healing and chronic fibrotic lung diseases. As clinicians, our future ability to enhance effective lung repair will likely utilize therapeutic strategies specifically targeted to the signals that regulate the fibroproliferative process within the alveolar microenvironment.

Renal angina: concept and development of pretest probability assessment in acute kidney injury.

PubMed

Chawla, Lakhmir S; Goldstein, Stuart L; Kellum, John A; Ronco, Claudio

2015-02-27

The context of a diagnostic test is a critical component for the interpretation of its result. This context defines the pretest probability of the diagnosis and forms the basis for the interpretation and value of adding the diagnostic test. In the field of acute kidney injury, a multitude of early diagnostic biomarkers have been developed, but utilization in the appropriate context is less well understood and has not been codified until recently. In order to better operationalize the context and pretest probability assessment for acute kidney injury diagnosis, the renal angina concept was proposed in 2010 for use in both children and adults. Renal angina has been assessed in approximately 1,000 subjects. However, renal angina as a concept is still unfamiliar to most clinicians and the rationale for introducing the term is not obvious. We therefore review the concept and development of renal angina, and the currently available data validating it. We discuss the various arguments for and against this construct. Future research testing the performance of renal angina with acute kidney injury biomarkers is warranted.

Neuroprotective effects of autophagy induced by rapamycin in rat acute spinal cord injury model.

PubMed

Wang, Zhen-Yu; Liu, Wen-Ge; Muharram, Akram; Wu, Zhao-Yan; Lin, Jian-Hua

2014-01-01

To explore the effects of rapamycin-induced autophagy on apoptosis in a rat model of acute spinal cord injury (SCI), and to explore the effect of rapamycin on apoptosis in primary spinal cord cell culture. SCI was induced at T10 in female adult Sprague-Dawley rats. After injury was induced, the rats were injected with rapamycin and/or methylprednisolone and were sacrificed at various days after injury. Apoptosis and autophagy were examined with TUNEL staining and electron microscopy. Hind limb function was assessed by the Gale scale. The expression of the apoptosis-related protein caspase-3 did not significantly increase until 21 days following injury, while increases in LC3II and LC3I began 10 days after injury, but then declined. TUNEL staining and electron microscopy confirmed that following injury autophagy occurred before apoptosis, but by 14 days after the injury, the level of autophagy had decreased significantly while the level of apoptosis showed a continued increase. Following treatment with rapamycin, apoptosis was significantly higher than in the vehicle control group, but significantly lower than in the sham-operated group, showing a protective effect of rapamycin. Gale scale grades in rats treated with rapamycin were significantly higher compared with the vehicle control group, suggesting a functional effect of rapamycin-induced inhibition of apoptosis. The results indicate that rapamycin significantly improved the prognosis of acute SCI in rats by inhibiting cell apoptosis. Rapamycin might be useful as a therapeutic agent for acute SCI. © 2014 S. Karger AG, Basel

Zymogen proteolysis within the pancreatic acinar cell is associated with cellular injury.

PubMed

Grady, T; Mah'Moud, M; Otani, T; Rhee, S; Lerch, M M; Gorelick, F S

1998-11-01

The pathological activation of digestive zymogens within the pancreatic acinar cell probably plays a central role in initiating many forms of pancreatitis. To examine the relationship between zymogen activation and acinar cell injury, we investigated the effects of secretagogue treatment on isolated pancreatic acini. Immunofluorescence studies using antibodies to the trypsinogen-activation peptide demonstrated that both CCK (10(-7) M) hyperstimulation and bombesin (10(-5) M) stimulation of isolated acini resulted in trypsinogen processing to trypsin. These treatments also induced the proteolytic processing of procarboxypeptidase A1 to carboxypeptidase A1 (CA1). After CCK hyperstimulation, most CA1 remained in the acinar cell. In contrast, the CA1 generated by bombesin was released from the acinar cell. CCK hyperstimulation of acini was associated with cellular injury, whereas bombesin treatment did not induce injury. These studies suggest that 1) proteolytic zymogen processing occurs within the pancreatic acinar cell and 2) both zymogen activation and the retention of enzymes within the acinar cell may be required to induce injury.

Quantification of vascular damage in acute kidney injury with fluorine magnetic resonance imaging and spectroscopy.

PubMed

Moore, Jeremy K; Chen, Junjie; Pan, Hua; Gaut, Joseph P; Jain, Sanjay; Wickline, Samuel A

2018-06-01

To design a fluorine MRI/MR spectroscopy approach to quantify renal vascular damage after ischemia-reperfusion injury, and the therapeutic response to antithrombin nanoparticles (NPs) to protect kidney function. A total of 53 rats underwent 45 min of bilateral renal artery occlusion and were treated at reperfusion with either plain perfluorocarbon NPs or NPs functionalized with a direct thrombin inhibitor (PPACK:phenyalanine-proline-arginine-chloromethylketone). Three hours after reperfusion, kidneys underwent ex vivo fluorine MRI/MR spectroscopy at 4.7 T to quantify the extent and volume of trapped NPs, as an index of vascular damage and ischemia-reperfusion injury. Microscopic evaluation of structural damage and NP trapping in non-reperfused renal segments was performed. Serum creatinine was quantified serially over 7 days. The damaged renal cortico-medullary junction trapped a significant volume of NPs (P = 0.04), which correlated linearly (r = 0.64) with the severity of kidney injury 3 h after reperfusion. Despite global large vessel reperfusion, non-reperfusion in medullary peritubular capillaries was confirmed by MRI and microscopy, indicative of continuing hypoxia due to vascular compromise. Treatment of animals with PPACK NPs after acute kidney injury did not accelerate kidney functional recovery. Quantification of ischemia-reperfusion injury after acute kidney injury with fluorine MRI/MR spectroscopy of perfluorocarbon NPs objectively depicts the extent and severity of vascular injury and its linear relationship to renal dysfunction. The lack of kidney function improvement after early posttreatment thrombin inhibition confirms the rapid onset of ischemia-reperfusion injury as a consequence of vascular damage and non-reperfusion. The prolongation of medullary ischemia renders cortico-medullary tubular structures susceptible to continued necrosis despite restoration of large vessel flow, which suggests limitations to acute interventions after

Preventive Effects of Eccentric Training on Acute Hamstring Muscle Injury in Professional Baseball

PubMed Central

Seagrave, Richard A.; Perez, Luis; McQueeney, Sean; Toby, E. Bruce; Key, Vincent; Nelson, Joshua D.

2014-01-01

Background: Hamstring injuries are the second most common injury causing missed days in professional baseball field players. Recent studies have shown the preventive benefit of eccentric conditioning on the hamstring muscle group in injury prevention. Specifically, Nordic-type exercises have been shown to decrease the incidence of acute hamstring injuries in professional athletes. Purpose: This was a prospective study performed in coordination with a single Major League Baseball (MLB) organization (major and minor league teams) that targeted the effects of Nordic exercises on the incidence of acute hamstring injuries in the professional-level baseball player. Study Design: Prospective cohort study; Level of evidence, 2. Methods: The daily workouts of 283 professional baseball players throughout all levels of a single MLB organization were prospectively recorded. The intervention group participated in the Nordic exercise program and was compared with a randomly selected control group of professional athletes within the organization not participating in the exercise program. The incidence of hamstring injuries in both groups was compared, and the total number of days missed due to injury was compared with the 2 previous seasons. Results: There were 10 hamstring injuries that occurred during the 2012 season among the 283 professional athletes that required removal from play. There were no injuries that occurred in the intervention group (n = 65, 0.00%; P = .0381). The number needed to treat (NNT) to prevent 1 hamstring injury was 11.3. The average repetitions per week of the injured group were assessed at multiple time points (2, 4, 6, and total weeks) prior to injury. There were significantly fewer repetitions per week performed in the injured group at all time points compared with overall average repetitions per week in the noninjured group (P = .0459, .0127, .0164, and .0299, respectively). After beginning the Nordic exercise program, there were 136 total days

Citral inhibits lipopolysaccharide-induced acute lung injury by activating PPAR-γ.

PubMed

Shen, Yongbin; Sun, Zhanfeng; Guo, Xiaotong

2015-01-15

Citral, a component of lemongrass oil, has been reported to have many pharmacological activities such as anti-bacterial and anti-inflammatory effects. However, the effects of citral on acute lung injury (ALI) and the molecular mechanisms have not been reported. The aim of this study was to detect the effects of citral on lipopolysaccharide (LPS)-induced acute lung injury and investigate the molecular mechanisms. LPS-induced acute lung injury model was used to detect the anti-inflammatory effect of citral in vivo. The alveolar macrophages were used to investigate the molecular mechanism of citral in vitro. The results showed that pretreatment with citral remarkably attenuated pulmonary edema, histological severities, TNF-α, IL-6 and IL-1β production in LPS-induced ALI in vivo. In vitro, citral inhibited LPS-induced TNF-α, IL-6 and IL-1β production in alveolar macrophages. LPS-induced NF-κB activation was also inhibited by citral. Furthermore, we found that citral activated PPAR-γ and the anti-inflammatory effects of citral can be reversed by PPAR-γ antagonist GW9662. In conclusion, this is the first to demonstrate that citral protects LPS-induced ALI in mice. The anti-inflammatory mechanism of citral is associated with activating PPAR-γ, thereby inhibiting LPS-induced inflammatory response. Copyright © 2014 Elsevier B.V. All rights reserved.

Mild traumatic brain injury in children: management practices in the acute care setting.

PubMed

Kool, Bridget; King, Vivienne; Chelimo, Carol; Dalziel, Stuart; Shepherd, Michael; Neutze, Jocelyn; Chambers, Nikki; Wells, Susan

2014-08-01

Accurate diagnosis, treatment and follow up of children suffering mild traumatic brain injury (MTBI) is important as post-concussive symptoms and long-term disability might occur. This research explored the decisions clinicians make in their assessment and management of children with MTBI in acute care settings, and identified barriers and enablers to the delivery of best-practice care. A purposeful sample of 29 clinicians employed in two metropolitan paediatric EDs and one Urgent Care clinic was surveyed using a vignette-based questionnaire that also included domains of guideline awareness, attitudes to MTBI care, use of clinical decision support systems, and knowledge and skills for practising evidence-based healthcare. Overall, the evaluation and management of children presenting acutely with MTBI generally followed best-practice guidelines, particularly in relation to identifying intracranial injuries that might require surgical intervention, observation for potential deterioration, adequate pain management and the provision of written head injury advice on discharge. Larger variation emerged in regard to follow-up care and referral pathways. Potential barriers to best- practice were lack of guideline awareness, attitudes to MTBI, and lack of time or other priorities. Opportunities exist to improve care for children who present in acute care settings following mild traumatic brain injury. These include having up-to-date guidelines that are consistent across acute care settings; providing clearer pathways for referral and follow up; targeting continuing medical education towards potential complications; and providing computerised decision support so that assessment and management are conducted systematically. © 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Irisin-mediated protective effect on LPS-induced acute lung injury via suppressing inflammation and apoptosis of alveolar epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shao, Lei; Jinan Central Hospital Affiliated to Shandong University, Jinan 250012; Meng, Di

It is considered that the essence of acute lung injury (ALI) is an excessive and uncontrolled inflammatory response in lung, of which mainly is attributed to the release of inflammatory mediators. Recent studies demonstrated that irisin, which is a metabolism associated factor after physical exercise could suppression of inflammation by regulating cellular signaling pathways, however, the underlying molecular mechanism remains to be determined. The present study aimed to reveal the potential mechanism responsible for the anti-inflammatory effects of irisin on LPS-induced acute lung injury in mice and in A549 cells. The results of histopathological changes showed that irisin ameliorated the lungmore » injury that was induced by LPS in time- and dose-dependent manner. QRT-PCR assays demonstrated that irisin suppressed the production of IL-1β, IL-6, MCP-1 and TNF-α, and western blot assays demonstrated that irisin suppressed apoptosis of ALI. The expression of caspase-3 and Bax were decreased and Bcl-2 was increased by irisin administration. Further study was conducted on nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) using pathways using western blots. The results showed that irisin inhibited reduced LPS-induced activation of MAPK and NF-κB signaling. All results indicated that irisin has protective effect on LPS-induced ALI in mice and in A549 cells. Thus, irisn related with physical exercise may be a potential therapy for the treatment of pulmonary inflammation. - Highlights: • Irisin inhibited the inflammation reactivity of cells and pathological changes of LPS-induced lung injury in mice. • Irisin inhibited mRNA expression of inflammatory cytokines induced by LPS in A549 cells. • Irisin inhibited apoptosis induced by LPS in the injured lung. • Irisin reduced LPS-induced activation of MAPK and NF-κB signaling pathways.« less

Synthetic marijuana and acute kidney injury: an unforeseen association.

PubMed

Kazory, Amir; Aiyer, Ravi

2013-06-01

Synthetic cannabinoids (SCs) have emerged as drugs of abuse with increasing popularity among young adults. The potential renal complication related to the abuse of SC was not recognized until recently. Here, we present a case of severe acute kidney injury (AKI) that developed after inhalation of SC in an otherwise healthy young patient. A kidney biopsy revealed severe acute tubular necrosis, and supportive management resulted in the recovery of the kidney function. Herein, we briefly summarize the only two previous reports (a total of 21 cases) on the association between SC abuse and renal dysfunction and identify the common aspects in all observations.

Shoe and field surface risk factors for acute lower extremity injuries among female youth soccer players

PubMed Central

O'Kane, John W.; Gray, Kristen E.; Levy, Marni R.; Neradilek, Moni; Tencer, Allan F.; Polissar, Nayak L.; Schiff, Melissa A.

2015-01-01

Objective Describe acute lower extremity injuries and evaluate extrinsic risk factors in female youth soccer Design Nested case-control study Setting Youth soccer clubs in Washington State, USA. Participants Female soccer players (N= 351) ages 11 to 15 years randomly selected from 4 soccer clubs from which 83% of their players were enrolled with complete follow-up for 92% of players. Interventions Injured players were interviewed regarding injury, field surface, shoe type, and position. Uninjured controls, matched on game or practice session, were also interviewed. Main Outcome Measures The association between risk factors and acute lower extremity injury using logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). Results One hundred seventy-three acute lower extremity injuries occurred involving primarily the ankle (39.3%), knee (24.9%), and thigh (11.0%). Over half (52.9%) recovered within 1 week, while 30.2% lasted beyond 2 weeks. During practices, those injured were approximately 3-fold ( OR 2.83, 95% CI 1.49-5.31) more likely to play on grass than artificial turf and 2.4-fold (95% CI 1.03-5.96) more likely to wear cleats on grass than other shoe and surface combinations. During games injured players were 89% (95% CI 1.03-4.17) more likely to play defender compared to forward. Conclusions Half of the acute lower extremity injuries affected the ankle or knee. Grass surface and wearing cleats on grass increased training injuries. PMID:26327288

The developing oligodendrocyte: key cellular target in brain injury in the premature infant

PubMed Central

Volpe, Joseph J.; Kinney, Hannah C.; Jensen, Frances, E.; Rosenberg, Paul A.

