Singh, Sarvesh Pal
Acute kidney injury is a common complication after pediatric cardiac surgery. The definition, staging, risk factors, biomarkers and management of acute kidney injury in children is detailed in the following review article. PMID:27052074
Mao, Huijuan; Katz, Nevin; Ariyanon, Wassawon; Blanca-Martos, Lourdes; Adýbelli, Zelal; Giuliani, Anna; Danesi, Tommaso Hinna; Kim, Jeong Chul; Nayak, Akash; Neri, Mauro; Virzi, Grazia Maria; Brocca, Alessandra; Scalzotto, Elisa; Salvador, Loris; Ronco, Claudio
Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common and serious postoperative complication of cardiac surgery requiring cardiopulmonary bypass (CPB), and it is the second most common cause of AKI in the intensive care unit. Although the complication has been associated with the use of CPB, the etiology is likely multifactorial and related to intraoperative and early postoperative management including pharmacologic therapy. To date, very little evidence from randomized trials supporting specific interventions to protect from or prevent AKI in broad cardiac surgery populations has been found. The definition of AKI employed by investigators influences not only the incidence of CSA-AKI, but also the identification of risk variables. The advent of novel biomarkers of kidney injury has the potential to facilitate the subclinical diagnosis of CSA-AKI, the assessment of its severity and prognosis, and the early institution of interventions to prevent or reduce kidney damage. Further studies are needed to determine how to optimize cardiac surgical procedures, CPB parameters, and intraoperative and early postoperative blood pressure and renal blood flow to reduce the risk of CSA-AKI. No pharmacologic strategy has demonstrated clear efficacy in the prevention of CSA-AKI; however, some agents, such as the natriuretic peptide nesiritide and the dopamine agonist fenoldopam, have shown promising results in renoprotection. It remains unclear whether CSA-AKI patients can benefit from the early institution of such pharmacologic agents or the early initiation of renal replacement therapy. PMID:24454314
Kramer, Robert S.; Herron, Crystal R.; Groom, Robert C.; Brown, Jeremiah R.
Abstract: Acute kidney injury (AKI) after cardiac surgery is a common and underappreciated syndrome that is associated with poor short- and long-term outcomes. AKI after cardiac surgery may be epiphenomenon, a signal for adverse outcomes by virtue of other affected organ systems, and a consequence of multiple factors. Subtle increases in serum creatinine (SCr) postoperatively, once considered inconsequential, have been shown to reflect a kidney injury that likely occurred in the operating room during cardiopulmonary bypass (CPB) and more often in susceptible individuals. The postoperative elevation in SCr is a delayed signal reflecting the intraoperative injury. Preoperative checklists and the conduct of CPB represent opportunities for prevention of AKI. Newer definitions of AKI provide us with an opportunity to scrutinize perioperative processes of care and determine strategies to decrease the incidence of AKI subsequent to cardiac surgery. Recognizing and mitigating risk factors preoperatively and optimizing intraoperative practices may, in the aggregate, decrease the incidence of AKI. This review explores the pathophysiology of AKI and addresses the features of patients who are the most vulnerable to AKI. Preoperative strategies are discussed with particular attention to a readiness for surgery checklist. Intraoperative strategies include minimizing hemodilution and maximizing oxygen delivery with specific suggestions regarding fluid management and plasma preservation. PMID:26390675
Ortega-Loubon, Christian; Fernández-Molina, Manuel; Carrascal-Hinojal, Yolanda; Fulquet-Carreras, Enrique
Cardiac surgery-associated acute kidney injury (CSA-AKI) is a well-recognized complication resulting with the higher morbid-mortality after cardiac surgery. In its most severe form, it increases the odds ratio of operative mortality 3–8-fold, length of stay in the Intensive Care Unit and hospital, and costs of care. Early diagnosis is critical for an optimal treatment of this complication. Just as the identification and correction of preoperative risk factors, the use of prophylactic measures during and after surgery to optimize renal function is essential to improve postoperative morbidity and mortality of these patients. Cardiopulmonary bypass produces an increased in tubular damage markers. Their measurement may be the most sensitive means of early detection of AKI because serum creatinine changes occur 48 h to 7 days after the original insult. Tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 are most promising as an early diagnostic tool. However, the ideal noninvasive, specific, sensitive, reproducible biomarker for the detection of AKI within 24 h is still not found. This article provides a review of the different perspectives of the CSA-AKI, including pathogenesis, risk factors, diagnosis, biomarkers, classification, postoperative management, and treatment. We searched the electronic databases, MEDLINE, PubMed, EMBASE using search terms relevant including pathogenesis, risk factors, diagnosis, biomarkers, classification, postoperative management, and treatment, in order to provide an exhaustive review of the different perspectives of the CSA-AKI. PMID:27716701
Marcì, Marcello; Savatteri, Paolino; Pizzuto, Antonino; Giammona, Giuseppe; Renda, Baldassare; Lojacono, Francesca; Sanfilippo, Nicola
It is well known that cardiopulmonary complications are often associated to subarachnoid haemorrhage. For appropriate therapeutic managing it is very important to distinguish acute coronary syndrome from neurogenic myocardial injury, which is a reversible condition. Furthermore, because the hearts of brain dead patients may be utilized for therapeutic purpose, it has became of importance to rule out erroneous diagnosis of cardiac ischemia in order to avoid rejection of hearts potential suitable for transplantation.We present a report of two female patients affected by cardiac complications caused by aneurismal subarachnoid haemorrhage admitted to our neurosurgical intensive care department.
Palomba, H; de Castro, I; Neto, A L C; Lage, S; Yu, L
Acute kidney injury (AKI) following cardiac surgery (AKICS) is associated with increased postoperative (post-op) morbidity and mortality. A prognostic score system for AKI would help anticipate patient (pt) treatment. To develop a predictive score (AKICS) for AKI following cardiac surgery, we used a broad definition of AKI, which included perioperative variables. Six hundred three pts undergoing cardiac surgery were prospectively evaluated for AKI defined as serum creatinine above 2.0 mg/dl or an increase of 50% above baseline value. Univariate and multivariate analyses were used to evaluate pre-, intra-, and post-op parameters associated with AKI. The AKICS scoring system was prospectively validated in a new data set of 215 pts with an incidence of AKI of 14%. Variables included in the AKICS score were age greater than 65, pre-op creatinine above 1.2 mg/dl, pre-op capillary glucose above 140 mg/dl, heart failure, combined surgeries, cardiopulmonary bypass time above 2 h, low cardiac output, and low central venous pressure. The AKICS score presented good calibration and discrimination in both the study group and validation data set. The AKICS system that we developed, which incorporates five risk categories, accurately predicts AKI following cardiac surgery.
Coppolino, Giuseppe; Presta, Piera; Saturno, Laura; Fuiano, Giorgio
The incidence of postoperative acute kidney injury (AKI) in patients undergoing cardiac surgery ranges from 7.7% to 28.1% in different studies, probably in relation to the criteria adopted to define AKI. AKI markedly increases mortality risk. However, despite the development of less invasive techniques, cardiac surgery remains the first option in many conditions such as severe coronary artery disease, valve diseases and complex interventions. The risk of postsurgery AKI can be reduced by adopting less invasive approaches, such as off-pump coronary artery bypass grafting or transcatheter aortic valve implantation, but these options cannot be employed in all cases. Thus, since traditional cardiac surgery remains the only option in many cases, it is important to adopt strategies helping the clinician to prevent AKI or diagnose it early. Old age, preprocedural chronic kidney disease, obesity, some comorbidities, wide pulse pressure and some pharmacological regimens represent risk factors for postsurgery AKI and mortality. Important intraoperative factor are use and duration of cardiopulmonary bypass. Postoperative efforts should be aimed toward maximizing cardiac output, avoiding drugs vasoconstricting the renal artery, providing adequate crystalloid infusion and alkalinizing urine. Fluid management should not be based on the measurements for cardiac filling pressures, which are mostly unreliable in these patients. Novel biomarkers such as cystatin C, kidney injury molecule-1 and human neutrophil gelatinase-associated lipocalin have been found to change earlier than creatinine, particularly when measured in combination, so their use in clinical practice can facilitate early diagnosis and treatment of AKI. The occurrence of oliguria despite adequate cardiovascular therapy can be managed with furosemide, possibly using continuous infusion, or renal replacement therapy.
Jefferies, John Lynn; Devarajan, Prasad
Acute kidney injury (AKI) is increasingly recognized as a common problem in children undergoing cardiac surgery, with well documented increases in morbidity and mortality in both the short and the long term. Traditional approaches to the identification of AKI such as changes in serum creatinine have revealed a large incidence in this population with significant negative impact on clinical outcomes. However, the traditional diagnostic approaches to AKI diagnosis have inherent limitations that may lead to under-diagnosis of this pathologic process. There is a dearth of randomized controlled trials for the prevention and treatment of AKI associated with cardiac surgery, at least in part due to the paucity of early predictive biomarkers. Novel non-invasive biomarkers have ushered in a new era that allows for earlier detection of AKI. With these new diagnostic tools, a more consistent approach can be employed across centers that may facilitate a more accurate representation of the actual prevalence of AKI and more importantly, clinical investigation that may minimize the occurrence of AKI following pediatric cardiac surgery. A thoughtful management approach is necessary to mitigate the effects of AKI after cardiac surgery, which is best accomplished in close collaboration with pediatric nephrologists. Long-term surveillance for improvement in kidney function and potential development of chronic kidney disease should also be a part of the comprehensive management strategy. PMID:27429538
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
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.
Ishida, Kenichiro; Kinoshita, Yoshihiro; Iwasa, Nobutaka; Nakae, Masaro; Sakaki, Masayuki; Ieki, Yohei; Takahashi, Kyosuke; Shimahara, Yumiko; Sogabe, Taku; Shimono, Keiichiro; Noborio, Mitsuhiro; Sadamitsu, Daikai
Traumatic blunt cardiac injuries have a high mortality rate, and prompt diagnosis and treatment can be lifesaving in cardiac tamponade. A 62-year-old man was transferred to the emergency department after a motor vehicle accident. He was hemodynamically unstable. A focused assessment with sonography in trauma (FAST) showed pericardial fluid with right ventricular collapse consistent with cardiac tamponade in the subxiphoid view. He collapsed despite a subxiphoid pericardiotomy. Owing to the ongoing hemodynamic instability, we performed a left anterolateral thoracotomy. Direct incision of the pericardium showed blood and clots within the pericardial space, indicating hemopericardium. The heart stroke and hemodynamic status recovered on removing the clot. Although the physical findings of cardiac tamponade are not always apparent in life-threatening acute cardiac tamponade after blunt trauma, FAST is a reliable tool for diagnosing and following cardiac tamponade. A median sternotomy is a standard approach for evaluating cardiac injury in hemodynamically stable patients with or without cardiopulmonary bypass. However, a left anterior thoracotomy was the fastest, simplest life-saving procedure considering the need for open-chest cardiac massage given our patient's life-threatening condition. A prompt diagnosis using FAST and treatment can be lifesaving in traumatic acute cardiac tamponade. A pericardiotomy via a thoracotomy is mandatory for lifesaving cardiac decompression in acute traumatic cardiac tamponade in cases of ineffective drainage due to clot formation within the pericardial space. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Petek, Bradley J; Bravo, Paco E; Kim, Francis; de Boer, Ian H; Kudenchuk, Peter J; Shuman, William P; Gunn, Martin L; Carlbom, David J; Gill, Edward A; Maynard, Charles; Branch, Kelley R
Survivors of sudden cardiac arrest may be exposed to iodinated contrast from invasive coronary angiography or contrast-enhanced computed tomography, although the effects on incident acute kidney injury are unknown. The study objective was to determine whether contrast administration within the first 24 hours was associated with acute kidney injury in survivors of sudden cardiac arrest. This cohort study, derived from a prospective clinical trial, included patients with sudden cardiac arrest who survived for 48 hours, had no history of end-stage renal disease, and had at least 2 serum creatinine measurements during hospitalization. The contrast group included patients with exposure to iodinated contrast within 24 hours of sudden cardiac arrest. Incident acute kidney injury and first-time dialysis were compared between contrast and no contrast groups and then controlled for known acute kidney injury risk factors. Of the 199 survivors of sudden cardiac arrest, 94 received iodinated contrast. Mean baseline serum creatinine level was 1.3 mg/dL (95% confidence interval [CI] 1.4 to 1.5 mg/dL) for the contrast group and 1.6 mg/dL (95% CI 1.4 to 1.7 mg/dL) for the no contrast group. Incident acute kidney injury was lower in the contrast group (12.8%) than the no contrast group (17.1%; difference 4.4%; 95% CI -9.2% to 17.5%). Contrast administration was not associated with significant increases in incident acute kidney injury within quartiles of baseline serum creatinine level or after controlling for age, sex, race, congestive heart failure, diabetes, and admission serum creatinine level by regression analysis. Older age was independently associated with acute kidney injury. Despite elevated baseline serum creatinine level in most survivors of sudden cardiac arrest, iodinated contrast administration was not associated with incident acute kidney injury even when other acute kidney injury risk factors were controlled for. Thus, although acute kidney injury is not uncommon
Kališnik, Jurij Matija
Acute kidney injury after cardiac surgery with cardiopulmonary bypass is a common and serious complication and it is associated with increased morbidity and mortality. Diagnosis of acute kidney injury is based on the serum creatinine levels which rise several hours to days after the initial injury. Thus, novel biomarkers that will enable faster diagnosis are needed in clinical practice. There are numerous urine and serum proteins that indicate kidney injury and are under extensive research. Despite promising basic research results and assembled data, which indicate superiority of some biomarkers to creatinine, we are still awaiting clinical application. PMID:27212976
Santana-Santos, Eduesley; Marcusso, Marila Eduara Fátima; Rodrigues, Amanda Oliveira; de Queiroz, Fernanda Gomes; de Oliveira, Larissa Bertacchini; Rodrigues, Adriano Rogério Baldacin; Palomo, Jurema da Silva Herbas
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. PMID:25028954
Introduction The RIFLE (risk, injury, failure, loss of kidney function, and end-stage renal failure) classification for acute kidney injury (AKI) was recently modified by the Acute Kidney Injury Network (AKIN). The two definition systems differ in several aspects, and it is not clearly determined which has the better clinical accuracy. Methods In a retrospective observational study we investigated 4,836 consecutive patients undergoing cardiac surgery with cardiopulmonary bypass from 2005 to 2007 at Mayo Clinic, Rochester, MN, USA. AKI was defined by RIFLE and AKIN criteria. Results Significantly more patients were diagnosed as AKI by AKIN (26.3%) than by RIFLE (18.9%) criteria (P < 0.0001). Both definitions showed excellent association to outcome variables with worse outcome by increased severity of AKI (P < 0.001, all variables). Mortality was increased with an odds ratio (OR) of 4.5 (95% CI 3.6 to 5.6) for one class increase by RIFLE and an OR of 5.3 (95% CI 4.3 to 6.6) for one stage increase by AKIN. The multivariate model showed lower predictive ability of RIFLE for mortality. Patients classified as AKI in one but not in the other definition set were predominantly staged in the lowest AKI severity class (9.6% of patients in AKIN stage 1, 2.3% of patients in RIFLE class R). Potential misclassification of AKI is higher in AKIN, which is related to moving the 48-hour diagnostic window applied in AKIN criteria only. The greatest disagreement between both definition sets could be detected in patients with initial postoperative decrease of serum creatinine. Conclusions Modification of RIFLE by staging of all patients with acute renal replacement therapy (RRT) in the failure class F may improve predictive value. AKIN applied in patients undergoing cardiac surgery without correction of serum creatinine for fluid balance may lead to over-diagnosis of AKI (poor positive predictive value). Balancing limitations of both definition sets of AKI, we suggest application of the
Cardiac surgery-associated acute kidney injury (AKI) is common and is associated with a high mortality rate. Traditional biomarkers of AKI (creatinine and urea) increase slowly in response to renal injury, are insensitive to mild degrees of AKI, and are influenced by nonrenal factors. There is considerable interest in novel biomarkers of AKI such as neutrophil gelatinase-associated lipocalin that increase rapidly after renal injury, detect mild degrees of AKI, and are less subject to nonrenal factors. It has been postulated that the early diagnosis of cardiac surgery-associated AKI using novel biomarkers will result in improved outcomes. However, there is little evidence that interventions started early in the course of evolving AKI enhance renal recovery. Until effective therapies are developed that significantly improve the outcome from AKI, there is little benefit from early diagnosis using novel biomarkers.
Jung, Su-Young; Park, Jung Tak; Kwon, Young Eun; Kim, Hyung Woo; Ryu, Geun Woo; Lee, Sul A; Park, Seohyun; Jhee, Jong Hyun; Oh, Hyung Jung; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook
Acute kidney injury (AKI) after cardiac surgery is a common and serious complication. Although lower than normal serum bicarbonate levels are known to be associated with consecutive renal function deterioration in patients with chronic kidney injury, it is not well-known whether preoperative low serum bicarbonate levels are associated with the development of AKI in patients who undergo cardiac surgery. Therefore, the clinical implication of preoperative serum bicarbonate levels on AKI occurrence after cardiac surgery was investigated. Patients who underwent coronary artery bypass or valve surgery at Yonsei University Health System from January 2013 to December 2014 were enrolled. The patients were divided into 3 groups based on preoperative serum bicarbonate levels, which represented group 1 (below normal levels) <23 mEq/L; group 2 (normal levels) 23 to 24 mEq/L; and group 3 (elevated levels) >24 mEq/L. The primary outcome was the predicated incidence of AKI 48 hours after cardiac surgery. AKI was defined according to Acute Kidney Injury Network criteria. Among 875 patients, 228 (26.1%) developed AKI within 48 hours after cardiac surgery. The incidence of AKI was higher in group 1 (40.9%) than in group 2 (26.5%) and group 3 (19.5%) (P < 0.001). In addition, the duration of postoperative stay in a hospital intensive care unit (ICU) was longer for AKI patients and for those in the low-preoperative-serum-bicarbonate-level groups. A multivariate logistic regression analysis showed that low preoperative serum bicarbonate levels were significantly associated with AKI even after adjustment for age, sex, hypertension, diabetes mellitus, operation type, preoperative hemoglobin, and estimated glomerular filtration rate. In conclusion, low serum bicarbonate levels were associated with higher incidence of AKI and prolonged ICU stay. Further studies are needed to clarify whether strict correction of bicarbonate levels close to normal limits may have a protective
Murphy, Elizabeth; Steenbergen, Charles
Mitochondria play an important role in cell death and cardioprotection. During ischemia, when ATP is progressively deleted, ion pumps cannot function resulting in a rise in calcium (Ca2+), which further accelerates ATP depletion. The rise in Ca2+ during ischemia and reperfusion leads to mitochondrial Ca2+ accumulation, particularly during reperfusion when oxygen is reintroduced. Reintroduction of oxygen allows generation of ATP; however damage to electron transport chain results in increased mitochondrial generation of reactive oxygen species (ROS). Mitochondrial Ca2+ overload, and increased ROS can result in opening of the mitochondrial permeability transition pore, which further compromises cellular energetics. The resultant low ATP and altered ion homeostasis result in rupture of the plasma membrane and cell death. Mitochondria have long been proposed as central players in cell death, since the mitochondria are central to synthesis of both ATP and ROS and since mitochondrial and cytosolic Ca2+ overload are key components of cell death. Many cardioprotective mechanisms converge on the mitochondria to reduce cell death. Reducing Ca2+ overload and reducing ROS have both been reported to reduce ischemic injury. Preconditioning activates a number of signaling pathways that reduce Ca2+ overload and reduce activation of the mitochondrial permeability transition pore. The mitochondrial targets of cardioprotective signals will be discussed in detail. PMID:18391174