2011-01-01

Brain injury in the premature infant, a problem of enormous importance, is associated with a high risk of neurodevelopmental disability. The major type of injury involves cerebral white matter and the principal cellular target is the developing oligodendrocyte. The specific phase of the oligodendroglial lineage affected has been defined from study of both human brain and experimental models. This premyelinating cell (pre-OL) is vulnerable because of a series of maturation-dependent events. The pathogenesis of pre-OL injury relates to operation of two upstream mechanisms, hypoxia-ischemia and systemic infection/inflammation, both of which are common occurrences in premature infants. The focus of this review and of our research over the past 15-20 years has been the cellular and molecular bases for the maturation-dependent vulnerability of the pre-OL to the action of the two upstream mechanisms. Three downstream mechanisms have been identified, i.e., microglial activation, excitotoxicity and free radical attack. The work in both experimental models and human brain has identified a remarkable confluence of maturation-dependent factors that render the pre-OL so exquisitely vulnerable to these downstream mechanisms. Most importantly, elucidation of these factors has led to delineation of a series of potential therapeutic interventions, which in experimental models show marked protective properties. The critical next step, i.e., clinical trials in the living infant, is now on the horizon. PMID:21382469

Impact of real-time electronic alerting of acute kidney injury on therapeutic intervention and progression of RIFLE class.

PubMed

Colpaert, Kirsten; Hoste, Eric A; Steurbaut, Kristof; Benoit, Dominique; Van Hoecke, Sofie; De Turck, Filip; Decruyenaere, Johan

2012-04-01

To evaluate whether a real-time electronic alert system or "AKI sniffer," which is based on the RIFLE classification criteria (Risk, Injury and Failure), would have an impact on therapeutic interventions and acute kidney injury progression. Prospective intervention study. Surgical and medical intensive care unit in a tertiary care hospital. A total of 951 patients having in total 1,079 admission episodes were admitted during the study period (prealert control group: 227, alert group: 616, and postalert control group: 236). Three study phases were compared: A 1.5-month prealert control phase in which physicians were blinded for the acute kidney injury sniffer and a 3-month intervention phase with real-time alerting of worsening RIFLE class through the Digital Enhanced Cordless Technology telephone system followed by a second 1.5-month postalert control phase. A total of 2593 acute kidney injury alerts were recorded with a balanced distribution over all study phases. Most acute kidney injury alerts were RIFLE class risk (59.8%) followed by RIFLE class injury (34.1%) and failure (6.1%). A higher percentage of patients in the alert group received therapeutic intervention within 60 mins after the acute kidney injury alert (28.7% in alert group vs. 7.9% and 10.4% in the pre- and postalert control groups, respectively, p μ .001). In the alert group, more patients received fluid therapy (23.0% vs. 4.9% and 9.2%, p μ .01), diuretics (4.2% vs. 2.6% and 0.8%, p μ .001), or vasopressors (3.9% vs. 1.1% and 0.8%, p μ .001). Furthermore, these patients had a shorter time to intervention (p μ .001). A higher proportion of patients in the alert group showed return to a baseline kidney function within 8 hrs after an acute kidney injury alert "from normal to risk" compared with patients in the control group (p = .048). The real-time alerting of every worsening RIFLE class by the acute kidney injury sniffer increased the number and timeliness of early therapeutic interventions

Early mobilization of acute whiplash injuries.

PubMed Central

Mealy, K; Brennan, H; Fenelon, G C

1986-01-01

Acute whiplash injuries are a common cause of soft tissue trauma for which the standard treatment is rest and initial immobilisation with a soft cervical collar. Because the efficacy of this treatment is unknown a randomised study in 61 patients was carried out comparing the standard treatment with an alternative regimen of early active mobilisation. Results showed that eight weeks after the accident the degree of improvement seen in the actively treated group compared with the group given standard treatment was significantly greater for both cervical movement (p less than 0.05) and intensity of pain (p less than 0.0125). PMID:3081211

The Incidence of Acute Traumatic Tendon Injuries in the Hand and Wrist: A 10-Year Population-based Study

PubMed Central

de Jong, Johanna P.; Nguyen, Jesse T.; Sonnema, Anne J. M.; Nguyen, Emily C.; Amadio, Peter C.

2014-01-01

Background Acute traumatic tendon injuries of the hand and wrist are commonly encountered in the emergency department. Despite the frequency, few studies have examined the true incidence of acute traumatic tendon injuries in the hand and wrist or compared the incidences of both extensor and flexor tendon injuries. Methods We performed a retrospective population-based cohort study of all acute traumatic tendon injuries of the hand and wrist in a mixed urban and rural Midwest county in the United States between 2001-2010. A regional epidemiologic database and medical codes were used to identify index cases. Epidemiologic information including occupation, year of injury, mechanism of injury and the injured tendon and zone were recorded. Results During the 10-year study period there was an incidence rate of 33.2 injuries per 100,000 person-years. There was a decreasing rate of injury during the study period. Highest incidence of injury occurred at 20-29 years of age. There was significant association between injury rate and age, and males had a higher incidence than females. The majority of cases involved a single tendon, with extensor tendon injuries occurring more frequently than flexor tendons. Typically, extensor tendon injuries involved zone three of the index finger, while flexor tendons involved zone two of the index finger. Work-related injuries accounted for 24.9% of acute traumatic tendon injuries. The occupations of work-related injuries were assigned to major groups defined by the 2010 Standard Occupational Classification structure. After assigning these patients' occupations to respective major groups, the most common groups work-related injuries occurred in construction and extraction occupations (44.2%), food preparation and serving related occupations (14.4%), and transportation and material moving occupations (12.5%). Conclusions Epidemiology data enhances our knowledge of injury patterns and may play a role in the prevention and treatment of future

Impact of acute versus prolonged exercise and dehydration on kidney function and injury.

PubMed

Bongers, Coen C W G; Alsady, Mohammad; Nijenhuis, Tom; Tulp, Anouk D M; Eijsvogels, Thijs M H; Deen, Peter M T; Hopman, Maria T E

2018-06-01

Exercise and dehydration may be associated with a compromised kidney function and potential signs of kidney injury. However, the kidney responses to exercise of different durations and hypohydration levels are not yet known. Therefore, we aimed to compare the effects of acute versus prolonged exercise and dehydration on estimated glomerular filtration rate (eGFR) and kidney injury biomarkers in healthy male adults. A total of 35 subjects (23 ± 3 years) were included and invited for two study visits. Visit 1 consisted of a maximal cycling test. On Visit 2, subjects performed a submaximal exercise test at 80% of maximal heart rate until 3% hypohydration. Blood and urine samples were taken at baseline, after 30 min of exercise (acute effects; low level of hypohydration) and after 150 min of exercise or when 3% hypohydration was achieved (prolonged effects, high level of hypohydration). Urinary outcome parameters were corrected for urinary cystatin C, creatinine, and osmolality. Subjects dehydrated on average 0.6 ± 0.3% and 2.9 ± 0.7% after acute and prolonged exercise, respectively (P < 0.001). The eGFR cystatin C did not differ between baseline and acute exercise (118 ± 11 vs. 116 ± 12 mL/min/1.73 m 2 , P = 0.12), whereas eGFR cystatin C was significantly lower after prolonged exercise (103 ± 16 mL/min/1.73 m 2 , P < 0.001). We found no difference in osmolality corrected uKIM1 concentrations after acute and prolonged exercise (P > 0.05), and elevated osmolality corrected uNGAL concentrations after acute and prolonged exercise (all P-values < 0.05). In conclusion, acute exercise did barely impact on eGFR cystatin C and kidney injury biomarkers, whereas prolonged exercise is associated with a decline in eGFR cystatin C and increased biomarkers for kidney injury. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) protects against cisplatin-induced acute kidney injury.

PubMed

Yang, Yunwen; Yu, Xiaowen; Zhang, Yue; Ding, Guixia; Zhu, Chunhua; Huang, Songming; Jia, Zhanjun; Zhang, Aihua

2018-04-16

Renal hypoxia occurs in acute kidney injury (AKI) of various etiologies. Activation of hypoxia-inducible transcription factor (HIF) has been identified as an important mechanism of cellular adaptation to low oxygen. Preconditional HIF activation protects against AKI, suggesting a new approach in AKI treatment. HIF is degraded under normoxic conditions mediated by oxygen-dependent hydroxylation of specific prolyl residues of the regulative α-subunits by HIF prolyl hydroxylases (PHD). FG-4592 is a novel, orally active, small-molecule HIF PHD inhibitor for the treatment of anemia in patients with chronic kidney disease (CKD). The current study aimed to evaluate the effect of FG-4592 (Roxadustat) on cis -diamminedichloroplatinum (cisplatin)-induced kidney injury. In mice, pretreatment with FG-4592 markedly ameliorated cisplatin-induced kidney injury as shown by the improved renal function (blood urea nitrogen (BUN), serum creatinine (Scr), and cystatin C) and kidney morphology (periodic acid-Schiff (PAS) staining) in line with a robust blockade of renal tubular injury markers of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Meanwhile, the renal apoptosis and inflammation induced by cisplatin were also strikingly attenuated in FG-4592-treated mice. Along with the protective effects shown above, FG-4592 pretreatment strongly enhanced HIF-1α in tubular cells, as well as the expressions of HIF target genes. FG-4592 alone did not affect the renal function and morphology in mice. In vitro , FG-4592 treatment significantly up-regulated HIF-1α and protected the tubular cells against cisplatin-induced apoptosis. In summary, FG-4592 treatment remarkably ameliorated the cisplatin-induced kidney injury possibly through the stabilization of HIF. Thus, besides the role in treating CKD anemia, the clinical use of FG-4592 also could be extended to AKI. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical

Respiratory infections and acute lung injury in systemic illness.

PubMed

Skerrett, S J; Niederman, M S; Fein, A M

1989-12-01

syndrome and identified how it may lead to lung injury, usually by indirect means, through activation of inflammatory mediators that are carried to the lung via the vasculature. Although it is frequently impossible to predict which specific patient with systemic sepsis will develop acute lung injury, the current state of knowledge does permit us to identify high-risk individuals. Surprisingly, clinical assessment rather than biochemical testing is the best predictor of the development of acute lung injury. Patients with severe injury, profound shock and multiple systemic insults are most prone to acute lung injury in the presence of systemic sepsis.(ABSTRACT TRUNCATED AT 400 WORDS)

Thaliporphine Derivative Improves Acute Lung Injury after Traumatic Brain Injury

PubMed Central

Chen, Gunng-Shinng; Huang, Kuo-Feng; Huang, Chien-Chu; Wang, Jia-Yi

2015-01-01

Acute lung injury (ALI) occurs frequently in patients with severe traumatic brain injury (TBI) and is associated with a poor clinical outcome. Aquaporins (AQPs), particularly AQP1 and AQP4, maintain water balances between the epithelial and microvascular domains of the lung. Since pulmonary edema (PE) usually occurs in the TBI-induced ALI patients, we investigated the effects of a thaliporphine derivative, TM-1, on the expression of AQPs and histological outcomes in the lung following TBI in rats. TM-1 administered (10 mg/kg, intraperitoneal injection) at 3 or 4 h after TBI significantly reduced the elevated mRNA expression and protein levels of AQP1 and AQP4 and diminished the wet/dry weight ratio, which reflects PE, in the lung at 8 and 24 h after TBI. Postinjury TM-1 administration also improved histopathological changes at 8 and 24 h after TBI. PE was accompanied with tissue pathological changes because a positive correlation between the lung injury score and the wet/dry weight ratio in the same animal was observed. Postinjury administration of TM-1 improved ALI and reduced PE at 8 and 24 h following TBI. The pulmonary-protective effect of TM-1 may be attributed to, at least in part, downregulation of AQP1 and AQP4 expression after TBI. PMID:25705683

Levetiracetam as a possible contributor to acute kidney injury.

PubMed

Spengler, Danielle C; Montouris, Georgia D; Hohler, Anna D

2014-08-01

Levetiracetam is an antiepileptic medication that has been reported to be both well-tolerated and effective in treating generalized tonic-clonic, myoclonic, and partial-onset seizures. The adverse effects most commonly reported in tolerability trials include somnolence, fatigue/asthenia, headaches, dizziness, and nausea. However, there have been a few reports suggesting possible detrimental effects of levetiracetam on renal function. Here we describe the case of a previously healthy 23-year-old female patient who developed acute kidney injury 1 day after the initiation of levetiracetam therapy for new-onset seizures. Based on the time course of the patient's rise in serum creatinine and the exclusion of other causes, this case suggests that levetiracetam use contributed to the acute kidney injury. Levetiracetam is a widely used drug that has been reported to be generally tolerable and effective; however, it has the potential to negatively affect renal function. This potential consequence of therapy should be considered when deciding whether or not to prescribe this medication, and renal function should be monitored during treatment. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

Association of prehospitalization aspirin therapy and acute lung injury: results of a multicenter international observational study of at-risk patients.

PubMed

Kor, Daryl J; Erlich, Jason; Gong, Michelle N; Malinchoc, Michael; Carter, Rickey E; Gajic, Ognjen; Talmor, Daniel S

2011-11-01

To evaluate the association between prehospitalization aspirin therapy and incident acute lung injury in a heterogeneous cohort of at-risk medical patients. This is a secondary analysis of a prospective multicenter international cohort investigation. Multicenter observational study including 20 US hospitals and two hospitals in Turkey. Consecutive, adult, nonsurgical patients admitted to the hospital with at least one major risk factor for acute lung injury. None. Baseline characteristics and acute lung injury risk factors/modifiers were identified. The presence of aspirin therapy and the propensity to receive this therapy were determined. The primary outcome was acute lung injury during hospitalization. Secondary outcomes included intensive care unit and hospital mortality and intensive care unit and hospital length of stay. Twenty-two hospitals enrolled 3855 at-risk patients over a 6-month period. Nine hundred seventy-six (25.3%) were receiving aspirin at the time of hospitalization. Two hundred forty (6.2%) patients developed acute lung injury. Univariate analysis noted a reduced incidence of acute lung injury in those receiving aspirin therapy (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.46-0.90; p = .010). This association was attenuated in a stratified analysis based on deciles of aspirin propensity scores (Cochran-Mantel-Haenszel pooled OR, 0.70; 95% CI, 0.48-1.03; p = .072). After adjusting for the propensity to receive aspirin therapy, no statistically significant associations between prehospitalization aspirin therapy and acute lung injury were identified; however, a prospective clinical trial to further evaluate this association appears warranted.