Jung, Su-Young; Park, Jung Tak; Kwon, Young Eun; Kim, Hyung Woo; Ryu, Geun Woo; Lee, Sul A.; Park, Seohyun; Jhee, Jong Hyun; Oh, Hyung Jung; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook
Abstract Acute kidney injury (AKI) after cardiac surgery is a common and serious complication. Although lower than normal serum bicarbonate levels are known to be associated with consecutive renal function deterioration in patients with chronic kidney injury, it is not well-known whether preoperative low serum bicarbonate levels are associated with the development of AKI in patients who undergo cardiac surgery. Therefore, the clinical implication of preoperative serum bicarbonate levels on AKI occurrence after cardiac surgery was investigated. Patients who underwent coronary artery bypass or valve surgery at Yonsei University Health System from January 2013 to December 2014 were enrolled. The patients were divided into 3 groups based on preoperative serum bicarbonate levels, which represented group 1 (below normal levels) <23 mEq/L; group 2 (normal levels) 23 to 24 mEq/L; and group 3 (elevated levels) >24 mEq/L. The primary outcome was the predicated incidence of AKI 48 hours after cardiac surgery. AKI was defined according to Acute Kidney Injury Network criteria. Among 875 patients, 228 (26.1%) developed AKI within 48 hours after cardiac surgery. The incidence of AKI was higher in group 1 (40.9%) than in group 2 (26.5%) and group 3 (19.5%) (P < 0.001). In addition, the duration of postoperative stay in a hospital intensive care unit (ICU) was longer for AKI patients and for those in the low-preoperative-serum-bicarbonate-level groups. A multivariate logistic regression analysis showed that low preoperative serum bicarbonate levels were significantly associated with AKI even after adjustment for age, sex, hypertension, diabetes mellitus, operation type, preoperative hemoglobin, and estimated glomerular filtration rate. In conclusion, low serum bicarbonate levels were associated with higher incidence of AKI and prolonged ICU stay. Further studies are needed to clarify whether strict correction of bicarbonate levels close to normal limits may have a
Li, T-T; Jia, L-X; Zhang, W-M; Li, X-Y; Zhang, J; Li, Y-L; Li, H-H; Qi, Y-F; Du, J
Inflammation plays an important role in hypertensive cardiac injury. The endoplasmic reticulum (ER) stress pathway is involved in the inflammatory response. However, the role of ER stress in elevated angiotensin II (Ang II)-induced cardiac injury remains unclear. In this study, we investigated the role of ER stress in Ang II-induced hypertensive cardiac injury. Transcriptome analysis and quantitative real-time PCR showed that Ang II infusion in mice increased ER stress-related genes expression in the heart. C/EBP homologous protein (CHOP) deficiency, a key mediator of ER stress, increased infiltration of inflammatory cells, especially neutrophils, the production of inflammatory cytokines, chemokines in Ang II-infused mouse hearts. CHOP deficiency increased Ang II-induced cardiac fibrotic injury: (1) Masson trichrome staining showed increased fibrotic areas, (2) immunohistochemistry staining showed increased expression of α-smooth muscle actin, transforming growth factor β1 and (3) quantitative real-time PCR showed increased expression of collagen in CHOP-deficient mouse heart. Bone marrow transplantation experiments indicated that CHOP deficiency in bone marrow cells was responsible for Ang II-induced cardiac fibrotic injury. Moreover, TUNEL staining and flow cytometry revealed that CHOP deficiency decreased neutrophil apoptosis in response to Ang II. Taken together, our study demonstrated that hypertension induced ER stress after Ang II infusion. ER stress in bone marrow-derived cells protected acute cardiac inflammation and injury in response to Ang II.
Brown, Jeremiah R.; Kramer, Robert S.; MacKenzie, Todd A.; Coca, Steven G.; Sint, Kyaw; Parikh, Chirag R.
Background Acute kidney injury (AKI) duration following cardiac surgery is associated with poor survival in a dose-dependent manner. However, it is not known what peri-operative risk factors contribute to prolonged AKI and delayed recovery. We sought to identify peri-operative risk factors that predict duration of AKI, a complication that effects short and long term survival. Methods We studied 4,987 consecutive cardiac surgery patients from 2002 through 2007. AKI was defined as a ≥0.3 (mg/dL) or ≥50% increase in SCr from baseline. Duration of AKI was defined by the number of days AKI was present. Step-wise multivariable negative binomial regression analysis was conducted using peri-operative risk factors for AKI duration. C-index was estimated by Kendall’s tau. Results AKI developed in 39% of patients with a median duration of AKI at 3 days and ranged from 1 to 108 days. Patients without AKI had duration of zero days. Independent predictors of AKI duration included baseline patient and disease characteristics, operative and post-operative factors. Prediction for mean duration of AKI was developed using coefficients from the regression model and externally validated the model on 1,219 cardiac surgery patients in a separate cardiac surgery cohort (TRIBE-AKI). The C-index was 0.65 (p<0.001) for the derivation cohort and 0.62 (p<0.001) for the validation cohort. Conclusion We identified and externally validated peri-operative predictors of AKI duration. These risk-factors will be useful to evaluate a patient’s risk for the tempo of recovery from AKI after cardiac surgery and subsequent short and long term survival. The level of awareness created by working with these risk factors have implications regarding positive changes in processes of care that have the potential to decrease the incidence and mitigate AKI. PMID:22206952
Choi, Dae-Kee; Kim, Wook-Jong; Chin, Ji-Hyun; Lee, Eun-Ho; Don Hahm, Kyung; Yeon Sim, Ji; Cheol Choi, In
To evaluate the usefulness of renal regional oxygen saturation (renal rSO2) in predicting the risk of acute kidney injury (AKI) after cardiac surgery. A prospective observational study. Tertiary care university hospital. One hundred patients undergoing cardiac surgery. Renal rSO2 was monitored continuously by near-infrared spectroscopy (NIRS) throughout the anesthetic period. Postoperative AKI was defined using the Risk, Injury, Failure, Loss, and End-stage (RIFLE) criteria. Of 95 patients who were included in the final analysis, 34 patients developed AKI after surgery. Recorded renal rSO2 data were used to calculate the total duration of the time when renal rSO2 was below the threshold values of 70%, 65%, 60%, 55%, and 50%. The total periods when the renal rSO2 level was below each of the threshold values were significantly longer in patients with AKI than in those without AKI (p = 0.001 or p<0.001). Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive power of renal rSO2 for AKI. The ROC curve analysis showed that renal rSO2 could predict the risk of AKI with statistical significance and that a renal rSO2<55% had the best performance (area under the curve-ROC, 0.777; 95% CI, 0.669-0.885; p<0.001). Multivariate logistic regression analysis revealed that AKI significantly correlated with the duration of renal rSO2<55% (p = 0.002) and logistic EuroSCORE (p = 0.007). Intraoperative renal regional oxygen desaturation can be a good predictor of AKI in adult patients undergoing cardiac surgery. Copyright © 2014 Elsevier Inc. All rights reserved.
Chen, Lijuan; Wang, Yingjie; Pan, Yaohua; Zhang, Lan; Shen, Chengxing; Qin, Gangjian; Ashraf, Muhammad; Weintraub, Neal; Ma, Genshan; Tang, Yaoliang
Highlights: ► Cardiac progenitor-derived (CPC) Exosomes protect H9C2 from apoptosis in vitro. ► CPC-exosomes protect cardiomyoyctes from MI/R induced apoptosis in vivo. ► CPC-exosomes were taken up by H9C2 with high efficiency using PKH26 labeling. ► miR-451, one of GATA4-responsive miRNA cluster, is enriched in CPC-exosomes. -- Abstract: Background: Cardiac progenitors (CPC) mediate cardioprotection via paracrine effects. To date, most of studies focused on secreted paracrine proteins. Here we investigated the CPC-derived-exosomes on protecting myocardium from acute ischemia/reperfusion (MI/R) injury. Methods and results: CPC were isolated from mouse heart using two-step protocol. Exosomes were purified from conditional medium, and confirmed by electron micrograph and Western blot using CD63 as a marker. qRT-PCR shows that CPC-exosomes have high level expression of GATA4-responsive-miR-451. Exosomes were ex vivo labeled with PKH26, We observed exosomes can be uptaken by H9C2 cardiomyoblasts with high efficiency after 12 h incubation. CPC-exosomes protect H9C2 from oxidative stress by inhibiting caspase 3/7 activation invitro. In vivo delivery of CPC-exosomes in an acute mouse myocardial ischemia/reperfusion model inhibited cardiomyocyte apoptosis by about 53% in comparison with PBS control (p < 0.05). Conclusion: Our results suggest, for the first time, the CPC-exosomes can be used as a therapeutic vehicle for cardioprotection, and highlights a new perspective for using non-cell exosomes for cardiac disease.
Perez-Valdivieso, Jose Ramon; Monedero, Pablo; Vives, Marc; Garcia-Fernandez, Nuria; Bes-Rastrollo, Maira
Acute kidney injury is among the most serious complications after cardiac surgery and is associated with an impaired outcome. Multiple factors may concur in the development of this disease. Moreover, severe renal failure requiring renal replacement therapy (RRT) presents a high mortality rate. Consequently, we studied a Spanish cohort of patients to assess the risk factors for RRT in cardiac surgery-associated acute kidney injury (CSA-AKI). A retrospective case-cohort study in 24 Spanish hospitals. All cases of RRT after cardiac surgery in 2007 were matched in a crude ratio of 1:4 consecutive patients based on age, sex, treated in the same year, at the same hospital and by the same group of surgeons. We analyzed the data from 864 patients enrolled in 2007. In multivariate analysis, severe acute kidney injury requiring postoperative RRT was significantly associated with the following variables: lower glomerular filtration rates, less basal haemoglobin, lower left ventricular ejection fraction, diabetes, prior diuretic treatment, urgent surgery, longer aortic cross clamp times, intraoperative administration of aprotinin, and increased number of packed red blood cells (PRBC) transfused. When we conducted a propensity analysis using best-matched of 137 available pairs of patients, prior diuretic treatment, longer aortic cross clamp times and number of PRBC transfused were significantly associated with CSA-AKI.Patients requiring RRT needed longer hospital stays, and suffered higher mortality rates. Cardiac-surgery associated acute kidney injury requiring RRT is associated with worse outcomes. For this reason, modifiable risk factors should be optimised and higher risk patients for acute kidney injury should be identified before undertaking cardiac surgery.