Serum neutrophil gelatinase-associated lipocalin (NGAL) as a marker of acute kidney injury in critically ill children with septic shock.

PubMed

Wheeler, Derek S; Devarajan, Prasad; Ma, Qing; Harmon, Kelli; Monaco, Marie; Cvijanovich, Natalie; Wong, Hector R

2008-04-01

To validate serum neutrophil gelatinase-associated lipocalin (NGAL) as an early biomarker for acute kidney injury in critically ill children with septic shock. Observational cohort study. Fifteen North American pediatric intensive care units (PICUs). A total of 143 critically ill children with systemic inflammatory response syndrome (SIRS) or septic shock and 25 healthy controls. None. Serum NGAL was measured during the first 24 hrs of admission to the PICU. Acute kidney injury was defined as a blood urea nitrogen concentration >100 mg/dL, serum creatinine >2 mg/dL in the absence of preexisting renal disease, or the need for dialysis. There was a significant difference in serum NGAL between healthy children (median 80 ng/mL, interquartile ratio [IQR] 55.5-85.5 ng/mL), critically ill children with SIRS (median 107.5 ng/mL, IQR 89-178.5 ng/mL), and critically ill children with septic shock (median 302 ng/mL, IQR 151-570 ng/mL; p < .001). Acute kidney injury developed in 22 of 143 (15.4%) critically ill children. Serum NGAL was significantly increased in critically ill children with acute kidney injury (median 355 ng/mL, IQR 166-1322 ng/mL) compared with those without acute kidney injury (median 186 ng/mL, IQR 98-365 ng/mL; p = .009). Serum NGAL is a highly sensitive but nonspecific predictor of acute kidney injury in critically ill children with septic shock. Further validation of serum NGAL as a biomarker of acute kidney injury in this population is warranted.

Anterolateral ligament abnormalities in patients with acute anterior cruciate ligament rupture are associated with lateral meniscal and osseous injuries.

PubMed

Van Dyck, Pieter; Clockaerts, Stefan; Vanhoenacker, Filip M; Lambrecht, Valérie; Wouters, Kristien; De Smet, Eline; Gielen, Jan L; Parizel, Paul M

2016-10-01

To determine the frequency of anterolateral ligament (ALL) injury in patients with acute anterior cruciate ligament (ACL) rupture and to analyse its associated injury patterns. Ninety patients with acute ACL rupture for which MRI was obtained within 8 weeks after the initial trauma were retrospectively identified. Two radiologists assessed the status of the ALL on MRI by consensus. The presence or absence of an ALL abnormality was compared with the existence of medial and lateral meniscal tears diagnosed during arthroscopy. Associated collateral ligament and osseous injuries were documented with MRI. Forty-one of 90 knees (46 %) demonstrated ALL abnormalities on MRI. Of 49 knees with intact ALL, 15 (31 %) had a torn lateral meniscus as compared to 25 torn lateral menisci in 41 knees (61 %) with abnormal ALL (p = 0.008). Collateral ligament (p ≤ 0.05) and osseous injuries (p = 0.0037) were more frequent and severe in ALL-injured as compared with ALL-intact knees. ALL injuries are fairly common in patients with acute ACL rupture and are statistically significantly associated with lateral meniscal, collateral ligament and osseous injuries. • ALL injuries are fairly common in patients with acute ACL rupture. • ALL injuries are highly associated with lateral meniscal and osseous injuries. • MRI assessment of ACL-injured knees should include evaluation of the ALL.

Bromelain in the early phase of healing in acute crush Achilles tendon injury.

PubMed

Aiyegbusi, A I; Duru, F I O; Anunobi, C C; Noronha, C C; Okanlawon, A O

2011-01-01

Bromelain, an enzyme extracted from the stem of the pineapple plant has been proposed as a treatment for reducing pain and swelling following acute muscle injuries but studies are yet to be done on its effect on tendon healing. This study therefore investigated the effects of bromelain on tenocyte proliferation and the tendon malondialdehyde (MDA) level in the early stage of healing in a crush injury to the Achilles tendon of Sprague-Dawley rats. Twenty four male rats were divided randomly into three groups; groups 2 and 3 had induced crush injury to the left Achilles tendon. Group 1; nil injury and nil treatment, Group 2; nil treatment, Group 3; oral bromelain treatment. Bromelain was given at a dosage of 7 mg/kg body weight daily over the first 14 days post-injury. On day 15 post injury, the animals were killed and the tendons excised and processed for histological study and MDA assay. The results showed a significant increase in the tenocyte population in the bromelain group; p < 0.05. There was, however, no significant difference in the MDA level. Based on this study, 600 GDU bromelain given once daily in acute tendon injury at a dosage of 7 mg/kg promoted healing by stimulating tenocyte proliferation. Copyright © 2010 John Wiley & Sons, Ltd.

Development of a Lubricant Therapy to Prevent Development of Osteoarthritis after Acute Injury of Synovial Joints

DTIC Science & Technology

2015-10-01

AD______________ AWARD NUMBER: W81XWH-14-1-0562 TITLE: Development of a Lubricant Therapy to Prevent Development of Osteoarthritis after Acute...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Development of a Lubricant Therapy to Prevent Development of Osteoarthritis after Acute Injury of Synovial...early-onset osteoarthritis after traumatic joint injury remains a clinical challenge and may be associated with the poor lubricant quality of the

Factors secreted from dental pulp stem cells show multifaceted benefits for treating acute lung injury in mice.

PubMed

Wakayama, Hirotaka; Hashimoto, Naozumi; Matsushita, Yoshihiro; Matsubara, Kohki; Yamamoto, Noriyuki; Hasegawa, Yoshinori; Ueda, Minoru; Yamamoto, Akihito

2015-08-01

Acute respiratory distress syndrome (ARDS) is a severe inflammatory disorder characterized by acute respiratory failure, resulting from severe, destructive lung inflammation and irreversible lung fibrosis. We evaluated the use of stem cells derived from human exfoliated deciduous teeth (SHEDs) or SHED-derived serum-free conditioned medium (SHED-CM) as treatments for bleomycin (BLM)-induced mice acute lung injury (ALI), exhibiting several pathogenic features associated with the human disease ARDS. Mice with BLM-induced ALI with or without SHED or SHED-CM treatment were examined for weight loss and survival. The lung tissue was characterized by histological and real-time quantitative polymerase chain reaction analysis. The effects of SHED-CM on macrophage differentiation in vitro were also assessed. A single intravenous administration of either SHEDs or SHED-CM attenuated the lung injury and weight loss in BLM-treated mice and improved their survival rate. Similar recovery levels were seen in the SHEDs and SHED-CM treatment groups, suggesting that SHED improves ALI by paracrine mechanisms. SHED-CM contained multiple therapeutic factors involved in lung-regenerative mechanisms. Importantly, SHED-CM attenuated the BLM-induced pro-inflammatory response and generated an anti-inflammatory/tissue-regenerating environment, accompanied by the induction of anti-inflammatory M2-like lung macrophages. Furthermore, SHED-CM promoted the in vitro differentiation of bone marrow-derived macrophages into M2-like cells, which expressed high levels of Arginase1, CD206 and Ym-1. Our results suggest that SHED-secreted factors provide multifaceted therapeutic effects, including a strong M2-inducing activity, for treating BLM-induced ALI. This work may open new avenues for research on stem cell-based ARDS therapies. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Autophagy inhibitor 3-methyladenine protects against endothelial cell barrier dysfunction in acute lung injury.

PubMed

Slavin, Spencer A; Leonard, Antony; Grose, Valerie; Fazal, Fabeha; Rahman, Arshad

2018-03-01

Autophagy is an evolutionarily conserved cellular process that facilitates the continuous recycling of intracellular components (organelles and proteins) and provides an alternative source of energy when nutrients are scarce. Recent studies have implicated autophagy in many disorders, including pulmonary diseases. However, the role of autophagy in endothelial cell (EC) barrier dysfunction and its relevance in the context of acute lung injury (ALI) remain uncertain. Here, we provide evidence that autophagy is a critical component of EC barrier disruption in ALI. Using an aerosolized bacterial lipopolysaccharide (LPS) inhalation mouse model of ALI, we found that administration of the autophagy inhibitor 3-methyladenine (3-MA), either prophylactically or therapeutically, markedly reduced lung vascular leakage and tissue edema. 3-MA was also effective in reducing the levels of proinflammatory mediators and lung neutrophil sequestration induced by LPS. To test the possibility that autophagy in EC could contribute to lung vascular injury, we addressed its role in the mechanism of EC barrier disruption. Knockdown of ATG5, an essential regulator of autophagy, attenuated thrombin-induced EC barrier disruption, confirming the involvement of autophagy in the response. Similarly, exposure of cells to 3-MA, either before or after thrombin, protected against EC barrier dysfunction by inhibiting the cleavage and loss of vascular endothelial cadherin at adherens junctions, as well as formation of actin stress fibers. 3-MA also reversed LPS-induced EC barrier disruption. Together, these data imply a role of autophagy in lung vascular injury and reveal the protective and therapeutic utility of 3-MA against ALI.

Sports‐related acute and chronic avulsion injuries in children and adolescents with special emphasis on tennis

PubMed Central

Vandervliet, Everhard J M; Vanhoenacker, Filip M; Snoeckx, Annemie; Gielen, Jan L; Van Dyck, Pieter; Parizel, Paul M

2007-01-01

Acute and chronic sports‐related muscle and tendon injuries are not infrequent in youngsters. In particular, the physis is prone to trauma as it constitutes the weakest part of the immature skeleton. The type of sports activity determines the location of the lesion. Most commonly, apophyses of the hip and pelvis are subject to avulsion. The purpose of this paper is to give a short overview of the pathogenesis, location, prevalence and imaging characteristics of acute and chronic avulsion injuries in the immature skeleton, with special emphasis on tennis‐related injuries. Tennis‐related injuries particularly involve apophyses of the ischial tuberosity, the anterior inferior or superior iliac spine and the iliac crest. PMID:17586583

Peritoneal dialysis vs. haemodialysis in the management of paediatric acute kidney injury in Kano, Nigeria: a cost analysis.

PubMed

Obiagwu, Patience N; Abdu, Aliyu

2015-01-01

To determine the cost of the dialytic management of paediatric acute kidney injury in a low-income country. All children under the age of 15 years, who had either peritoneal dialysis or haemodialysis for acute kidney injury in Aminu Kano Teaching Hospital over a 1-year period, were studied. The average cost of each dialysis modality was estimated. Of 20 children, who had dialysis for acute kidney injury, 12 (60%) had haemodialysis and 8 (40%) had peritoneal dialysis. The mean cost for haemodialysis exceeded that of peritoneal dialysis ($363.33 vs. $311.66, t = 1.04, P = 0.313) with the mean cost of consumables significantly accounting for most of the cost variation ($248.49 vs. $164.73, t = 2.91, P = 0.009). Mean costs of nephrologist visit and nursing were not found to be significant. Peritoneal dialysis is the less costly alternative for managing acute kidney injury in children in our environment. © 2014 John Wiley & Sons Ltd.

Suramin protects from cisplatin-induced acute kidney injury

PubMed Central

Dupre, Tess V.; Doll, Mark A.; Shah, Parag P.; Sharp, Cierra N.; Kiefer, Alex; Scherzer, Michael T.; Saurabh, Kumar; Saforo, Doug; Siow, Deanna; Casson, Lavona; Arteel, Gavin E.; Jenson, Alfred Bennett; Megyesi, Judit; Schnellmann, Rick G.; Beverly, Levi J.

2015-01-01

Cisplatin, a commonly used cancer chemotherapeutic, has a dose-limiting side effect of nephrotoxicity. Approximately 30% of patients administered cisplatin suffer from kidney injury, and there are limited treatment options for the treatment of cisplatin-induced kidney injury. Suramin, which is Federal Drug Administration-approved for the treatment of trypanosomiasis, improves kidney function after various forms of kidney injury in rodent models. We hypothesized that suramin would attenuate cisplatin-induced kidney injury. Suramin treatment before cisplatin administration reduced cisplatin-induced decreases in kidney function and injury. Furthermore, suramin attenuated cisplatin-induced expression of inflammatory cytokines and chemokines, endoplasmic reticulum stress, and apoptosis in the kidney cortex. Treatment of mice with suramin 24 h after cisplatin also improved kidney function, suggesting that the mechanism of protection is not by inhibition of tubular cisplatin uptake or its metabolism to nephrotoxic species. If suramin is to be used in the context of cancer, then it cannot prevent cisplatin-induced cytotoxicity of cancer cells. Suramin did not alter the dose-response curve of cisplatin in lung adenocarcinoma cells in vitro. In addition, suramin pretreatment of mice harboring lung adenocarcinomas did not alter the initial cytotoxic effects of cisplatin (DNA damage and apoptosis) on tumor cells. These results provide evidence that suramin has potential as a renoprotective agent for the treatment/prevention of cisplatin-induced acute kidney injury and justify future long-term preclinical studies using cotreatment of suramin and cisplatin in mouse models of cancer. PMID:26661653

Ataxia Telangiectasia–Mutated Gene Polymorphisms and Acute Normal Tissue Injuries in Cancer Patients After Radiation Therapy: A Systematic Review and Meta-analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong, Lihua; Cui, Jingkun; Tang, Fengjiao

Purpose: Studies of the association between ataxia telangiectasia–mutated (ATM) gene polymorphisms and acute radiation injuries are often small in sample size, and the results are inconsistent. We conducted the first meta-analysis to provide a systematic review of published findings. Methods and Materials: Publications were identified by searching PubMed up to April 25, 2014. Primary meta-analysis was performed for all acute radiation injuries, and subgroup meta-analyses were based on clinical endpoint. The influence of sample size and radiation injury incidence on genetic effects was estimated in sensitivity analyses. Power calculations were also conducted. Results: The meta-analysis was conducted on the ATMmore » polymorphism rs1801516, including 5 studies with 1588 participants. For all studies, the cut-off for differentiating cases from controls was grade 2 acute radiation injuries. The primary meta-analysis showed a significant association with overall acute radiation injuries (allelic model: odds ratio = 1.33, 95% confidence interval: 1.04-1.71). Subgroup analyses detected an association between the rs1801516 polymorphism and a significant increase in urinary and lower gastrointestinal injuries and an increase in skin injury that was not statistically significant. There was no between-study heterogeneity in any meta-analyses. In the sensitivity analyses, small studies did not show larger effects than large studies. In addition, studies with high incidence of acute radiation injuries showed larger effects than studies with low incidence. Power calculations revealed that the statistical power of the primary meta-analysis was borderline, whereas there was adequate power for the subgroup analysis of studies with high incidence of acute radiation injuries. Conclusions: Our meta-analysis showed a consistency of the results from the overall and subgroup analyses. We also showed that the genetic effect of the rs1801516 polymorphism on acute radiation injuries

Noninvasive ventilation for patients with acute lung injury or acute respiratory distress syndrome.

PubMed

Nava, Stefano; Schreiber, Ania; Domenighetti, Guido

2011-10-01

Few studies have been performed on noninvasive ventilation (NIV) to treat hypoxic acute respiratory failure in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). The outcomes of these patients, for whom endotracheal intubation is not mandatory, depend on the degree of hypoxia, the presence of comorbidities and complications, and their illness severity. The use of NIV as an alternative to invasive ventilation in severely hypoxemic patients with ARDS (ie, P(aO(2))/F(IO(2)) < 200) is not generally advisable and should be limited to hemodynamically stable patients who can be closely monitored in an intensive care unit by highly skilled staff. Early NIV application may be extremely helpful in immunocompromised patients with pulmonary infiltrates, in whom intubation dramatically increases the risk of infection, pneumonia, and death. The use of NIV in patients with severe acute respiratory syndrome and other airborne diseases has generated debate, despite encouraging clinical results, mainly because of safety issues. Overall, the high rate of NIV failure suggests a cautious approach to NIV use in patients with ALI/ARDS, including early initiation, intensive monitoring, and prompt intubation if signs of NIV failure emerge.

Acute kidney injury by radiographic contrast media: pathogenesis and prevention.

PubMed

Andreucci, Michele; Faga, Teresa; Pisani, Antonio; Sabbatini, Massimo; Michael, Ashour

2014-01-01

It is well known that iodinated radiographic contrast media may cause kidney dysfunction, particularly in patients with preexisting renal impairment associated with diabetes. This dysfunction, when severe, will cause acute renal failure (ARF). We may define contrast-induced Acute Kidney Injury (AKI) as ARF occurring within 24-72 hrs after the intravascular injection of iodinated radiographic contrast media that cannot be attributed to other causes. The mechanisms underlying contrast media nephrotoxicity have not been fully elucidated and may be due to several factors, including renal ischaemia, particularly in the renal medulla, the formation of reactive oxygen species (ROS), reduction of nitric oxide (NO) production, and tubular epithelial and vascular endothelial injury. However, contrast-induced AKI can be prevented, but in order to do so, we need to know the risk factors. We have reviewed the risk factors for contrast-induced AKI and measures for its prevention, providing a long list of references enabling readers to deeply evaluate them both.

Acute Kidney Injury by Radiographic Contrast Media: Pathogenesis and Prevention

PubMed Central

Faga, Teresa; Pisani, Antonio; Michael, Ashour

2014-01-01

It is well known that iodinated radiographic contrast media may cause kidney dysfunction, particularly in patients with preexisting renal impairment associated with diabetes. This dysfunction, when severe, will cause acute renal failure (ARF). We may define contrast-induced Acute Kidney Injury (AKI) as ARF occurring within 24–72 hrs after the intravascular injection of iodinated radiographic contrast media that cannot be attributed to other causes. The mechanisms underlying contrast media nephrotoxicity have not been fully elucidated and may be due to several factors, including renal ischaemia, particularly in the renal medulla, the formation of reactive oxygen species (ROS), reduction of nitric oxide (NO) production, and tubular epithelial and vascular endothelial injury. However, contrast-induced AKI can be prevented, but in order to do so, we need to know the risk factors. We have reviewed the risk factors for contrast-induced AKI and measures for its prevention, providing a long list of references enabling readers to deeply evaluate them both. PMID:25197639

Cognitive appraisals and emotional status following a spinal cord injury in post-acute rehabilitation.

PubMed

Eaton, Rebecca; Jones, Kevin; Duff, Jane

2018-06-12

Retrospective, cross-sectional study. To investigate the factor structure of the ADAPSS-short form (ADAPSS-SF) in an acutely injured SCI population and to assess the relationship between cognitive appraisals made in the initial phase of rehabilitation and the experience of anxiety and depression. National Spinal Injuries Centre, UK. Participants were acutely injured patients admitted to the NSIC over 35 months. Cognitive appraisals were measured using the ADAPSS-SF; psychological distress was measured using the HADS. Individual profiles, including demographics and injury characteristics, were collected. Principle Component Analysis with oblique rotation demonstrated a coherent two-factor structure of the ADAPSS-SF: resilience and loss. Correlational analysis found that individuals who negatively appraised their injury were more likely to report lower mood. Findings identified four vulnerable subgroups that were more likely to negatively appraise their injury: females, individuals older at the time of SCI, individuals with AIS-A injuries and individuals whose SCI was acquired through assault. Hierarchical regression analysis reported that resilience and loss factors were significant predictors of depression. Gender, resilience and loss factors were significant predictors of anxiety. Cognitive appraisals accounted for more variance in mood above biological markers. Findings support a two-factor structure and validity of ADAPSS-SF in acute SCI rehabilitation. The study provides support for the role of cognitive appraisals in psychological adjustment in the early phases of rehabilitation, above injury characteristics. Findings highlighted the vulnerable subgroups that are more likely to initially endorse negative appraisals, which may influence clinical practice and provides an avenue for further research.

Cystatin C as an early marker of acute kidney injury in septic shock.

PubMed

Ortuño-Andériz, F; Cabello-Clotet, N; Vidart-Simón, N; Postigo-Hernández, C; Domingo-Marín, S; Sánchez-García, M

2015-03-01

To describe the utility of determining plasma cystatinC concentrations in the diagnosis of acute incident kidney injury in septic shock. Prospective series of 50 patients with septic shock and plasma creatinine levels <2mg/dL hospitalized in an intensive care unit. Clinical and laboratory follow-ups were conducted, with measurements of cystatinC, urea and plasma creatinine levels from the diagnosis of septic shock to 5days later. The severity of the septic shock was assessed with the RIFLE scale. Twenty patients (40%) developed acute kidney injury: 8 (16%) were categorized as RIFLE-R, 5 (10%) as RIFLE-I and 7 (14%) as RIFLE-F. All patients categorized as RIFLE-F required extracorporeal renal clearance. Eighteen (36%) patients died, 8 (20%) of whom had developed acute kidney injury in their evolution. There was poor correlation between plasma creatinine and cystatin C levels (r=.501; P=.001), which disappeared upon reaching any degree of renal impairment on the RIFLE scale. CystatinC levels increased earlier and were better able to identify patients who would develop serious renal function impairment (RIFLE-F) than creatinine and urea levels. The initial cystatinC levels were related to mortality at 30days (OR=1.16; 95%CI: 03-.85). For patients who developed acute septic kidney injury, the plasma cystatinC levels increased before the classical markers of renal function. CystatinC also constitutes a severity biomarker that correlates with progression to RIFLE-F, the need for extrarenal clearance and, ultimately, mortality. This precocity could be useful for starting measures that prevent the progression of renal dysfunction. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Acute injuries in soccer, ice hockey, volleyball, basketball, judo, and karate: analysis of national registry data.

PubMed

Kujala, U M; Taimela, S; Antti-Poika, I; Orava, S; Tuominen, R; Myllynen, P

1995-12-02

To determine the acute injury profile in each of six sports and compare the injury rates between the sports. Analysis of national sports injury insurance registry data. Finland during 1987-91. 621,691 person years of exposure among participants in soccer, ice hockey, volleyball, basketball, judo, or karate. Acute sports injuries requiring medical treatment and reported to the insurance company on structured forms by the patients and their doctors. 54,186 sports injuries were recorded. Injury rates were low in athletes aged under 15, while 20-24 year olds had the highest rates. Differences in injury rates between the sports were minor in this adult age group. Overall injury rates were higher in sports entailing more frequent and powerful body contact. Each sport had a specific injury profile. Fractures and dental injuries were most common in ice hockey and karate and least frequent in volleyball. Knee injuries were the most common cause of permanent disability. Based on the defined injury profiles in the different sports it is recommended that sports specific preventive measures should be employed to decrease the number of violent contacts between athletes, including improved game rules supported by careful refereeing. To prevent dental injuries the wearing of mouth guards should be encouraged, especially in ice hockey, karate, and basketball.

Clinical assessment of acute lateral ankle sprain injuries (ROAST): 2019 consensus statement and recommendations of the International Ankle Consortium.

PubMed

Delahunt, Eamonn; Bleakley, Chris M; Bossard, Daniela S; Caulfield, Brian M; Docherty, Carrie L; Doherty, Cailbhe; Fourchet, François; Fong, Daniel T; Hertel, Jay; Hiller, Claire E; Kaminski, Thomas W; McKeon, Patrick O; Refshauge, Kathryn M; Remus, Alexandria; Verhagen, Evert; Vicenzino, Bill T; Wikstrom, Erik A; Gribble, Phillip A

2018-06-09

Lateral ankle sprain injury is the most common musculoskeletal injury incurred by individuals who participate in sports and recreational physical activities. Following initial injury, a high proportion of individuals develop long-term injury-associated symptoms and chronic ankle instability. The development of chronic ankle instability is consequent on the interaction of mechanical and sensorimotor insufficiencies/impairments that manifest following acute lateral ankle sprain injury. To reduce the propensity for developing chronic ankle instability, clinical assessments should evaluate whether patients in the acute phase following lateral ankle sprain injury exhibit any mechanical and/or sensorimotor impairments. This modified Delphi study was undertaken under the auspices of the executive committee of the International Ankle Consortium. The primary aim was to develop recommendations, based on expert (n=14) consensus, for structured clinical assessment of acute lateral ankle sprain injuries. After two modified Delphi rounds, consensus was achieved on the clinical assessment of acute lateral ankle sprain injuries. Consensus was reached on a minimum standard clinical diagnostic assessment. Key components of this clinical diagnostic assessment include: establishing the mechanism of injury, as well as the assessment of ankle joint bones and ligaments. Through consensus, the expert panel also developed the International Ankle Consortium Rehabilitation-Oriented ASsessmenT (ROAST). The International Ankle Consortium ROAST will help clinicians identify mechanical and/or sensorimotor impairments that are associated with chronic ankle instability. This consensus statement from the International Ankle Consortium aims to be a key resource for clinicians who regularly assess individuals with acute lateral ankle sprain injuries. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted

Prone positioning ventilation for treatment of acute lung injury and acute respiratory distress syndrome.

PubMed

Lan, Mei-juan; He, Xiao-di

2009-08-01

Patients who are diagnosed with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) usually have ventilation-perfusion mismatch, severe decrease in lung capacity, and gas exchange abnormalities. Health care workers have implemented various strategies in an attempt to compensate for these pathological alterations. By rotating patients with ALI/ARDS between the supine and prone position, it is possible to achieve a significant improvement in PaO2/FiO2, decrease shunting and therefore improve oxygenation without use of expensive, invasive and experimental procedures. Prone positioning is a safe and effective way to improve ventilation when conventional strategies fail to initiate a patient response. Because a specific cure for ARDS is not available, the goal is to support the patients with therapies that cause the least amount of injury while the lungs have an opportunity to heal. Based on current data, a trial of prone positioning ventilation should be offered to the patients who have ALI/ARDS in the early course of the disease. Published studies exhibit substantial heterogeneity in clinical results, suggesting that an adequately sized study optimizing the duration of proning ventilation strategy is warranted to enable definitive conclusions to be drawn.

Lung protective mechanical ventilation and two year survival in patients with acute lung injury: prospective cohort study.

PubMed

Needham, Dale M; Colantuoni, Elizabeth; Mendez-Tellez, Pedro A; Dinglas, Victor D; Sevransky, Jonathan E; Dennison Himmelfarb, Cheryl R; Desai, Sanjay V; Shanholtz, Carl; Brower, Roy G; Pronovost, Peter J

2012-04-05

To evaluate the association of volume limited and pressure limited (lung protective) mechanical ventilation with two year survival in patients with acute lung injury. Prospective cohort study. 13 intensive care units at four hospitals in Baltimore, Maryland, USA. 485 consecutive mechanically ventilated patients with acute lung injury. Two year survival after onset of acute lung injury. 485 patients contributed data for 6240 eligible ventilator settings, as measured twice daily (median of eight eligible ventilator settings per patient; 41% of which adhered to lung protective ventilation). Of these patients, 311 (64%) died within two years. After adjusting for the total duration of ventilation and other relevant covariates, each additional ventilator setting adherent to lung protective ventilation was associated with a 3% decrease in the risk of mortality over two years (hazard ratio 0.97, 95% confidence interval 0.95 to 0.99, P=0.002). Compared with no adherence, the estimated absolute risk reduction in two year mortality for a prototypical patient with 50% adherence to lung protective ventilation was 4.0% (0.8% to 7.2%, P=0.012) and with 100% adherence was 7.8% (1.6% to 14.0%, P=0.011). Lung protective mechanical ventilation was associated with a substantial long term survival benefit for patients with acute lung injury. Greater use of lung protective ventilation in routine clinical practice could reduce long term mortality in patients with acute lung injury. Clinicaltrials.gov NCT00300248.

Prophylactic Administration of CN-105 Confers Neuroprotection Against Acute Brain Injury

DTIC Science & Technology

2017-10-01

105 was designed from the receptor binding face of apolipoprotein E, which is an endogenous protein that has been demonstrated to modify injury...apolipoprotein E (APOE - gene; apoE - protein ) polymorphism. There are three distinct apoE protein isoforms, designated apoE2, apoE3, and apoE4. Although there...data underscore the importance that apoE plays in mediating CNS responses to acute injury and neurodegeneration. The apoE protein was initially found

Acute hamstring injury in football players: Association between anatomical location and extent of injury-A large single-center MRI report.

PubMed

Crema, Michel D; Guermazi, Ali; Tol, Johannes L; Niu, Jingbo; Hamilton, Bruce; Roemer, Frank W

2016-04-01

To describe in detail the anatomic distribution of acute hamstring injuries in football players, and to assess the relationship between location and extent of edema and tears, all based on findings from MRI. Retrospective observational study. We included 275 consecutive male football players who had sustained acute hamstring injuries and had positive findings on MRI. For each subject, lesions were recorded at specific locations of the hamstring muscles, which were divided into proximal or distal: free tendon, myotendinous junction, muscle belly, and myofascial junction locations. For each lesion, we assessed the largest cross-sectional area of edema and/or tears. We calculated the prevalence of injuries by location. The relationships between locations and extent of edema and tears were assessed using a one-sample t-test, with significance set at p<0.05. The long head of biceps femoris (LHBF) was most commonly affected (56.5%). Overall, injuries were most common in the myotendinous junction and in proximal locations. The proximal myotendinous junction was associated with a greater extent of edema in the LHBF and semitendinosus (ST) muscles (p<0.05). Proximal locations in the LHBF had larger edema than distal locations (p<0.05). Distal locations in the ST muscle had larger tears than proximal locations (p<0.05). The proximal myotendinous junction (LHBF and ST muscles) and proximal locations (LHBF muscle) are more commonly affected and are associated with a greater extent of edema in acute hamstring muscle injury. Distal locations (ST muscle), however, seem to be more commonly associated with larger tears. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Effect of Ergothioneine on Acute Lung Injury and Inflammation in Cytokine Insufflated Rats

PubMed Central

Repine, John E.; Elkins, Nancy D.