Background Acute kidney injury is among the most serious complications after cardiac surgery and is associated with an impaired outcome. Multiple factors may concur in the development of this disease. Moreover, severe renal failure requiring renal replacement therapy (RRT) presents a high mortality rate. Consequently, we studied a Spanish cohort of patients to assess the risk factors for RRT in cardiac surgery-associated acute kidney injury (CSA-AKI). Methods A retrospective case-cohort study in 24 Spanish hospitals. All cases of RRT after cardiac surgery in 2007 were matched in a crude ratio of 1:4 consecutive patients based on age, sex, treated in the same year, at the same hospital and by the same group of surgeons. Results We analyzed the data from 864 patients enrolled in 2007. In multivariate analysis, severe acute kidney injury requiring postoperative RRT was significantly associated with the following variables: lower glomerular filtration rates, less basal haemoglobin, lower left ventricular ejection fraction, diabetes, prior diuretic treatment, urgent surgery, longer aortic cross clamp times, intraoperative administration of aprotinin, and increased number of packed red blood cells (PRBC) transfused. When we conducted a propensity analysis using best-matched of 137 available pairs of patients, prior diuretic treatment, longer aortic cross clamp times and number of PRBC transfused were significantly associated with CSA-AKI. Patients requiring RRT needed longer hospital stays, and suffered higher mortality rates. Conclusion Cardiac-surgery associated acute kidney injury requiring RRT is associated with worse outcomes. For this reason, modifiable risk factors should be optimised and higher risk patients for acute kidney injury should be identified before undertaking cardiac surgery. PMID:19772621
Young, Allen; Crawford, Todd; Pierre, Alejandro Suarez; Trent Magruder, J; Fraser, Charles; Conte, John; Whitman, Glenn; Sciortino, Christopher
Renal ultrasonography is part of the algorithm in assessing acute kidney injury (AKI). The purpose of this study was to assess the clinical utility of renal US in postoperative cardiac patients who develop AKI. We conducted a retrospective study of 90 postoperative cardiac surgery patients at a single institution from 1/19/2010 to 3/19/2016 who underwent renal US for AKI. We reviewed provider documentation to determine whether renal US changed management. We defined change as: administration of crystalloid or colloid, addition of inotropic or vasopressor, or procedural interventions on the renal system. Mean age of study patients was 68 ± 13 years. 48/90 patients (53.3%) had pre-existing chronic kidney disease of varying severity. 48 patients (53.3%) had normal renal US with incidental findings and 31 patients (34.4%) had US evidence of medical kidney disease. 10 patients (11.1%) had limited US results due to poor visualization and 1 patient (1.1%) had mild right-sided hydronephrosis. No patients were found to have obstructive uropathy or renal artery stenosis. Clinical management was altered in only 4/90 patients (4.4%), which included 3 patients that received a fluid bolus and 1 patient that received a fluid bolus and inotropes. No vascular or urologic procedures resulted from US findings. Although renal ultrasound is often utilized in the work-up of AKI, our study shows that renal US provides little benefit in managing postoperative cardiac patients. This diagnostic modality should be scrutinized rather than viewed as a universal measure in the cardiac surgery population.
Introduction Fluid resuscitation in the critically ill often results in a positive fluid balance, potentially diluting the serum creatinine concentration and delaying diagnosis of acute kidney injury (AKI). Methods Dilution during AKI was quantified by combining creatinine and volume kinetics to account for fluid type, and rates of fluid infusion and urine output. The model was refined using simulated patients receiving crystalloids or colloids under four glomerular filtration rate (GFR) change scenarios and then applied to a cohort of critically ill patients following cardiac arrest. Results The creatinine concentration decreased during six hours of fluid infusion at 1 litre-per-hour in simulated patients, irrespective of fluid type or extent of change in GFR (from 0% to 67% reduction). This delayed diagnosis of AKI by 2 to 9 hours. Crystalloids reduced creatinine concentration by 11 to 19% whereas colloids reduced concentration by 36 to 43%. The greatest reduction was at the end of the infusion period. Fluid dilution alone could not explain the rapid reduction of plasma creatinine concentration observed in 39 of 49 patients after cardiac arrest. Additional loss of creatinine production could account for those changes. AKI was suggested in six patients demonstrating little change in creatinine, since a 52 ± 13% reduction in GFR was required after accounting for fluid dilution and reduced creatinine production. Increased injury biomarkers within a few hours of cardiac arrest, including urinary cystatin C and plasma and urinary Neutrophil-Gelatinase-Associated-Lipocalin (biomarker-positive, creatinine-negative patients) also indicated AKI in these patients. Conclusions Creatinine and volume kinetics combined to quantify GFR loss, even in the absence of an increase in creatinine. The model improved disease severity estimation, and demonstrated that diagnostic delays due to dilution are minimally affected by fluid type. Creatinine sampling should be delayed at least
Burke-Gaffney, Anne; Svermova, Tatiana; Mumby, Sharon; Finney, Simon J.; Evans, Timothy W.
Objective Endothelial dysfunction associated with systemic inflammation can contribute to organ injury/failure following cardiac surgery requiring cardiopulmonary bypass (CPB). Roundabout protein 4 (Robo4), an endothelial-expressed transmembrane receptor and regulator of cell activation, is an important inhibitor of endothelial hyper-permeability. We investigated the hypothesis that plasma levels of Robo4 are indicative of organ injury, in particular acute kidney injury (AKI), after cardiac surgery. Methods Patients (n = 32) undergoing elective cardiac surgery with CPB were enrolled, prospectively. Plasma Robo4 concentrations were measured pre-, 2 and 24 h post-operatively, using a commercially available ELISA. Plasma and endothelial markers of inflammation [interleukin (IL) -6, -8, -10: von Willibrand factor (vWF) and angiopoeitin-2 (Ang-2)] and the AKI marker, neutrophil gelatinase-associated lipocalin (NGAL), were also measured by ELISA. Results Plasma Robo4 increased significantly (p<0.001) from pre-operative levels of 2515±904 pg/ml to 4473±1915 pg/ml, 2 h after surgery; and returned to basal levels (2682±979 pg/ml) by 24 h. Plasma cytokines, vWF and NGAL also increased 2 h post-operatively and remained elevated at 24 h. Ang-2 increased 24 h post-operatively, only. There was a positive, significant correlation (r = 0.385, p = 0.0298) between Robo-4 and IL-10, but not other cytokines, 2 h post-operatively. Whilst raised Robo4 did not correlate with indices of lung dysfunction or other biomarkers of endothelial activation; there was a positive, significant correlation between raised (2 h) plasma NGAL and Robo4 (r = 0.4322, p = 0.0135). When patients were classed as AKI or non-AKI either using NGAL cut-off of 150 ng/ml, or the AKI Network (AKIN) clinical classification; plasma Robo4 was significantly higher (p = 0.0073 and 0.003, respectively) in AKI vs. non-AKI patients (NGAL cut-off: 5350±2191 ng/ml, n = 16 vs. 3595±1068 pg
Gambardella, Ivancarmine; Gaudino, Mario; Ronco, Claudio; Lau, Christopher; Ivascu, Natalia; Girardi, Leonard N
Acute kidney injury (AKI) in cardiac surgery has traditionally been linked to reduced arterial perfusion. There is ongoing evidence that central venous pressure (CVP) has a pivotal role in precipitating acute renal dysfunction in cardiac medical and surgical settings. We can regard this AKI driven by systemic venous hypertension as 'kidney congestive failure'. In the cardiac surgery population as a whole, when the CVP value reaches the threshold of 14 mmHg in postoperative period, the risk of AKI increases 2-fold with an odds ratio (OR) of 1.99, 95% confidence interval (95% CI) of 1.16-3.40. In cardiac surgery subsets where venous hypertension is a hallmark feature, the incidence of AKI is higher (tricuspid disease 30%, carcinoid valve disease 22%). Even in the non-chronically congested coronary artery bypass population, CVP measured 6 h postoperatively showed significant association to renal failure: risk-adjusted OR for AKI was 5.5 (95% CI 1.93-15.5; P = 0.001) with every 5 mmHg rise in CVP for patients with CVP <9 mmHg; for CVP increments of 5 mmHg above the threshold of 9 mmHg, the risk-adjusted OR for AKI was 1.3 (95% CI 1.01-1.65; P = 0.045). This and other clinical evidence are discussed along with the underlying pathophysiological mechanisms, involving the supremacy of volume receptors in regulating the autonomic output in hypervolaemia, and the regional effect of venous congestion on the nephron. The effect of CVP on renal function was found to be modulated by ventricular function class, aetiology and acuity of venous congestion. Evidence suggests that acute increases of CVP should be actively treated to avoid a deterioration of the renal function, particularly in patients with poor ventricular fraction. Besides, the practice of treating right heart failure with fluid loading should be avoided in favour of other ways to optimize haemodynamics in this setting, because of the detrimental effects on the kidney function.