2012-01-01

Objective The Acute Respiratory Distress Syndrome (ARDS), the most severe form of Acute Lung Injury (ALI), is a highly-fatal, diffuse non-cardiogenic edematous lung disorder. The pathogenesis of ARDS is unknown but lung inflammation and lung oxidative stress are likely contributing factors. Since no specific pharmacologic intervention exists for ARDS, our objective was to determine the effect of treatment with ergothioneine---a safe agent with multiple anti-inflammatory and antioxidant properties on the development of lung injury and inflammation in rats insufflated with cytokines found in lung lavages of ARDS patients. Method Sprague-Dawley rats (3-10/group) were given 15 mg/kg or 150 mg/kg L-ergothioneine intravenously 1 hour before or 18 hours after cytokine (IL-1 and IFNγ) insufflation. Lung injury (lavage LDH levels) and lung inflammation (lavage neutrophil numbers) were measured 24 hours after cytokine insufflation. Results Ergothioneine pre- and post- treatment generally decreased lung injury and lung inflammation in cytokine insufflated rats. Conclusion Ergothioneine should be considered for additional testing as a potential therapy for treating and preventing ARDS. PMID:22197759

Dual-phase CT for the assessment of acute vascular injuries in high-energy blunt trauma: the imaging findings and management implications.

PubMed

Iacobellis, Francesca; Ierardi, Anna M; Mazzei, Maria A; Magenta Biasina, Alberto; Carrafiello, Gianpaolo; Nicola, Refky; Scaglione, Mariano

2016-01-01

Acute vascular injuries are the second most common cause of fatalities in patients with multiple traumatic injuries; thus, prompt identification and management is essential for patient survival. Over the past few years, multidetector CT (MDCT) using dual-phase scanning protocol has become the imaging modality of choice in high-energy deceleration traumas. The objective of this article was to review the role of dual-phase MDCT in the identification and management of acute vascular injuries, particularly in the chest and abdomen following multiple traumatic injuries. In addition, this article will provide examples of MDCT features of acute vascular injuries with correlative surgical and interventional findings.

Dimethylthiourea ameliorates carbon tetrachloride-induced acute liver injury in ovariectomized mice.

PubMed

Mitazaki, Satoru; Kotajima, Natsumi; Matsuda, Sakiko; Ida, Naruki; Iide, Mina; Honma, Shigeyoshi; Suto, Miwako; Kato, Naho; Kuroda, Naohito; Hiraiwa, Kouichi; Yoshida, Makoto; Abe, Sumiko

2018-08-01

In order to clarify hepato-protective actions of estrogen, we examined the progress of carbon tetrachloride (CCl 4 )-induced acute liver injury (ALI) in sham and ovariectomized (ovx) mice and the effects of dimethylthiourea (DMTU), a hydroxyl radical scavenger, and meloxicam (Melo), a selective cox-2 inhibitor, on the development of CCl 4 -induced ALI. Female C57BL/6 J mice weighing 15-20 g were performed sham or ovx operation at 8 weeks of age. Blood and liver samples were collected 15 and 24 h after CCl 4 administration. Sham and ovx mice were given DMTU, Melo or saline intraperitoneally 30 min before CCl 4 or corn oil administration. ALT levels in ovx mice were significantly increased compared to those in sham mice. DMTU reduced ALT levels in ovx mice to the same levels as those in sham mice after CCl 4 injection. CCl 4 upregulated TNF-α, IL-6, cox-2 and iNOS expression in ovx mice compared to the levels in sham mice. DMTU significantly reduced cox-2 and iNOS expression levels upregulated by CCl 4 in ovx mice. However, pretreatment with Melo had no effects on ALT levels and the gene expression levels of TNF-α, IL-6 and HO-1 in either sham or ovx mice, indicating that cox-2 may not participate in increase of CCl 4 -induced ALI caused by estrogen deficiency. Ovariectomy accelerated the development of CCl 4 -induced acute liver injury, and DMTU reduced liver injury. These results suggest that estrogen may act as an antioxidant in the development CCl 4 -induced acute liver injury. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Measurement of renal blood flow by phase-contrast magnetic resonance imaging during septic acute kidney injury: a pilot investigation.

PubMed

Prowle, John R; Molan, Maurice P; Hornsey, Emma; Bellomo, Rinaldo

2012-06-01

In septic patients, decreased renal perfusion is considered to play a major role in the pathogenesis of acute kidney injury. However, the accurate measurement of renal blood flow in such patients is problematic and invasive. We sought to overcome such obstacles by measuring renal blood flow in septic patients with acute kidney injury using cine phase-contrast magnetic resonance imaging. Pilot observational study. University-affiliated general adult intensive care unit. Ten adult patients with established septic acute kidney injury and 11 normal volunteers. Cine phase-contrast magnetic resonance imaging measurement of renal blood flow and cardiac output. The median age of the study patients was 62.5 yrs and eight were male. At the time of magnetic resonance imaging, eight patients were mechanically ventilated, nine were on continuous hemofiltration, and five required vasopressors. Cine phase-contrast magnetic resonance imaging examinations were carried out without complication. Median renal blood flow was 482 mL/min (range 335-1137) in septic acute kidney injury and 1260 mL/min (range 791-1750) in healthy controls (p = .003). Renal blood flow indexed to body surface area was 244 mL/min/m2 (range 165-662) in septic acute kidney injury and 525 mL/min/m2 (range 438-869) in controls (p = .004). In patients with septic acute kidney injury, median cardiac index was 3.5 L/min/m2 (range 1.6-8.7), and median renal fraction of cardiac output was only 7.1% (range 4.4-10.8). There was no rank correlation between renal blood flow index and creatinine clearance in patients with septic acute kidney injury (r = .26, p = .45). Cine phase-contrast magnetic resonance imaging can be used to noninvasively and safely assess renal perfusion during critical illness in man. Near-simultaneous accurate measurement of cardiac output enables organ blood flow to be assessed in the context of the global circulation. Renal blood flow seems consistently reduced as a fraction of cardiac output in

MANAGEMENT OF ACUTE SPORTS INJURIES AND MEDICAL CONDITIONS BY PHYSICAL THERAPISTS: ASSESSMENT VIA CASE SCENARIOS

PubMed Central

Karges, Joy Renae; Salsbery, Mitchell A.; Smith, Danna; Stanley, Erica J.

2011-01-01

Purpose/Background: Some physical therapists (PTs) provide services at sporting events, but there are limited studies investigating whether PTs are properly prepared to provide such services. The purpose of this study was to assess acute sports injury and medical condition management decision-making skills of PTs. Methods: A Web-based survey presented 17 case scenarios related to acute medical conditions and sport injuries. PTs from the Sports Physical Therapy Section of The American Physical Therapy Association were e-mailed a cover letter/Web link to the survey and invited to participate over a 30-day period. Data were analyzed using SPSS 18.0. Results: A total of 411 of 5158 PTs who were members of the Sports Physical Therapy Association in 2009 and had valid e-mail addresses completed the survey, of which 389 (7.5%) were appropriate for analysis. Over 75.0% of respondents felt “prepared” or “somewhat prepared” to provide immediate care for 13 out of 16 medical conditions, with seizures, spinal cord injuries, and internal organ injuries having the lowest percentages. Over 75.0% of the respondents made “appropriate” or “overly cautious” decisions for 11 of the 17 acute injury or medical condition cases. Conclusions: Results of the current study indicate that PTs felt more “prepared” and tended to make “appropriate” return to play decisions on the acute sports injury and medical condition case studies more often than coaches who participated in a similar study, regardless of level of importance of the game or whether the athlete was a starter vs. non-starter. However, for PTs who plan on assisting at sporting events, additional preparation/education may be recommended, such as what is taught in an emergency responder course. PMID:21904695

Ibuprofen-associated acute kidney injury in dehydrated children with acute gastroenteritis.

PubMed

Balestracci, Alejandro; Ezquer, Mauricio; Elmo, María Eugenia; Molini, Andrea; Thorel, Claudia; Torrents, Milagros; Toledo, Ismael

2015-10-01

Non-steroidal anti-inflammatory drugs (NSAIDs) induce acute kidney injury (AKI) in volume-depleted patients; however the prevalence of this complication is likely underestimated. We assessed the impact of ibuprofen exposure on renal function among dehydrated children with acute gastroenteritis (AGE) to further characterize NSAID-associated AKI. Over a 1-year period dehydrated children with AGE (n = 105) were prospectively enrolled and grouped as cases, presenting with AKI (n = 46) or controls, not presenting with AKI (n = 59). AKI was defined by pediatric RIFLE (pRIFLE) criteria. Among the children enrolled in the study, AKI prevalence was 44 %, and 34 (54 %) of the 63 patients who received ibuprofen developed renal impairment. Relative to the controls, children presenting with AKI were younger (median age 0.66 vs. 1.74 years; p < 0.001) and received ibuprofen more frequently (74 vs. 49 %, p = 0.01). After adjusting for the degree of dehydration, ibuprofen exposure remained an independent risk factor for AKI (p < 0.001, odds ratio 2.47, 95 % confidence interval 1.78-3.42). According to the pRIFLE criteria, 17 patients were at the 'risk' stage of AKI severity, 24 were at the 'injury' stage, and five were at the 'failure' stage; none required dialysis. Distribution of patients within categories was similar regardless of ibuprofen exposure. All cases fulled recovered from AKI. Ibuprofen-associated AKI was 54 % in our cohort of dehydrated children with AGE. Drug exposure increased the risk for developing AKI by more than twofold, independent of the magnitude of the dehydration.

Contrast Medium-Induced Acute Kidney Injury

PubMed Central

Sadat, Umar; Usman, Ammara; Boyle, Jonathan R.; Hayes, Paul D.; Solomon, Richard J.

2015-01-01

Contrast medium-induced acute kidney injury (CI-AKI) is a predominant cause of hospital-acquired renal insufficiency. With an increasing number of contrast medium-enhanced radiological procedures being performed in a rapidly increasing ageing population in the Western world, it is imperative that more attention is given to understand the aetiology of CI-AKI to devise novel diagnostic methods and to formulate effective prophylactic and therapeutic regimens to reduce its incidence and its associated morbidity and mortality. This article presents high-yield information on the above-mentioned aspects of CI-AKI, primarily based on results of randomised controlled trials, meta-analyses, systematic reviews and international consensus guidelines. PMID:26195974

Strength Measurements in Acute Hamstring Injuries: Intertester Reliability and Prognostic Value of Handheld Dynamometry.

PubMed

Reurink, Gustaaf; Goudswaard, Gert Jan; Moen, Maarten H; Tol, Johannes L; Verhaar, Jan A N; Weir, Adam

2016-08-01

Study Design Cohort study, repeated measures. Background Although hamstring strength measurements are used for assessing prognosis and monitoring recovery after hamstring injury, their actual clinical relevance has not been established. Handheld dynamometry (HHD) is a commonly used method of measuring muscle strength. The reliability of HHD has not been determined in athletes with acute hamstring injuries. Objectives To determine the intertester reliability and the prognostic value of hamstring HHD strength measurement in acute hamstring injuries. Methods We measured knee flexion strength with HHD in 75 athletes at 2 visits, at baseline (within 5 days of hamstring injury) and follow-up (5 to 7 days after the baseline measurement). We assessed isometric hamstring strength in 15° and 90° of knee flexion. Reliability analysis testing was performed by 2 testers independently at the follow-up visit. We recorded the time needed to return to play (RTP) up to 6 months following baseline. Results The intraclass correlation coefficients of the strength measurements in injured hamstrings were between 0.75 and 0.83. There was a statistically significant but weak correlation between the time to RTP and the strength deficit at 15° of knee flexion measured at baseline (Spearman r = 0.25, P = .045) and at the follow-up visit (Spearman r = 0.26, P = .034). Up to 7% of the variance in time to RTP is explained by this strength deficit. None of the other strength variables were significantly correlated with time to RTP. Conclusion Hamstring strength can be reliably measured with HHD in athletes with acute hamstring injuries. The prognostic value of strength measurements is limited, as there is only a weak association between the time to RTP and hamstring strength deficit after acute injury. Level of Evidence Prognosis, level 4. J Orthop Sports Phys Ther 2016;46(8):689-696. Epub 12 May 2016. doi:10.2519/jospt.2016.6363.

Acute Kidney Injury in Pregnancy.

PubMed

Jim, Belinda; Garovic, Vesna D

2017-07-01

Pregnancy-related acute kidney injury (AKI) has declined in incidence in the last three decades, although it remains an important cause of maternal and fetal morbidity and mortality. Pregnancy-related causes of AKI such as preeclampsia, acute fatty liver of pregnancy, HELLP (Hemolysis, Elevated Liver function tests, Low Platelets) syndrome, and the thrombotic microangiopathies (thrombotic thrombocytopenic purpura, atypical hemolytic-uremic syndrome [HUS]) exhibit overlapping features and often present as diagnostic dilemmas. Differentiating among these conditions may be difficult or impossible based on clinical criteria only. In difficult and rare cases, a renal biopsy may need to be considered for the exact diagnosis and to facilitate appropriate treatment, but the risks and benefits need to be carefully weighed. The use of eculizumab for the treatment of atypical HUS has demonstrated efficacy in early case reports. Non-pregnancy related causes such as volume depletion and pyelonephritis require early and aggressive resuscitative as well as antibiotic measures respectively. We will discuss in this review the various etiologies of AKI in pregnancy, current diagnostic approaches, and the latest treatment strategies. Given the recent trends of increasing maternal age at the time of pregnancy, and the availability of modern reproductive methods increase the risks of AKI in pregnancy in the coming years. Copyright © 2017 Elsevier Inc. All rights reserved.