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
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
de Moura, Edmilson Bastos; Bernardes Neto, Saint-Clair Gomes; Amorim, Fábio Ferreira; Viscardi, Renato Camargo
Objective The objective of this study was to assess the correlation between the European System for Cardiac Operative Risk Evaluation (EuroSCORE) score and the risk of developing acute kidney injury in cardiac surgery patients. Methods This retrospective study was conducted at a tertiary hospital on consecutive cardiac surgery patients (e.g., valvular, ischemic and congenital heart diseases) between October 2010 and July 2011. Results One hundred patients were assessed. Among the 100 patients, six were excluded, including five because of prior kidney disease or dialysis therapy and one because of incomplete medical records. The primary surgical indications were myocardial revascularization in 55 patients (58.5% of cases) and valve replacement in 28 patients (29.8%). According to the EuroSCORE, 55 patients were classified as high risk (58.5%), 27 patients as medium risk (28.7%) and 12 patients as low risk (12.8%). In the postoperative period, patients were classified with the Risk, Injury, Failure, Loss and End-stage kidney disease (RIFLE) score. Among the 31 patients (33%) who displayed an increase in serum creatinine, 18 patients (19.1%) were classified as RIFLE "R" (risk), seven patients (7.4%) were classified as RIFLE "I" (injury) and six patients (6.5%) were classified as RIFLE "F" (failure). Among the patients who were considered to be high risk according to the EuroSCORE criteria, 24 patients (43.6%) showed acute kidney injury. Among the patients who were classified as medium or low risk, acute kidney injury occurred in 18.5 and 16.6% of the cases, respectively. The correlations between risk stratification (low, medium and high) and the EuroSCORE and postoperative RIFLE scores were statistically significant (p=0.03). Conclusion In the studied population, there was a statistically significant correlation between the EuroSCORE and the risk of developing acute kidney injury in the postoperative period after cardiac surgery. PMID:24213087
Moledina, Dennis G; Isguven, Selin; McArthur, Eric; Thiessen-Philbrook, Heather; Garg, Amit X; Shlipak, Michael; Whitlock, Richard; Kavsak, Peter A; Coca, Steven G; Parikh, Chirag R
Monocyte chemotactic protein-1 (MCP-1; chemokine C-C ligand-2 [CCL-2]) is upregulated in ischemia-reperfusion injury and is a promising biomarker of inflammation in cardiac operations. We measured preoperative and postoperative plasma MCP-1 levels in adults undergoing cardiac operations to evaluate the association of perioperative MCP-1 levels with acute kidney injury (AKI) and death in Translational Research Investigating Biomarker Endpoints in AKI (TRIBE-AKI), a prospective, multicenter, observational cohort. Of the 972 participants in the study, AKI developed in 329 (34%), and severe AKI developed in 45 (5%). During a median follow-up of 2.9 years (interquartile range, 2.2 to 3.5 years), 119 participants (12%) died. MCP-1 levels were significantly higher in those who developed AKI and died than in those without AKI and death. Participants with a preoperative MCP-1 level in the highest tertile (>196 pg/mL) had an increased AKI risk than those in the lowest tertile (<147 pg/mL; odds ratio [OR], 1.43l; 95% confidence interval [CI], 1.00 to 2.05). The association appeared similar but was not significant for the severe AKI outcome (OR, 1.48; 95% CI, 0.62 to 3.54). Compared with participants with preoperative MCP-1 level in the lowest tertile, those in the highest tertile had higher adjusted risk of death (hazard ratio, 1.82; 95% CI, 1.40 to 2.38). Similarly, participants in the highest tertile had a higher adjusted risk of death (hazard ratio, 1.95; 95% CI, 1.09-3.49) than those with a postoperative MCP-1 level in the lowest tertile. Higher plasma MCP-1 is associated with increased AKI and risk of death after cardiac operations. MCP-1 could be used as a biomarker to identify high-risk patients for potential AKI prevention strategies in the setting of cardiac operations. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Cardoso, Bárbara; Laranjo, Sérgio; Gomes, Inês; Freitas, Isabel; Trigo, Conceição; Fragata, Isabel; Fragata, José; Pinto, Fátima
To characterize the epidemiology and risk factors for acute kidney injury (AKI) after pediatric cardiac surgery in our center, to determine its association with poor short-term outcomes, and to develop a logistic regression model that will predict the risk of AKI for the study population. This single-center, retrospective study included consecutive pediatric patients with congenital heart disease who underwent cardiac surgery between January 2010 and December 2012. Exclusion criteria were a history of renal disease, dialysis or renal transplantation. Of the 325 patients included, median age three years (1 day-18 years), AKI occurred in 40 (12.3%) on the first postoperative day. Overall mortality was 13 (4%), nine of whom were in the AKI group. AKI was significantly associated with length of intensive care unit stay, length of mechanical ventilation and in-hospital death (p<0.01). Patients' age and postoperative serum creatinine, blood urea nitrogen and lactate levels were included in the logistic regression model as predictor variables. The model accurately predicted AKI in this population, with a maximum combined sensitivity of 82.1% and specificity of 75.4%. AKI is common and is associated with poor short-term outcomes in this setting. Younger age and higher postoperative serum creatinine, blood urea nitrogen and lactate levels were powerful predictors of renal injury in this population. The proposed model could be a useful tool for risk stratification of these patients. Copyright © 2015 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.
Petrovic, Stanislava; Bogavac-Stanojevic, Natasa; Lakic, Dragana; Peco-Antic, Amira; Vulicevic, Irena; Ivanisevic, Ivana; Kotur-Stevuljevic, Jelena; Jelic-Ivanovic, Zorana
Acute kidney injury (AKI) is significant problem in children with congenital heart disease (CHD) who undergo cardiac surgery. The economic impact of a biomarker-based diagnostic strategy for AKI in pediatric populations undergoing CHD surgery is unknown. The aim of this study was to perform the cost effectiveness analysis of using serum cystatin C (sCysC), urine neutrophil gelatinase-associated lipocalin (uNGAL) and urine liver fatty acid-binding protein (uL-FABP) for the diagnosis of AKI in children after cardiac surgery compared with current diagnostic method (monitoring of serum creatinine (sCr) level). We developed a decision analytical model to estimate incremental cost-effectiveness of different biomarker-based diagnostic strategies compared to current diagnostic strategy. The Markov model was created to compare the lifetime cost associated with using of sCysC, uNGAL, uL-FABP with monitoring of sCr level for the diagnosis of AKI. The utility measurement included in the analysis was quality-adjusted life years (QALY). The results of the analysis are presented as the incremental cost-effectiveness ratio (ICER). Analysed biomarker-based diagnostic strategies for AKI were cost-effective compared to current diagnostic method. However, uNGAL and sCys C strategies yielded higher costs and lower effectiveness compared to uL-FABP strategy. uL-FABP added 1.43 QALY compared to current diagnostic method at an additional cost of $8521.87 per patient. Therefore, ICER for uL-FABP compared to sCr was $5959.35/QALY. Our results suggest that the use of uL-FABP would represent cost effective strategy for early diagnosis of AKI in children after cardiac surgery.
Coca, Steven G.; Thiessen-Philbrook, Heather; Shlipak, Michael G.; Koyner, Jay L.; Wang, Zhu; Edelstein, Charles L.; Devarajan, Prasad; Patel, Uptal D.; Zappitelli, Michael; Krawczeski, Catherine D.; Passik, Cary S.; Swaminathan, Madhav; Garg, Amit X.
Acute kidney injury (AKI) is a frequent complication of cardiac surgery and increases morbidity and mortality. The identification of reliable biomarkers that allow earlier diagnosis of AKI in the postoperative period may increase the success of therapeutic interventions. Here, we conducted a prospective, multicenter cohort study involving 1219 adults undergoing cardiac surgery to evaluate whether early postoperative measures of urine IL-18, urine neutrophil gelatinase-associated lipocalin (NGAL), or plasma NGAL could identify which patients would develop AKI and other adverse patient outcomes. Urine IL-18 and urine and plasma NGAL levels peaked within 6 hours after surgery. After multivariable adjustment, the highest quintiles of urine IL-18 and plasma NGAL associated with 6.8-fold and 5-fold higher odds of AKI, respectively, compared with the lowest quintiles. Elevated urine IL-18 and urine and plasma NGAL levels associated with longer length of hospital stay, longer intensive care unit stay, and higher risk for dialysis or death. The clinical prediction model for AKI had an area under the receiver-operating characteristic curve (AUC) of 0.69. Urine IL-18 and plasma NGAL significantly improved the AUC to 0.76 and 0.75, respectively. Urine IL-18 and plasma NGAL significantly improved risk prediction over the clinical models alone as measured by net reclassification improvement (NRI) and integrated discrimination improvement (IDI). In conclusion, urine IL-18, urine NGAL, and plasma NGAL associate with subsequent AKI and poor outcomes among adults undergoing cardiac surgery. (Clinical Trials.gov number, NCT00774137). PMID:21836143
Shi, Qiankun; Hong, Liang; Mu, Xinwei; Zhang, Cui; Chen, Xin
Abstract This study aimed to investigate the outcomes of acute kidney injury (AKI) after cardiac surgery by the meta-analysis. Electronic databases PubMed and Embase were searched for relative studies from December 2008 to June 2015. For eligible studies, the R software was conducted to meta-analyze outcomes of AKI patients (AKI group) and none-AKI patients after cardiac surgery (NO AKI group). The chi-square-based Q test and I2 statistic were used for heterogeneity analysis. P < 0.1 or I2 > 50% revealed significant heterogeneity among studies, and then a random effects model was used; otherwise a fixed effect model was performed. Egger's test was performed for publication bias assessment. Subgroup analysis was performed by stratifying AKI definitions and study type. Totally 17 studies with 9656 subjects (2331 in the AKI group and 7325 in the NO AKI group) were enrolled. Significantly higher renal replacement therapy (RRT) (OR=23.67, 95%CI: 12.58–44.55), mortality (OR = 6.27, 95%CI: 3.58–11.00), serum creatinine (SMD = 1.42, 95%CI: 1.01–1.83), and hospital length of stay (LOS) (SMD = 0.45, 95%CI: 0.02–0.88) were shown in the AKI group compared with patients in the NO AKI group. Subgroup analysis showed that results of only 3 subgroups were reversed indicating that the definition of AKI did not affect its outcomes. Publication bias was only found among studies involving mortality and serum creatinine, but the 2 outcomes were not reversed after correction. This meta-analysis confirmed the worse outcomes of AKI in patients after cardiac surgery, including higher RRT rates, mortality, and longer hospital LOS than those of NO AKI patients. PMID:27930561
Devarajan, Prasad; Zappitelli, Michael; Sint, Kyaw; Thiessen-Philbrook, Heather; Li, Simon; Kim, Richard W.; Koyner, Jay L.; Coca, Steven G.; Edelstein, Charles L.; Shlipak, Michael G.; Garg, Amit X.; Krawczeski, Catherine D.
Acute kidney injury (AKI) occurs commonly after pediatric cardiac surgery and associates with poor outcomes. Biomarkers may help the prediction or early identification of AKI, potentially increasing opportunities for therapeutic interventions. Here, we conducted a prospective, multicenter cohort study involving 311 children undergoing surgery for congenital cardiac lesions to evaluate whether early postoperative measures of urine IL-18, urine neutrophil gelatinase-associated lipocalin (NGAL), or plasma NGAL could identify which patients would develop AKI and other adverse outcomes. Urine IL-18 and urine and plasma NGAL levels peaked within 6 hours after surgery. Severe AKI, defined by dialysis or doubling in serum creatinine during hospital stay, occurred in 53 participants at a median of 2 days after surgery. The first postoperative urine IL-18 and urine NGAL levels strongly associated with severe AKI. After multivariable adjustment, the highest quintiles of urine IL-18 and urine NGAL associated with 6.9- and 4.1-fold higher odds of AKI, respectively, compared with the lowest quintiles. Elevated urine IL-18 and urine NGAL levels associated with longer hospital stay, longer intensive care unit stay, and duration of mechanical ventilation. The accuracy of urine IL-18 and urine NGAL for diagnosis of severe AKI was moderate, with areas under the curve of 0.72 and 0.71, respectively. The addition of these urine biomarkers improved risk prediction over clinical models alone as measured by net reclassification improvement and integrated discrimination improvement. In conclusion, urine IL-18 and urine NGAL, but not plasma NGAL, associate with subsequent AKI and poor outcomes among children undergoing cardiac surgery. PMID:21836147
Brown, Jeremiah R.; Kramer, Robert S.; Coca, Steven G.; Parikh, Chirag R.
Background Acute kidney injury (AKI) following cardiac surgery is associated with worse outcomes. However, it is not known how adverse long-term consequences vary according to the duration of AKI. We sought to determine the association between duration of AKI and survival. Methods 4,987 cardiac surgery patients from 2002 through 2007 with serum creatinine (SCr) collection at a medical center in northern New England. AKI was defined as a ≥0.3 (mg/dL) or ≥50% increase in SCr from baseline and further classified into AKI network stages. Duration of AKI was defined by the number of days AKI was present and categorized by: no AKI, AKI for 1–2, 3–6 and ≥7 days. Results 39% of patients developed AKI. Long-term survival was significantly different by AKI duration (p < 0.001). The proportion of patients with AKI duration, adjusted hazard ratios (HR) and 95% confidence intervals for mortality (no AKI as referent), were: 1–2 days (18%, HR 1.66; 1.32–2.09), 3–6 days (11%, HR 1.94; 1.51–2.49), ≥7 days (9%, HR 3.40; 2.73–4.25). This graded relationship of duration of AKI with long-term mortality persisted when patients who died during hospitalization were excluded from analysis (p < 0.001). Propensity matched analysis confirmed results. Conclusion The duration of AKI after cardiac surgery is directly proportional to long-term mortality. This AKI dose-dependent effect on long-term mortality helps to close the gap between association and causation, whereby AKI stages and AKI duration have important implications for patient care and can aid clinicians in evaluating the risk of in-hospital and post discharge death. PMID:20868804
Westphal, Martin; Morita, Naoki; Enkhbaatar, Perenlei; Murakami, Kazunori; Traber, Lillian; Traber, Daniel Lee
The objective of this study was to determine the relationship between carboxyhemoglobin (COHb) formation, global oxygen transport, and cardiac performance in the acute phase of combined burn and smoke inhalation injury. Following a third degree burn of 20% of the total body surface area, adult sheep were subjected to cotton smoke (4x12 breaths) according to an established protocol. Compared with baseline (BL), the burn injury led to an immediate and sustained COHb-independent depression in myocardial contractility. Despite a progressive increase in COHb formation, up to a maximum of 78+/-3% (P < 0.001 vs BL), smoke inhalation did not further impair these hemodynamic changes. This study demonstrated that in the early stage of combined burn and smoke inhalation injury, the depression in cardiac function is basically triggered by the burn injury, whereas COHb generation secondary to cotton smoke exposure primarily contributes to pulmonary shunting.
Schaub, Jennifer A.; Garg, Amit X.; Coca, Steven G.; Testani, Jeffrey M.; Shlipak, Michael G.; Eikelboom, John; Kavsak, Peter; McArthur, Eric; Shortt, Colleen; Whitlock, Richard; Parikh, Chirag R.
Acute Kidney Injury (AKI) is a common complication after cardiac surgery and is associated with worse outcomes. Since heart fatty acid binding protein (H-FABP) is a myocardial protein that detects cardiac injury, we sought to determine if plasma H-FABP was associated with AKI in the TRIBE-AKI cohort; a multi-center cohort of 1219 patients at high risk for AKI who underwent cardiac surgery. The primary outcomes of interest were any AKI (Acute Kidney Injury Network (AKIN) stage 1 or higher) and severe AKI (AKIN stage 2 or higher). The secondary outcome was long-term mortality after discharge. Patients who developed AKI had higher levels of H-FABP pre- and post-operatively than patients who did not have AKI. In analyses adjusted for known AKI risk factors, first post-operative log(H-FABP) was associated with severe AKI (adjusted OR 5.39 [95% CI, 2.87-10.11] per unit increase), while pre-operative log(H-FABP) was associated with any AKI (2.07 [1.48-2.89]) and mortality (1.67 [1.17-2.37]). These relationships persisted after adjustment for change in serum creatinine (for first postoperative log(H-FABP)) and biomarkers of cardiac and kidney injury, including brain natriuretic peptide, cardiac troponin-I, interleukin-18, liver fatty acid binding protein, kidney injury molecule-1, and neutrophil gelatinase associated lipocalin. Thus, peri-operative plasma H-FABP levels may be used for risk-stratification of AKI and mortality following cardiac surgery. PMID:25830762
Jayaraman, Rajesh; Sunder, Sham; Sathi, Satyanand; Gupta, Vijay Kumar; Sharma, Neera; Kanchi, Prabhu; Gupta, Anurag; Daksh, Sunil Kumar; Ram, Pranith; Mohamed, Ashik
Background: Acute kidney injury (AKI) is common after cardiac surgery, the incidence varying between 7.7% and 28.1%. It significantly increases morbidity and mortality. Creatinine considerably delays the diagnosis with its own attended demerits. Novel urinary biomarkers are emerging which help in rapid diagnosis thus reducing the morbidity and mortality. Biomarkers of our study were neutrophil gelatinase-associated lipocalin (NGAL) and Interleukin-18 (IL-18). Objectives: To find out the incidence of AKI in post-cardiac surgery patients in our hospital, the ability of the two biomarkers in early diagnosis in predicting the severity of AKI based on RIFLE’s criteria and their ability to discriminate pre-renal from intrinsic AKI. Patients and Methods: One-hundred patients who underwent cardiac surgery were selected. Midstream urine samples were collected at 3 time intervals (baseline before surgery, 24 hours and 7 days after surgery). Biomarkers were measured by ELISA using BIORAD processors. Fractional excretion of sodium and urea were used to discriminate pre-renal from intrinsic AKI. Results: Out of 100 patients, 31 had AKI, 11 being pre-renal and 20 intrinsic AKI. Four patients required renal replacement therapy (12.9% among AKI cases and 4% in the overall study cohort). Four among 31 expired in intensive care unit. Identifiable risk factors for AKI included insulin requiring diabetes mellitus, chronic obstructive pulmonary disease, increased cardio-pulmonary bypass time, combined valvular surgery and coronary artery bypass grafting, employment of intra-aortic balloon counter pulsation, left main coronary artery occlusion and an ejection fraction of < 40%. NGAL was extremely sensitive (area under curve-0.96) in detecting intrinsic AKI at 24 hours followed by IL-18 ratio with an area under curve of 0.89. Creatinine at 24 hours was able to detect only 31.6% of intrinsic AKI. None of the pre-renal cases showed rise in the urinary biomarker levels. Patients with
Schreck, David M; Fishberg, Robert D
The objective of this study us to stratify by gender a new cardiac electrical biomarker (CEB) diagnostic accuracy for detection of acute myocardial ischemic injury (AMII). This is a noninferiority retrospective, case-control, blinded study of 310 archived measured electrocardiograms (ECGs) acquired from 218 men and 92 women. The CEB is constructed from the derived ECG (dECG) synthesized from 3 leads. Electrocardiograms were included if acquired less than or equal to 1 day from patient presentation. Electrocardiograms were interpreted by 2 blinded physicians and adjudicated by consensus. Standard ST analyses and computerized ECG interpretations were active controls. Electrocardiograms were excluded for noise and baseline wander, age younger than 18 years, and ectopic beats in the 10-second ECG acquisition. Diagnostic accuracy measures of sensitivity, specificity, positive and negative predictive values, and likelihood ratios were stratified by gender. Measured vs derived ECG correlations were quantitatively compared using Pearson correlation and qualitatively by percent agreement methodology. The CEB sensitivities for AMII detection in men and women were 93.9% and 90.5%, respectively, and CEB specificities were 90.7% and 95.2%, respectively, and were superior to active controls. Derived and measured ECGs showed high correlation for both men and women with r = 0.857 and r = 0.893, respectively. Reference standard intra-agreement analysis for measured ECGs and dECGs with AMII was 99.4%. The CEB demonstrates high diagnostic accuracy for detection of AMII in men and women. The ECG can be derived with accuracy from 3 leads. This technology is an efficient real-time method of identifying patients with AMII who are being monitored in acute care settings. Copyright © 2014 Elsevier Inc. All rights reserved.