Acute lung injury and persistent small airway disease in a rabbit model of chlorine inhalation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Musah, Sadiatu; Schlueter, Connie F.; Humphrey, Da

Chlorine is a pulmonary toxicant to which humans can be exposed through accidents or intentional releases. Acute effects of chlorine inhalation in humans and animal models have been well characterized, but less is known about persistent effects of acute, high-level chlorine exposures. In particular, animal models that reproduce the long-term effects suggested to occur in humans are lacking. Here, we report the development of a rabbit model in which both acute and persistent effects of chlorine inhalation can be assessed. Male New Zealand White rabbits were exposed to chlorine while the lungs were mechanically ventilated. After chlorine exposure, the rabbitsmore » were extubated and were allowed to survive for up to 24 h after exposure to 800 ppm chlorine for 4 min to study acute effects or up to 7 days after exposure to 400 ppm for 8 min to study longer term effects. Acute effects observed 6 or 24 h after inhalation of 800 ppm chlorine for 4 min included hypoxemia, pulmonary edema, airway epithelial injury, inflammation, altered baseline lung mechanics, and airway hyperreactivity to inhaled methacholine. Seven days after recovery from inhalation of 400 ppm chlorine for 8 min, rabbits exhibited mild hypoxemia, increased area of pressure–volume loops, and airway hyperreactivity. Lung histology 7 days after chlorine exposure revealed abnormalities in the small airways, including inflammation and sporadic bronchiolitis obliterans lesions. Immunostaining showed a paucity of club and ciliated cells in the epithelium at these sites. These results suggest that small airway disease may be an important component of persistent respiratory abnormalities that occur following acute chlorine exposure. This non-rodent chlorine exposure model should prove useful for studying persistent effects of acute chlorine exposure and for assessing efficacy of countermeasures for chlorine-induced lung injury. - Highlights: • A novel rabbit model of chlorine-induced lung disease was

Pain thresholds and tenderness in neck and head following acute whiplash injury: a prospective study.

PubMed

Kasch, H; Stengaard-Pedersen, K; Arendt-Nielsen, L; Staehelin Jensen, T

2001-04-01

OBJECTIVE OF THE INVESTIGATION: In a 6-month prospective study of 141 consecutive acute whiplash-injured participants, and 40 acute, ankle-injured controls, pain and tenderness in the neck/head, and at a distant control site, were measured. Muscle palpation and pressure algometry in five head/neck muscle-pairs were performed after 1 week and 1, 3 and 6 months after injury. Algometry was performed at a distant control site. Whiplash-injured patients had lowered pressure-pain-detection thresholds and higher palpation-score initially in the neck/head, but the groups were similar after 6 months, and the control site was not sensitized. Focal, but not generalized, sensitization to musculoskeletal structure is present until 3 months, but not 6 months, after whiplash injury, and probably does not play a major role in the development of late whiplash syndrome. Pressure algometry and palpation are useful clinical tools in the evaluation of neck and jaw pain in acute whiplash injury.

Snake bite complicated by acute kidney injury secondary to necrotizing glomerulonephritis.

PubMed

Al Qahtani, Mohammad A; Altheaby, Abdulrahman; Al Anazi, T; Al Saad, Khaled; Binsalih, S; Al Helail, Mohammed

2014-11-01

We present a 38-year-old man who presented to the emergency department with complaints of a snake bite. He developed acute kidney injury (AKI) and the kidney biopsy showed necrotizing glomerulonephritis, which is rarely reported in AKI after snake bite.

The effects of contrast media volume on acute kidney injury after transcatheter aortic valve replacement: a systematic review and meta-analysis.

PubMed

Thongprayoon, Charat; Cheungpasitporn, Wisit; Podboy, Alexander J; Gillaspie, Erin A; Greason, Kevin L; Kashani, Kianoush B

2016-11-01

The goal of this systematic review was to assess the effects of contrast media volume on transcatheter aortic valve replacement-related acute kidney injury. A literature search was performed using Medline, EMbase, the Cochrane Database of Systematic Reviews, and clinicaltrials.gov from the inception of these databases through December 2015. Studies that reported relative risk, odds ratio, or hazard ratio comparing the risks of acute kidney injury following transcatheter aortic valve replacement in patients who received high contrast media volume were included. Pooled risk ratio (RR) and 95% confidence intervals (95% CI) were calculated using a random-effect, generic inverse variance method. Four cohort studies composed of 891 patients were included in the analyses to assess the risk of acute kidney injury after transcatheter aortic valve replacement in patients who received high contrast media volume. The pooled RR of acute kidney injury after transcatheter aortic valve replacement in patients who received a large volume of contrast media was 1.41 (95% CI, 0.87 to 2.28) compared with low contrast media volume. The meta-analysis was limited to studies using standard acute kidney injury definitions, and the pooled RR of acute kidney injury in patients who received high contrast media volume is 1.12 (95% CI, 0.78 to 1.62). Our meta-analysis shows no significant association between contrast media volume and risk of acute kidney injury after transcatheter aortic valve replacement. © 2016 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.

Acute liver injury associated with a newer formulation of the herbal weight loss supplement Hydroxycut

PubMed Central

Worman, Howard J

2015-01-01

Despite the widespread use of herbal and dietary supplements (HDS), serious cases of hepatotoxicity have been reported. The popular herbal weight loss supplement, Hydroxycut, has previously been implicated in acute liver injury. Since its introduction, Hydroxycut has undergone successive transformations in its formulation; yet, cases of liver injury have remained an ongoing problem. We report a case of a 41-year-old Hispanic man who developed acute hepatocellular liver injury with associated nausea, vomiting, jaundice, fatigue and asterixis attributed to the use of a newer formulation of Hydroxycut, SX-7 Clean Sensory. The patient required hospitalisation and improved with supportive therapy. Despite successive transformations in its formulation, potential liver injury appears to remain an ongoing problem with Hydroxycut. Our case illustrates the importance of obtaining a thorough medication history, including HDS, regardless of new or reformulated product marketing efforts. PMID:25948859

Dance floors as injury risk: analysis and evaluation of acute injuries caused by dance floors in professional dance with regard to preventative aspects.

PubMed

Wanke, Eileen M; Mill, Helmgard; Wanke, Alice; Davenport, Jaqueline; Koch, Franziska; Groneberg, David A

2012-09-01

A dance floor is often the only support of movements in dance. A dance floor surface that shows deficiencies, can result in acute injuries and chronic problems. Although the significance of an adequate dance floor is well known, there is still a lack of differentiated analyses of dance floor-related acute injuries. This study presents data on acute injuries exclusively caused by the dance floor. The data were obtained from standardized work accident reports from consultants (F 1000), documentary accident records from all Berlin theatres, a state ballet school (n=2,281), and case records from the Berlin State Accident Insurance (UKB) covering a period of 17 years. All analyses and descriptive statistics were conducted with Excel 2007 and SPSS 18. Dance floor surfaces were the causative factor in 12.8% of all accidents (n=291, female 183, male 108). Almost two thirds (62.6%) of all accidents in professional dancers happened on stage, and almost half (49.5%) occurred during performances. As for causative factors, 53.1% of the professional dancers (P) and 42.5% of the dance students (S) claimed that the floor had been "too slippery," with "getting stuck" or (tripping) as the second most common problem (P 18.4%, S 11.3%). Of the injured dancers, 41.8% were older than 30 years and can therefore be categorized as experienced. Dance floors play a significant role in the occurrence of acute injuries, even in experienced dancers. Performances on stage seem to be a particular risk. However, injury prevention measures should include all work locations (P) as well as non-dance-specific locations (S).

Protective role of testosterone in ischemia-reperfusion-induced acute kidney injury

PubMed Central

Soljancic, Andrea; Ruiz, Arnaldo Lopez; Chandrashekar, Kiran; Maranon, Rodrigo; Liu, Ruisheng; Juncos, Luis A.

2013-01-01

Men are at greater risk for renal injury and dysfunction after acute ischemia-reperfusion (I/R) than are women. Studies in animals suggest that the reason for the sex difference in renal injury and dysfunction after I/R is the protective effect of estrogens in females. However, a reduction in testosterone in men is thought to play an important role in mediating cardiovascular and renal disease, in general. In the present study, we tested the hypothesis that I/R of the kidney reduces serum testosterone, and that contributes to renal dysfunction and injury. Male rats that were subjected to renal ischemia of 40 min followed by reperfusion had a 90% reduction in serum testosterone by 3 h after reperfusion that remained at 24 h. Acute infusion of testosterone 3 h after reperfusion attenuated the increase in plasma creatinine and urinary kidney injury molecule-1 (KIM-1) at 24 h, prevented the reduction in outer medullary blood flow, and attenuated the increase in intrarenal TNF-α and the decrease in intrarenal VEGF at 48 h. Castration of males caused greater increases in plasma creatinine and KIM-1 at 24 h than in intact males with renal I/R, and treatment with anastrozole, an aromatase inhibitor, plus testosterone almost normalized plasma creatinine and KIM-1 in rats with renal I/R. These data show that renal I/R is associated with sustained reductions in testosterone, that testosterone repletion protects the kidney, whereas castration promotes renal dysfunction and injury, and that the testosterone-mediated protection is not conferred by conversion to estradiol. PMID:23552495

Investigating Metacognition, Cognition, and Behavioral Deficits of College Students with Acute Traumatic Brain Injuries

ERIC Educational Resources Information Center

Martinez, Sarah; Davalos, Deana

2016-01-01

Objective: Executive dysfunction in college students who have had an acute traumatic brain injury (TBI) was investigated. The cognitive, behavioral, and metacognitive effects on college students who endorsed experiencing a brain injury were specifically explored. Participants: Participants were 121 college students who endorsed a mild TBI, and 121…

Acute injuries in soccer, ice hockey, volleyball, basketball, judo, and karate: analysis of national registry data.

PubMed Central

Kujala, U. M.; Taimela, S.; Antti-Poika, I.; Orava, S.; Tuominen, R.; Myllynen, P.

1995-01-01

OBJECTIVE--To determine the acute injury profile in each of six sports and compare the injury rates between the sports. DESIGN--Analysis of national sports injury insurance registry data. SETTING--Finland during 1987-91. SUBJECTS--621,691 person years of exposure among participants in soccer, ice hockey, volleyball, basketball, judo, or karate. MAIN OUTCOME MEASURES--Acute sports injuries requiring medical treatment and reported to the insurance company on structured forms by the patients and their doctors. RESULTS--54,186 sports injuries were recorded. Injury rates were low in athletes aged under 15, while 20-24 year olds had the highest rates. Differences in injury rates between the sports were minor in this adult age group. Overall injury rates were higher in sports entailing more frequent and powerful body contact. Each sport had a specific injury profile. Fractures and dental injuries were most common in ice hockey and karate and least frequent in volleyball. Knee injuries were the most common cause of permanent disability. CONCLUSIONS--Based on the defined injury profiles in the different sports it is recommended that sports specific preventive measures should be employed to decrease the number of violent contacts between athletes, including improved game rules supported by careful refereeing. To prevent dental injuries the wearing of mouth guards should be encouraged, especially in ice hockey, karate, and basketball. PMID:8520333

Physical complications in acute lung injury survivors: a two-year longitudinal prospective study.

PubMed

Fan, Eddy; Dowdy, David W; Colantuoni, Elizabeth; Mendez-Tellez, Pedro A; Sevransky, Jonathan E; Shanholtz, Carl; Himmelfarb, Cheryl R Dennison; Desai, Sanjay V; Ciesla, Nancy; Herridge, Margaret S; Pronovost, Peter J; Needham, Dale M

2014-04-01

Survivors of severe critical illness frequently develop substantial and persistent physical complications, including muscle weakness, impaired physical function, and decreased health-related quality of life. Our objective was to determine the longitudinal epidemiology of muscle weakness, physical function, and health-related quality of life and their associations with critical illness and ICU exposures. A multisite prospective study with longitudinal follow-up at 3, 6, 12, and 24 months after acute lung injury. Thirteen ICUs from four academic teaching hospitals. Two hundred twenty-two survivors of acute lung injury. None. At each time point, patients underwent standardized clinical evaluations of extremity, hand grip, and respiratory muscle strength; anthropometrics (height, weight, mid-arm circumference, and triceps skin fold thickness); 6-minute walk distance, and the Medical Outcomes Short-Form 36 health-related quality of life survey. During their hospitalization, survivors also had detailed daily evaluation of critical illness and related treatment variables. Over one third of survivors had objective evidence of muscle weakness at hospital discharge, with most improving within 12 months. This weakness was associated with substantial impairments in physical function and health-related quality of life that persisted at 24 months. The duration of bed rest during critical illness was consistently associated with weakness throughout 24-month follow-up. The cumulative dose of systematic corticosteroids and use of neuromuscular blockers in the ICU were not associated with weakness. Muscle weakness is common after acute lung injury, usually recovering within 12 months. This weakness is associated with substantial impairments in physical function and health-related quality of life that continue beyond 24 months. These results provide valuable prognostic information regarding physical recovery after acute lung injury. Evidence-based methods to reduce the duration of

Intra- and interrater reliability of three different MRI grading and classification systems after acute hamstring injuries.

PubMed

Wangensteen, Arnlaug; Tol, Johannes L; Roemer, Frank W; Bahr, Roald; Dijkstra, H Paul; Crema, Michel D; Farooq, Abdulaziz; Guermazi, Ali

2017-04-01

To assess and compare the intra- and interrater reliability of three different MRI grading and classification systems after acute hamstring injury. Male athletes (n=40) with clinical diagnosis of acute hamstring injury and MRI ≤5days were selected from a prospective cohort. Two radiologists independently evaluated the MRIs using standardised scoring form including the modified Peetrons grading system, the Chan acute muscle strain injury classification and the British Athletics Muscle Injury Classification. Intra-and interrater reliability was assessed with linear weighted kappa (κ) or unweighted Cohen's κ and percentage agreement was calculated. We observed 'substantial' to 'almost perfect' intra- (κ range 0.65-1.00) and interrater reliability (κ range 0.77-1.00) with percentage agreement 83-100% and 88-100%, respectively, for severity gradings, overall anatomical sites and overall classifications for the three MRI systems. We observed substantial variability (κ range -0.05 to 1.00) for subcategories within the Chan classification and the British Athletics Muscle Injury Classification, however, the prevalence of positive scorings was low for some subcategories. The modified Peetrons grading system, overall Chan classification and overall British Athletics Muscle Injury Classification demonstrated 'substantial' to 'almost perfect' intra- and interrater reliability when scored by experienced radiologists. The intra- and interrater reliability for the anatomical subcategories within the classifications remains unclear. Copyright © 2017 Elsevier B.V. All rights reserved.