Ho, Julie; Reslerova, Martina; Gali, Brent; Nickerson, Peter W; Rush, David N; Sood, Manish M; Bueti, Joe; Komenda, Paul; Pascoe, Edward; Arora, Rakesh C; Rigatto, Claudio
After heart surgery, acute kidney injury (AKI) confers substantial long-term risk of death and chronic kidney disease. We hypothesized that small changes in serum creatinine (SCr) levels measured within a few hours of exit from the operating room could help discriminate those at low versus high risk of AKI. Prospective cohort of 350 elective cardiac surgery patients (valve or coronary artery bypass grafting) recruited in Winnipeg, Canada. Baseline SCr level was obtained at the preoperative visit 2 weeks before surgery. The postoperative SCr level was drawn within 6 hours of completion of surgery and then daily while the patient was in the hospital. Immediate (ie, <6 hours) postoperative SCr level change (ΔSCr), categorized as within 10% (reference), decrease >10%, or increase >10% relative to baseline. AKI, defined according to the new KDIGO (Kidney Disease: Improving Global Outcomes) consensus definition as an increase in SCr level >0.3 mg/dL within 48 hours or >1.5 times baseline within 1 week. We compared the C statistic of logistic models with and without inclusion of immediate postoperative ΔSCr. After surgery, 176 patients (52%) experienced a decrease >10% in SCr level, 26 (7.4%) experienced an increase >10%, and 143 had ΔSCr within ±10% of baseline. During hospitalization, 53 (14%) developed AKI. Bypass pump time, baseline estimated glomerular filtration rate, and European System for Cardiac Operative Risk Evaluation (euroSCORE) were associated with AKI in a parsimonious base logistic model. Added to the base model, immediate postoperative ΔSCr was associated strongly with subsequent AKI and significantly improved model discrimination over the base model (C statistic, 0.78 [95% CI, 0.71-0.85] vs 0.69 [95% CI, 0.62-0.77]; P < 0.001). A ≥10% SCr level decrease predicted significantly lower AKI risk (OR, 0.37; 95% CI, 0.18-0.76), whereas a ≥10% SCr level increase predicted significantly higher (OR, 6.38; 95% CI, 2.37-17.2) AKI risk compared with the
Tobey, Rajika; Cheng, Hao; Gao, Mei; Li, Zhongmin; Young, J Nilas; Boyd, W Douglas; Ji, Fuhai; Liu, Hong
This study assessed the effect of 2 types of hydroxyethyl starches (HES) on renal integrity and blood transfusion in cardiac surgery patients. Retrospective investigation. Patients from a single tertiary medical center. Inclusion criteria included coronary artery bypass graft (CABG) and/or valve surgery that included cardiopulmonary bypass with aortic cross-clamping. Intraoperative HES and blood product administration. The study comprised 1,265 patients who met inclusion criteria. Of these patients, 70% received HES, and of these, 47% received<1,000 mL and 53% received≥1,000 mL. There was no difference in the development of acute kidney injury between the 2 groups. A parsimonious propensity model for colloids showed that combined CABG and valve surgery were less likely to be associated with HES administration than was CABG alone (OR 0.68, confidence interval [CI] 0.46-0.97; p = 0.04). Intra-aortic balloon pump use was less likely to be associated with HES administration (OR 0.57, CI 0.38-0.86; p = 0.007). Patients with chronic kidney disease, stages 3 to 5, were less likely to receive HES, with an OR of 0.56 (CI 0.38-0.84; p = 0.004); 0.51 (CI 0.20-1.33; p = 0.170); and 0.23 (CI 0.12-0.44; p<0.0001), respectively, for each stage. No difference was noted in red blood cell transfusion. However, fresh frozen plasma, cryoprecipitate, and platelet transfusions were significantly higher with larger volumes of HES, with an OR of 2.03 (CI 1.64-2.52; p<0.001); 1.60 (CI 1.30-1.97; p<0.000); and 1.62 (CI 1.21-2.15; p = 0.006), respectively. No differences in surgical mortality were found between the colloid and noncolloid groups. This study showed no association of postoperative acute kidney injury and red blood cell transfusion between the colloid and noncolloid groups. Although the complication rate was higher with HES administration, there was no difference in surgery mortality between the 2 groups. Copyright © 2017 Elsevier Inc. All rights reserved.
Dongworth, R K; Mukherjee, U A; Hall, A R; Astin, R; Ong, S-B; Yao, Z; Dyson, A; Szabadkai, G; Davidson, S M; Yellon, D M; Hausenloy, D J
Novel therapeutic targets are required to protect the heart against cell death from acute ischemia-reperfusion injury (IRI). Mutations in the DJ-1 (PARK7) gene in dopaminergic neurons induce mitochondrial dysfunction and a genetic form of Parkinson's disease. Genetic ablation of DJ-1 renders the brain more susceptible to cell death following ischemia-reperfusion in a model of stroke. Although DJ-1 is present in the heart, its role there is currently unclear. We sought to investigate whether mitochondrial DJ-1 may protect the heart against cell death from acute IRI by preventing mitochondrial dysfunction. Overexpression of DJ-1 in HL-1 cardiac cells conferred the following beneficial effects: reduced cell death following simulated IRI (30.4±4.7% with DJ-1 versus 52.9±4.7% in control; n=5, P<0.05); delayed mitochondrial permeability transition pore (MPTP) opening (a critical mediator of cell death) (260±33 s with DJ-1 versus 121±12 s in control; n=6, P<0.05); and induction of mitochondrial elongation (81.3±2.5% with DJ-1 versus 62.0±2.8% in control; n=6 cells, P<0.05). These beneficial effects of DJ-1 were absent in cells expressing the non-functional DJ-1(L166P) and DJ-1(Cys106A) mutants. Adult mice devoid of DJ-1 (KO) were found to be more susceptible to cell death from in vivo IRI with larger myocardial infarct sizes (50.9±3.5% DJ-1 KO versus 41.1±2.5% in DJ-1 WT; n≥7, P<0.05) and resistant to cardioprotection by ischemic preconditioning. DJ-1 KO hearts showed increased mitochondrial fragmentation on electron microscopy, although there were no differences in calcium-induced MPTP opening, mitochondrial respiratory function or myocardial ATP levels. We demonstrate that loss of DJ-1 protects the heart from acute IRI cell death by preventing mitochondrial dysfunction. We propose that DJ-1 may represent a novel therapeutic target for cardioprotection.
Varela, Carlos Federico; Greloni, Gustavo; Schreck, Carlos; Bratti, Griselda; Medina, Angel; Marenchino, Ricardo; Pizarro, Rodolfo; Belziti, Cesar; Rosa-Diez, Guillermo
Acute kidney injury (AKI) is a common complication after cardiac surgery (CS). Recently, neutrophil gelatinase-associated lipocalin (NGAL) was shown to predict AKI development earlier than serum creatinine, but it is not widely used in clinical practice. Fractional excretion of urea (FeU) has been referred to as a useful tool to discriminate between prerenal and established AKI. The aim of our study is to evaluate the sensitivity and specificity of FeU, in the early diagnosis of AKI in patients undergoing CS. We performed a prospective study on adults undergoing CS. AKI was defined by AKIN criteria. Individuals suffering from CKD, were excluded. Sensitivity and specificity of FeU, fractional excretion of sodium (FeNa) and urine NGAL, measured at 1, 6 and 24 h following CS, were assessed. We included 66 patients (26% female) aging 68 ± 11 years. AKI prevalence was 24% and mortality was 3.28%. Patients with AKI had a significantly lower FeU compared to those without AKI (23.89 ± 0.67% vs. 34.22 ± 0.58%; p < 0.05) 6 h after CS, but not at the 1- and 24-h time points. NGAL was also statistically significant between both groups. FeU showed a 75% sensitivity and 79.5% specificity; the AUC was 0.786. ROC analysis of FeU and NGAL yielded similar values (p = NS). FeU is useful as an early biomarker to predict AKI after CS and it is comparable to the new biomarker NGAL.