Lung protective mechanical ventilation and two year survival in patients with acute lung injury: prospective cohort study

PubMed Central

Colantuoni, Elizabeth; Mendez-Tellez, Pedro A; Dinglas, Victor D; Sevransky, Jonathan E; Dennison Himmelfarb, Cheryl R; Desai, Sanjay V; Shanholtz, Carl; Brower, Roy G; Pronovost, Peter J

2012-01-01

Objective To evaluate the association of volume limited and pressure limited (lung protective) mechanical ventilation with two year survival in patients with acute lung injury. Design Prospective cohort study. Setting 13 intensive care units at four hospitals in Baltimore, Maryland, USA. Participants 485 consecutive mechanically ventilated patients with acute lung injury. Main outcome measure Two year survival after onset of acute lung injury. Results 485 patients contributed data for 6240 eligible ventilator settings, as measured twice daily (median of eight eligible ventilator settings per patient; 41% of which adhered to lung protective ventilation). Of these patients, 311 (64%) died within two years. After adjusting for the total duration of ventilation and other relevant covariates, each additional ventilator setting adherent to lung protective ventilation was associated with a 3% decrease in the risk of mortality over two years (hazard ratio 0.97, 95% confidence interval 0.95 to 0.99, P=0.002). Compared with no adherence, the estimated absolute risk reduction in two year mortality for a prototypical patient with 50% adherence to lung protective ventilation was 4.0% (0.8% to 7.2%, P=0.012) and with 100% adherence was 7.8% (1.6% to 14.0%, P=0.011). Conclusions Lung protective mechanical ventilation was associated with a substantial long term survival benefit for patients with acute lung injury. Greater use of lung protective ventilation in routine clinical practice could reduce long term mortality in patients with acute lung injury. Trial registration Clinicaltrials.gov NCT00300248. PMID:22491953

CE: Preventing Contrast-Induced Acute Kidney Injury.

PubMed

Gallegos, Yvonne; Taha, Asma Ali; Rutledge, Dana N

2016-12-01

: Diagnostic radiographic imaging scans using intravascular iodinated contrast media can lead to various complications. The most salient of these is contrast-induced acute kidney injury (CI-AKI) or contrast-induced nephropathy, a potentially costly and serious patient safety concern. Prevention strategies are the cornerstone of evidence-based clinical management for patients receiving contrast agents. These include preprocedure screening, stratification of patients based on risk factors, and protective interventions, the most important of which is hydration both before and after the radiographic imaging scan. There is a gap, however, between best evidence and clinical practice in terms of exact hydration protocols. Nurses play an important role in nephropathy prevention and need to be familiar with CI-AKI as a potential complication of radiographic imaging scans. In order to ensure safe, high-quality care, nurses must be involved in efforts to prevent CI-AKI as well as interventions that minimize patients' risk of kidney injury.

Biological markers of stress in pediatric acute burn injury.

PubMed

Brown, Nadia J; Kimble, Roy M; Rodger, Sylvia; Ware, Robert S; McWhinney, Brett C; Ungerer, Jacobus P J; Cuttle, Leila

2014-08-01

Burns and their associated wound care procedures evoke significant stress and anxiety, particularly for children. Little is known about the body's physiological stress reactions throughout the stages of re-epithelialization following an acute burn injury. Previously, serum and urinary cortisol have been used to measure stress in burn patients, however these measures are not suitable for a pediatric burn outpatient setting. To assess the sensitivity of salivary cortisol and sAA in detecting stress during acute burn wound care procedures and to investigate the body's physiological stress reactions throughout burn re-epithelialization. Seventy-seven participants aged four to thirteen years who presented with an acute burn injury to the burn center at the Royal Children's Hospital, Brisbane, Australia, were recruited between August 2011 and August 2012. Both biomarkers were responsive to the stress of burn wound care procedures. sAA levels were on average 50.2 U/ml higher (p<0.001) at 10 min post-dressing removal compared to baseline levels. Salivary cortisol levels showed a blunted effect with average levels at ten minutes post dressing removal decreasing by 0.54 nmol/L (p<0.001) compared to baseline levels. sAA levels were associated with pain (p=0.021), no medication (p=0.047) and Child Trauma Screening Questionnaire scores at three months post re-epithelialization (p=0.008). Similarly, salivary cortisol was associated with no medication (p<0.001), pain scores (p=0.045) and total body surface area of the burn (p=0.010). Factors which support the use of sAA over salivary cortisol to assess stress during morning acute burn wound care procedures include; sensitivity, morning clinic times relative to cortisol's diurnal peaks, and relative cost. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

Spikes in acute workload are associated with increased injury risk in elite cricket fast bowlers.

PubMed

Hulin, Billy T; Gabbett, Tim J; Blanch, Peter; Chapman, Paul; Bailey, David; Orchard, John W

2014-04-01

To determine if the comparison of acute and chronic workload is associated with increased injury risk in elite cricket fast bowlers. Data were collected from 28 fast bowlers who completed a total of 43 individual seasons over a 6-year period. Workloads were estimated by summarising the total number of balls bowled per week (external workload), and by multiplying the session rating of perceived exertion by the session duration (internal workload). One-week data (acute workload), together with 4-week rolling average data (chronic workload), were calculated for external and internal workloads. The size of the acute workload in relation to the chronic workload provided either a negative or positive training-stress balance. A negative training-stress balance was associated with an increased risk of injury in the week after exposure, for internal workload (relative risk (RR)=2.2 (CI 1.91 to 2.53), p=0.009), and external workload (RR=2.1 (CI 1.81 to 2.44), p=0.01). Fast bowlers with an internal workload training-stress balance of greater than 200% had a RR of injury of 4.5 (CI 3.43 to 5.90, p=0.009) compared with those with a training-stress balance between 50% and 99%. Fast bowlers with an external workload training-stress balance of more than 200% had a RR of injury of 3.3 (CI 1.50 to 7.25, p=0.033) in comparison to fast bowlers with an external workload training-stress balance between 50% and 99%. These findings demonstrate that large increases in acute workload are associated with increased injury risk in elite cricket fast bowlers.

Emphysema induced by elastase alters the mRNA relative levels from DNA repair genes in acute lung injury in response to sepsis induced by lipopolysaccharide administration in Wistar rats.

PubMed

Sergio, Luiz Philippe S; Lucinda, Leda M F; Reboredo, Maycon M; de Paoli, Flavia; Fonseca, Lídia M C; Pinheiro, Bruno V; Mencalha, Andre L; Fonseca, Adenilson S

2018-03-01

Purpose/Aim of the study: Patients suffering from chronic obstructive pulmonary disease (COPD) in association with acute respiratory distress syndrome (ARDS) present oxidative stress in lung cells, with production of free radicals and DNA lesions in pulmonary and adjacent cells. Once the DNA molecule is damaged, a set of enzymatic mechanisms are trigged to preserve genetic code integrity and cellular homeostasis. These enzymatic mechanisms include the base and the nucleotide excision repair pathways, as well as telomere regulation. Thus, the aim of this work was to evaluate the mRNA levels from APEX1, ERCC2, TP53, and TRF2 genes in lung tissue from Wistar rats affected by acute lung injury in response to sepsis and emphysema. Adult male Wistar rats were randomized into 4 groups (n = 6, for each group): control, emphysema, sepsis, and emphysema with sepsis. Pulmonary emphysema was induced by intratracheal instillation of elastase (12 IU/animal) and sepsis induced by intraperitoneal Escherichia coli lipopolysaccharide (LPS) injection (10 mg/kg). Lungs were removed, and samples were withdrawn for histological analysis and total RNA extraction, cDNA synthesis, and mRNA level evaluation by real time quantitative polymerase chain reaction. Data show acute lung injury by LPS and emphysema by elastase and that APEX1, ERCC2, TP53, and TRF2 mRNA levels are increased significantly (p < 0.01) in emphysema with sepsis group. Our results suggest that alteration in mRNA levels from DNA repair and genomic stability could be part of cell response to acute lung injury in response to emphysema and sepsis.

Augmenter of liver regeneration protects against carbon tetrachloride-induced liver injury by promoting autophagy in mice

PubMed Central

Shi, Hongbo; Han, Weijia; Shi, Honglin; Ren, Feng; Chen, Dexi; Chen, Yu; Duan, Zhongping

2017-01-01

Background Augmenter of liver regeneration (ALR) exerts strong hepatoprotective properties in various animal models of liver injury, but its protective mechanisms have not yet been explored. Autophagy is a recently recognized rudimentary cellular response to inflammation and injury. The aim of this study was to test the hypothesis that ALR may protect against acute liver injury through the autophagic pathway. Methods The level and role of ALR in liver injury were studied in a mouse model of acute liver injury induced by carbon tetrachloride (CCl4). The effect of ALR on autophagy was analyzed in vitro and in vivo. After autophagy was inhibited by 3-methyladenine (3-MA), apoptosis and proliferation were detected in the mouse model with acute liver injury. The ALR and autophagic levels were measured in patients with liver cirrhosis (LC) and acute liver failure (ALF), respectively. Results During the progression of acute liver injury, the ALR levels increased slightly in early stage and significantly decreased in late stage in mice Treatment with an ALR plasmid via tail vein injection protected mice against acute liver injury. The protective effect of ALR relied on the induction of autophagy, which was supported by the following evidence: (1) ALR overexpression directly induced autophagy flux in vitro and in vivo; and (2) ALR treatment suppressed apoptosis and promoted proliferation in mice exposed to CCl4, but the inhibition of autophagy reversed these effects. More importantly, the ALR levels decreased in patients with LC and ALF compared with normal controls. Conclusion We demonstrated that ALR ameliorated liver injury via an autophagic mechanism, which indicates a potential therapeutic application for liver injury. PMID:28061452

Tubular Recovery after Acute Kidney Injury.

PubMed

Fattah, Hadi; Vallon, Volker

2018-05-31

A significant portion of patients who are affected by acute kidney injury (AKI) do not fully recover due to largely unclear reasons. Restoration of tubular function has been proposed to be a prerequisite for glomerular filtration rate (GFR) recovery. Proximal tubular cells dedifferentiate during the tubular injury phase, which is required for subsequent cell proliferation and replacement of lost epithelial cells. Experimental studies indicate that some cells fail to redifferentiate and continue to produce growth factors (e.g., transforming growth factor β) that can induce fibrosis. Preclinical studies provide first evidence for beneficial effects of inhibiting glucose transport in the proximal tubule in models of ischemia-reperfusion injury. Comparing renal RNA sequencing data with kidney function during recovery from varying levels of AKI may provide new cues with regard to the sequence of events and help identify key determinants of recovery from AKI. Key Messages: Tubular recovery after AKI is vital for recovery of kidney function including improvement of GFR, and likely determines which patients fully recover from AKI or progress to chronic kidney disease. There is a need to better understand the sequence of events and the processes of tubular cell proliferation and repair, including safe strategies to intervene. The temporary inhibition of selected tubular transport processes, possibly in selected nephron regions, may provide an opportunity to improve tubular cell energetics and facilitate tubular cell recovery with consequences for kidney outcome. © 2018 S. Karger AG, Basel.

Application of small RNA sequencing to identify microRNAs in acute kidney injury and fibrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pellegrini, Kathryn L.

Establishing a microRNA (miRNA) expression profile in affected tissues provides an important foundation for the discovery of miRNAs involved in the development or progression of pathologic conditions. We conducted small RNA sequencing to generate a temporal profile of miRNA expression in the kidneys using a mouse model of folic acid-induced (250 mg/kg i.p.) kidney injury and fibrosis. From the 103 miRNAs that were differentially expressed over the time course (> 2-fold, p < 0.05), we chose to further investigate miR-18a-5p, which is expressed during the acute stage of the injury; miR-132-3p, which is upregulated during transition between acute and fibroticmore » injury; and miR-146b-5p, which is highly expressed at the peak of fibrosis. Using qRT-PCR, we confirmed the increased expression of these candidate miRNAs in the folic acid model as well as in other established mouse models of acute injury (ischemia/reperfusion injury) and fibrosis (unilateral ureteral obstruction). In situ hybridization confirmed high expression of miR-18a-5p, miR-132-3p and miR-146b-5p throughout the kidney cortex in mice and humans with severe kidney injury or fibrosis. When primary human proximal tubular epithelial cells were treated with model nephrotoxicants such as cadmium chloride (CdCl{sub 2}), arsenic trioxide, aristolochic acid (AA), potassium dichromate (K{sub 2}Cr{sub 2}O{sub 7}) and cisplatin, miRNA-132-3p was upregulated 4.3-fold after AA treatment and 1.5-fold after K{sub 2}Cr{sub 2}O{sub 7} and CdCl{sub 2} treatment. These results demonstrate the application of temporal small RNA sequencing to identify miR-18a, miR-132 and miR-146b as differentially expressed miRNAs during distinct phases of kidney injury and fibrosis progression. - Highlights: • We used small RNA sequencing to identify differentially expressed miRNAs in kidney. • Distinct patterns were found for acute injury and fibrotic stages in the kidney. • Upregulation of miR-18a, -132 and -146b was confirmed

Cardiac function in an endothermic fish: cellular mechanisms for overcoming acute thermal challenges during diving

PubMed Central

Shiels, H. A.; Galli, G. L. J.; Block, B. A.

2015-01-01

Understanding the physiology of vertebrate thermal tolerance is critical for predicting how animals respond to climate change. Pacific bluefin tuna experience a wide range of ambient sea temperatures and occupy the largest geographical niche of all tunas. Their capacity to endure thermal challenge is due in part to enhanced expression and activity of key proteins involved in cardiac excitation–contraction coupling, which improve cardiomyocyte function and whole animal performance during temperature change. To define the cellular mechanisms that enable bluefin tuna hearts to function during acute temperature change, we investigated the performance of freshly isolated ventricular myocytes using confocal microscopy and electrophysiology. We demonstrate that acute cooling and warming (between 8 and 28°C) modulates the excitability of the cardiomyocyte by altering the action potential (AP) duration and the amplitude and kinetics of the cellular Ca2+ transient. We then explored the interactions between temperature, adrenergic stimulation and contraction frequency, and show that when these stressors are combined in a physiologically relevant way, they alter AP characteristics to stabilize excitation–contraction coupling across an acute 20°C temperature range. This allows the tuna heart to maintain consistent contraction and relaxation cycles during acute thermal challenges. We hypothesize that this cardiac capacity plays a key role in the bluefin tunas' niche expansion across a broad thermal and geographical range. PMID:25540278

Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury.

PubMed

Nickolas, Thomas L; O'Rourke, Matthew J; Yang, Jun; Sise, Meghan E; Canetta, Pietro A; Barasch, Nicholas; Buchen, Charles; Khan, Faris; Mori, Kiyoshi; Giglio, James; Devarajan, Prasad; Barasch, Jonathan

2008-06-03

A single serum creatinine measurement cannot distinguish acute kidney injury from chronic kidney disease or prerenal azotemia. To test the sensitivity and specificity of a single measurement of urinary neutrophil gelatinase-associated lipocalin (NGAL) and other urinary proteins to detect acute kidney injury in a spectrum of patients. Prospective cohort study. Emergency department of Columbia University Medical Center, New York, New York. 635 patients admitted to the hospital with acute kidney injury, prerenal azotemia, chronic kidney disease, or normal kidney function. Diagnosis of acute kidney injury was based on the RIFLE (risk, injury, failure, loss, and end-stage) criteria and assigned by researchers who were blinded to experimental measurements. Urinary NGAL was measured by immunoblot, N-acetyl-beta-d-glucosaminidase (NAG) by enzyme measurement, alpha1-microglobulin and alpha(1)-acid glycoprotein by immunonephelometry, and serum creatinine by Jaffe kinetic reaction. Experimental measurements were not available to treating physicians. Patients with acute kidney injury had a significantly elevated mean urinary NGAL level compared with the other kidney function groups (416 microg/g creatinine [SD, 387]; P = 0.001). At a cutoff value of 130 microg/g creatinine, sensitivity and specificity of NGAL for detecting acute injury were 0.900 (95% CI, 0.73 to 0.98) and 0.995 (CI, 0.990 to 1.00), respectively, and positive and negative likelihood ratios were 181.5 (CI, 58.33 to 564.71) and 0.10 (CI, 0.03 to 0.29); these values were superior to those for NAG, alpha1-microglobulin, alpha1-acid glycoprotein, fractional excretion of sodium, and serum creatinine. In multiple logistic regression, urinary NGAL level was highly predictive of clinical outcomes, including nephrology consultation, dialysis, and admission to the intensive care unit (odds ratio, 24.71 [CI, 7.69 to 79.42]). All patients came from a single center. Few kidney biopsies were performed. A single measurement

Ischemic preconditioning provides both acute and delayed protection against renal ischemia and reperfusion injury in mice.

PubMed

Joo, Jin Deok; Kim, Mihwa; D'Agati, Vivette D; Lee, H Thomas

2006-11-01

Acute as well as delayed ischemic preconditioning (IPC) provides protection against cardiac and neuronal ischemia reperfusion (IR) injury. This study determined whether delayed preconditioning occurs in the kidney and further elucidated the mechanisms of renal IPC in mice. Mice were subjected to IPC (four cycles of 5 min of ischemia and reperfusion) and then to 30 min of renal ischemia either 15 min (acute IPC) or 24 h (delayed IPC) later. Both acute and delayed renal IPC provided powerful protection against renal IR injury. Inhibition of Akt but not extracellular signal-regulated kinase phosphorylation prevented the protection that was afforded by acute IPC. Neither extracellular signal-regulated kinase nor Akt inhibition prevented protection that was afforded by delayed renal IPC. Pretreatment with an antioxidant, N-(2-mercaptopropionyl)-glycine, to scavenge free radicals prevented the protection that was provided by acute but not delayed renal IPC. Inhibition of protein kinase C or pertussis toxin-sensitive G-proteins attenuated protection from both acute and delayed renal IPC. Delayed renal IPC increased inducible nitric oxide synthase (iNOS) as well as heat-shock protein 27 synthesis, and the renal protective effects of delayed preconditioning were attenuated by a selective inhibitor of iNOS (l-N(6)[1-iminoethyl]lysine). Moreover, delayed IPC was not observed in iNOS knockout mice. Both acute and delayed IPC were independent of A(1) adenosine receptors (AR) as a selective A(1)AR antagonist failed to block preconditioning and acute and delayed preconditioning occurred in mice that lacked A(1)AR. Therefore, this study demonstrated that acute or delayed IPC provides renal protection against IR injury in mice but involves distinct signaling pathways.

Heat stroke leading to acute liver injury & failure: A case series from the Acute Liver Failure Study Group.

PubMed

Davis, Brian C; Tillman, Holly; Chung, Raymond T; Stravitz, Richard T; Reddy, Rajender; Fontana, Robert J; McGuire, Brendan; Davern, Timothy; Lee, William M

2017-04-01

In the United States, nearly 1000 annual cases of heat stroke are reported but the frequency and outcome of severe liver injury in such patients is not well described. The aim of this study was to describe cases of acute liver injury (ALI) or failure (ALF) caused by heat stroke in a large ALF registry. Amongst 2675 consecutive subjects enrolled in a prospective observational cohort of patients with ALI or ALF between January 1998 and April 2015, there were eight subjects with heat stroke. Five patients had ALF and three had ALI. Seven patients developed acute kidney injury, all eight had lactic acidosis and rhabdomyolysis. Six patients underwent cooling treatments, three received N-acetyl cysteine (NAC), three required mechanical ventilation, three required renal replacement therapy, two received vasopressors, one underwent liver transplantation, and two patients died-both within 48 hours of presentation. All cases occurred between May and August, mainly in healthy young men because of excessive exertion. Management of ALI and ALF secondary to heat stroke should focus on cooling protocols and supportive care, with consideration of liver transplantation in refractory patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acute liver injury associated with a newer formulation of the herbal weight loss supplement Hydroxycut.

PubMed

Araujo, James L; Worman, Howard J

2015-05-06

Despite the widespread use of herbal and dietary supplements (HDS), serious cases of hepatotoxicity have been reported. The popular herbal weight loss supplement, Hydroxycut, has previously been implicated in acute liver injury. Since its introduction, Hydroxycut has undergone successive transformations in its formulation; yet, cases of liver injury have remained an ongoing problem. We report a case of a 41-year-old Hispanic man who developed acute hepatocellular liver injury with associated nausea, vomiting, jaundice, fatigue and asterixis attributed to the use of a newer formulation of Hydroxycut, SX-7 Clean Sensory. The patient required hospitalisation and improved with supportive therapy. Despite successive transformations in its formulation, potential liver injury appears to remain an ongoing problem with Hydroxycut. Our case illustrates the importance of obtaining a thorough medication history, including HDS, regardless of new or reformulated product marketing efforts. 2015 BMJ Publishing Group Ltd.

Acute Gonadotroph and Somatotroph Hormonal Suppression after Traumatic Brain Injury

PubMed Central

Wagner, Justin; Dusick, Joshua R.; McArthur, David L.; Cohan, Pejman; Wang, Christina; Swerdloff, Ronald; Boscardin, W. John

2010-01-01

Abstract Hormonal dysfunction is a known consequence of moderate and severe traumatic brain injury (TBI). In this study we determined the incidence, time course, and clinical correlates of acute post-TBI gonadotroph and somatotroph dysfunction. Patients had daily measurement of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, estradiol, growth hormone, and insulin-like growth factor-1 (IGF-1) for up to 10 days post-injury. Values below the fifth percentile of a healthy cohort were considered abnormal, as were non-measurable growth hormone (GH) values. Outcome measures were frequency and time course of hormonal suppression, injury characteristics, and Glasgow Outcome Scale (GOS) score. The cohort consisted of 101 patients (82% males; mean age 35 years; Glasgow Coma Scale [GCS] score ≤8 in 87%). In men, 100% had at least one low testosterone value, and 93% of all values were low; in premenopausal women, 43% had at least one low estradiol value, and 39% of all values were low. Non-measurable GH levels occurred in 38% of patients, while low IGF-1 levels were observed in 77% of patients, but tended to normalize within 10 days. Multivariate analysis revealed associations of younger age with low FSH and low IGF-1, acute anemia with low IGF-1, and older age and higher body mass index (BMI) with low GH. Hormonal suppression was not predictive of GOS score. These results indicate that within 10 days of complicated mild, moderate, and severe TBI, testosterone suppression occurs in all men and estrogen suppression occurs in over 40% of women. Transient somatotroph suppression occurs in over 75% of patients. Although this acute neuroendocrine dysfunction may not be TBI-specific, low gonadal steroids, IGF-1, and GH may be important given their putative neuroprotective functions. PMID:20214417

A Double-Blinded, Randomized, Placebo-Controlled Clinical Trial of Aminophylline to Prevent Acute Kidney Injury in Children Following Congenital Heart Surgery With Cardiopulmonary Bypass.

PubMed

Axelrod, David M; Sutherland, Scott M; Anglemyer, Andrew; Grimm, Paul C; Roth, Stephen J

2016-02-01

Acute kidney injury occurs commonly in children following congenital cardiac surgery with cardiopulmonary bypass and has been associated with increased morbidity and mortality. Aminophylline, a methylxanthine nonselective adenosine receptor antagonist, has been effective in the management of acute kidney injury in certain populations. This study sought to determine whether postoperative administration of aminophylline attenuates acute kidney injury in children undergoing congenital cardiac surgery with cardiopulmonary bypass. Single-center, double-blinded, placebo-controlled, randomized clinical trial. Tertiary center, pediatric cardiovascular ICU. A total of 144 children after congenital heart surgery with cardiopulmonary bypass. Seventy-two patients were randomized to receive aminophylline and 72 patients received placebo. Study drug was administered every 6 hours for 72 hours. The primary outcome variable was the development of any acute kidney injury, defined by the serum creatinine criteria of the Kidney Diseases: Improving Global Outcomes. Secondary outcomes included the development of severe acute kidney injury, time between cardiovascular ICU admission and first successful extubation, percent fluid overload, total fluid balance, urine output, bioelectrical impedance, and serum neutrophil gelatinase-associated lipocalin. The unadjusted rate and severity of acute kidney injury were not different between groups; 43 of 72 (60%) of the treatment group and 36 of 72 (50%) of the placebo group developed acute kidney injury (p = 0.32). Stage 2/3 acute kidney injury occurred in 23 of 72 (32%) of the treatment group and 15 of 72 (21%) of the placebo group (p = 0.18). Secondary outcome measures also demonstrated no significant difference between treatment and placebo groups. Aminophylline administration was safe; no deaths occurred in either group, and rates of adverse events were similar (14% in the treatment group vs 18% in the placebo group; p = 0.30). In this

Acute hyperglycaemia enhances oxidative stress and aggravates myocardial ischaemia/reperfusion injury: role of thioredoxin-interacting protein

PubMed Central

Su, Hui; Ji, Lele; Xing, Wenjuan; Zhang, Wei; Zhou, Heping; Qian, Xinhong; Wang, Xiaoming; Gao, Feng; Sun, Xin; Zhang, Haifeng

2013-01-01

Hyperglycaemia during acute myocardial infarction is common and associated with increased mortality. Thioredoxin-interacting protein (Txnip) is a modulator of cellular redox state and contributes to cell apoptosis. This study aimed to investigate whether or not hyperglycaemia enhances Txnip expression in myocardial ischaemia/reperfusion (MI/R) and consequently exacerbates MI/R injury. Rats were subjected to 30 min. of left coronary artery ligation followed by 4 hrs of reperfusion and treated with saline or high glucose (HG, 500 g/l, 4 ml/kg/h intravenously). In vitro study was performed on cultured rat cardiomyocytes subjected to simulated ischaemia/reperfusion (SI/R) and incubated with HG (25 mM) or normal glucose (5.6 mM) medium. In vivo HG infusion during MI/R significantly impaired cardiac function, aggravated myocardial injury and increased cardiac oxidative stress. Meanwhile, Txnip expression was enhanced whereas thioredoxin activity was inhibited following HG treatment in ischaemia/reperfusion (I/R) hearts. In addition, HG activated p38 MAPK and inhibited Akt in I/R hearts. In cultured cardiomyocytes subjected to SI/R, HG incubation stimulated Txnip expression and reduced thioredoxin activity. Overexpression of Txnip enhanced HG-induced superoxide generation and aggravated cardiomyocyte apoptosis, whereas Txnip RNAi significantly blunted the deleterious effects of HG. Moreover, inhibition of p38 MAPK or activation of Akt markedly blocked HG-induced Txnip expression in I/R cardiomyocytes. Most importantly, intramyocardial injection of Txnip siRNA markedly decreased Txnip expression and alleviated MI/R injury in HG-treated rats. Hyperglycaemia enhances myocardial Txnip expression, possibly through reciprocally modulating p38 MAPK and Akt activation, leading to aggravated oxidative stress and subsequently, amplification of cardiac injury following MI/R. PMID:23305039

Predictors of poor outcomes in patients with wild mushroom-induced acute liver injury.

PubMed

Kim, Taerim; Lee, Danbi; Lee, Jae Ho; Lee, Yoon-Seon; Oh, Bum Jin; Lim, Kyoung Soo; Kim, Won Young

2017-02-21

To identify early predictive markers of poor outcomes in patients with acute liver injury from wild mushroom intoxication. This observational, retrospective record review involved adults aged ≥ 18 years admitted to emergency department with mushroom intoxication from January 2005 to December 2015. The diagnosis of mushroom intoxication was based on the following: (1) a positive history of recent wild mushroom intake (either raw or cooked); (2) the onset of gastrointestinal symptoms, such as watery diarrhea, vomiting, and/or abdominal pain, after ingestion; and (3) the exclusion of other possible causes of acute liver injury. Acute liver injury was defined by a > 5-fold elevation of liver enzymes or moderate coagulopathy [international normalized ratio (INR) > 2.0]. Clinical and laboratory findings were compared in survivors and non-survivors. Of 93 patients with mushroom intoxication, 23, 11 men (47.8%) and 12 women (52.2%), of median age 61 years, developed acute liver injury. The overall in-hospital mortality rate was 43.5% (10/23). Among the laboratory variables, mean serum alkaline phosphatase (73.38 ± 10.89 mg/dL vs 180.40 ± 65.39 mg/dL, P < 0.01), total bilirubin (2.312 ± 1.16 mg/dL vs 7.16 ± 2.94 mg/dL, P < 0.01) concentrations and indirect/direct bilirubin (2.45 ± 1.39 mg/dL vs 0.99 ± 0.45 mg/dL, P < 0.01) ratio as well as prothrombin time (1.88 ± 0.83 mg/dL vs 10.43 ± 4.81 mg/dL, P < 0.01), and activated partial thromboplastin time (aPTT; 32.48 ± 7.64 s vs 72.58 ± 41.29 s, P = 0.01), were significantly higher in non-survivors than in survivors. Logistic regression analysis showed that total bilirubin concentration (OR = 3.58, 95%CI: 1.25-10.22), indirect/direct bilirubin ratio (OR = 0.14, 95%CI: 0.02-0.94) and aPTT (OR = 1.30, 95%CI: 1.04-1.63) were significantly associated with mortality. All patients with total bilirubin > 5 mg/dL or aPTT > 50 s on day 3 died. Monitoring of bilirubin concentrations and aPTT may help in predicting clinical

Worsening Renal Function in Patients With Acute Heart Failure Undergoing Aggressive Diuresis Is Not Associated With Tubular Injury.