Xie, Xiangcheng; Wan, Xin; Ji, Xiaobing; Chen, Xin; Liu, Jian; Chen, Wen; Cao, Changchun
Objective To evaluate the incidence, risk, or protective factors of acute kidney injury (AKI) in patients after cardiac surgery based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Methods A retrospective analysis of 2,575 patients undergoing their first documented cardiac surgery with cardiopulmonary bypass (CPB) was conducted. Perioperative variables were collected and analyzed. Univariate and multiple logistic regression models were used for determining the association between the development of AKI and risk factors. Multiple Cox-proportional hazards modeling was performed to evaluate the impact of AKI on the mortality in the intensive care unit and hospital length of stay. Results Of 2,575 patients, 931 (36%) developed AKI. A total of 30 (1.2%) patients required renal replacement therapy. In the multivariate analysis, mechanical ventilation duration (OR1.446, 95% CI 1.195-1.749, p<0.001), CPB duration of ≥110 min (OR 1.314, 95% CI 1.072-1.611, p=0.009), erythrocytes transfusion (OR 1.078, 95% CI 1.050-1.106, p<0.001), and postoperative body temperature greater than 38℃ within 3 days (OR 1.234, 95% CI 1.018-1.496, p=0.032) were independent risk factors for CSA-AKI, while ulinastatin use was associated with a reduced incidence of CSA-AKI (OR 0.694, 95% CI 0.557-0.881, p=0.006). CSA-AKI was significantly associated with in-hospital mortality (adjusted HR: 2.218, 95% CI 1.161-4.238, p=0.016), especially in patients needing renal replacement therapy (adjusted HR: 18.683, 95% CI 8.579-40.684, p<0.001). Conclusion Mechanical ventilation duration, erythrocytes transfusion, and postoperative body temperature above 38℃ within 3 days were considered independent risk factors for CSA-AKI. The use of ulinastatin was associated with a reduced incidence of CSA-AKI. PMID:28154270
Kawahara, Eisuke; Ikeda, Satoshi; Miyahara, Yoshiyuki; Kohno, Shigeru
Electrocardiographic abnormalities, cardiac injury, and autonomic nervous function were investigated in patients with acute-phase subarachnoid hemorrhage (SAH) (42 patients with SAH related to ruptured aneurysm and 42 control subjects). Electrocardiogram and Holter electrocardiogram for spectral analysis of heart rate variability (HRV) were recorded. Concentrations of cardiogenic enzymes (ie, creatine kinase-myocardial fraction [CK-MB], myosin light chain I, and troponin T), plasma concentrations of catecholamine (ie, noradrenaline, adrenaline, 3-methoxy-4-hydroxy-phenylethylene glycol [MHPG]) and HRV were compared in the acute and chronic phase of SAH, and with the values in the controls subjects. As previously reported, patients with acute SAH exhibited electrocardiographic (ECG) abnormalities and increased concentrations of both cardiogenic enzymes and plasma catecholamines, suggesting that acceleration of sympathetic activity is involved. However, HRV analysis showed enhanced parasympathetic activity, probably associated with increased intracranial pressure after the onset of SAH, which may be explained by accentuated antagonism, negative feedback of noradrenaline to the center, and reduction of sympathetic activity after reaching a peak level. The results suggest that not only sympathetic activity but also vagal activity is enhanced during the acute phase of SAH, thus contributing to the ECG abnormalities and the onset of cardiac injury.
Mossanen, Jana C.; Pracht, Jessica; Jansen, Tobias U.; Buendgens, Lukas; Stoppe, Christian; Goetzenich, Andreas; Struck, Joachim; Autschbach, Rüdiger; Marx, Gernot; Tacke, Frank
Acute kidney injury (AKI) develops in up to 40% of patients after cardiac surgery. The soluble urokinase plasminogen activator receptor (suPAR) has been identified as a biomarker for incident chronic kidney disease (CKD). Proenkephalin (proENK) also has been shown to be a biomarker for renal dysfunction. We hypothesized that pre-surgery suPAR and proENK levels might predict AKI in patients undergoing cardiac surgery. Consecutive patients (n = 107) undergoing elective cardiac surgery were studied prospectively. Clinical data, laboratory parameters, suPAR and proENK serum levels were assessed before operation, after operation and days one and four post-operatively. A total of 21 (19.6%) patients developed AKI within the first four days after elective surgery. Serum levels of suPAR and proENK, but not of creatinine, were significantly higher before surgery in these patients compared to those patients without AKI. This difference remained significant for suPAR, if patients with or without AKI were matched for risk factors (hypertension, diabetes, CKD). If cardiac surgery patients with pre-existing CKD (n = 10) were excluded, only pre-operative suPAR but not proENK serum levels remained significantly elevated in patients with subsequent AKI. Thus, our findings indicate that suPAR may be a predictive biomarker for AKI in the context of cardiac surgery, even in patients without underlying CKD. PMID:28758975
Serpooshan, Vahid; Ruiz-Lozano, Pilar
Considering the impaired regenerative capacity of adult mammalian heart tissue, cardiovascular tissue engineering aims to create functional substitutes that can restore the structure and function of the damaged cardiac tissue. The success of cardiac regenerative therapies has been limited mainly due to poor control on the structure and properties of the tissue substitute, lack of vascularization, and immunogenicity. In this study we introduce a new approach to rapidly engineer dense biomimetic scaffolds consisting of type I collagen, to protect the heart against severe ischemic injury. Scaffold biomechanical properties are adjusted to mimic embryonic epicardium which is shown to be optimal to support cardiomyocyte contractile work. Moreover, the designed patch can serve as a delivery device for targeted, controlled release of cells or therapeutic macromolecules into the lesion area.
Billings, Frederic T.; Hendricks, Patricia A.; Schildcrout, Jonathan S.; Shi, Yaping; Petracek, Michael R.; Byrne, John G.; Brown, Nancy J.
Importance Hydroxy-methylglutaryl-coenzyme A reductase inhibitors affect several mechanisms underlying acute kidney injury (AKI). Objective To test the hypothesis that short-term high-dose perioperative atorvastatin would reduce AKI following cardiac surgery Design, Setting, Participants Double-blinded, placebo-controlled, randomized trial of adult cardiac surgery patients conducted November 2009 to October 2014 at Vanderbilt University Medical Center Intervention Statin-naïve patients (n=199) were randomly assigned 80mg atorvastatin the day before surgery, 40mg the morning of surgery, and 40mg daily following surgery (n=102) or matching placebo (n=97). Patients using statins prior to study enrollment (n=416) continued their pre-enrollment statin until the day of surgery, were randomly assigned 80mg atorvastatin the morning of surgery and 40mg the morning after (n=206) or matching placebo (n=210), and resumed their statin on postoperative day 2. Main Outcome AKI, defined as 0.3 mg/dl rise in serum creatinine within 48 hours of surgery (AKIN criteria) Results The DSMB recommended stopping the statin-naïve group due to increased AKI among statin-naïve participants with chronic kidney disease (CKD, estimated glomerular filtration rate <60 ml/min/1.73 m2) receiving atorvastatin and then recommended stopping for futility after 615 participants (median age, 67 years; 188 [30.6%] women, and 202 [32.8%] diabetic) completed the study. Among all participants (n=615), AKI occurred in 64 of 308 participants (20.8%) randomized to atorvastatin versus 60 of 307 participants (19.5%) randomized to placebo (risk ratio [RR], 1.06 [95% CI, 0.78–1.46]; P=0.75). Among statin-naïve participants (n=199), AKI occurred in 22 of 102 (21.6%) receiving atorvastatin versus 13 of 97 (13.4%) receiving placebo (RR, 1.61 [0.86–3.01]; P=0.15), and serum creatinine increased 0.11mg/dl (−0.11 to 0.56) (median [10th to 90th percentile]) in those randomized to atorvastatin versus 0.05 (−0
Chin, Jocelyn T.; Troke, Joshua J.; Kimura, Naoyuki; Itoh, Satoshi; Wang, Xi; Palmer, Owen P.; Robbins, Robert C.; Fischbein, Michael P.
The main cause of mortality after the first year from cardiac transplantation is cardiac allograft vasculopathy (CAV), which leads to chronic rejection of the heart. To improve long-term outcomes in cardiac transplantation, treatments to prevent or diminish CAV are actively being researched. Ischemia-reperfusion (I-R) injury has been shown to be the strongest alloantigen-independent factor in the development of CAV. Here, we investigate the use of metformin in murine cardiac transplantation models as a novel cardioprotective agent to limit acute I-R injury and subsequent chronic rejection. We show that metformin treatment activates AMP-activated kinase (AMPK) in vitro and in vivo. In the acute transplantation model, metformin activation of AMPK resulted in significantly decreased apoptosis in cardiac allografts on postoperative day (POD) 1 and 8. In the chronic transplantation model, metformin pretreatment of allografts led to significantly improved graft function and significantly decreased CAV, as measured on POD 52. Taken together, our results in the acute and chronic rejection studies suggest a potential cardioprotective mechanism for metformin; we demonstrate a correlation between metformin-induced decrease in acute I-R injury and metformin-related decrease in chronic rejection. Thus, one of the ways by which metformin and AMPK activation may protect the transplanted heart from chronic rejection is by decreasing initial I-R injury inherent in donor organ preservation and implantation. Our findings suggest novel therapeutic strategies for minimizing chronic cardiac rejection via the use of metformin- and AMPK-mediated pathways to suppress acute I-R injury. PMID:22180679
Chin, Jocelyn T; Troke, Joshua J; Kimura, Naoyuki; Itoh, Satoshi; Wang, Xi; Palmer, Owen P; Robbins, Robert C; Fischbein, Michael P
The main cause of mortality after the first year from cardiac transplantation is cardiac allograft vasculopathy (CAV), which leads to chronic rejection of the heart. To improve long-term outcomes in cardiac transplantation, treatments to prevent or diminish CAV are actively being researched. Ischemia-reperfusion (I-R) injury has been shown to be the strongest alloantigen-independent factor in the development of CAV. Here, we investigate the use of metformin in murine cardiac transplantation models as a novel cardioprotective agent to limit acute I-R injury and subsequent chronic rejection. We show that metformin treatment activates AMP-activated kinase (AMPK) in vitro and in vivo. In the acute transplantation model, metformin activation of AMPK resulted in significantly decreased apoptosis in cardiac allografts on postoperative day (POD) 1 and 8. In the chronic transplantation model, metformin pretreatment of allografts led to significantly improved graft function and significantly decreased CAV, as measured on POD 52. Taken together, our results in the acute and chronic rejection studies suggest a potential cardioprotective mechanism for metformin; we demonstrate a correlation between metformin-induced decrease in acute I-R injury and metformin-related decrease in chronic rejection. Thus, one of the ways by which metformin and AMPK activation may protect the transplanted heart from chronic rejection is by decreasing initial I-R injury inherent in donor organ preservation and implantation. Our findings suggest novel therapeutic strategies for minimizing chronic cardiac rejection via the use of metformin- and AMPK-mediated pathways to suppress acute I-R injury.
Brown, Jeremiah R.; Kramer, Robert S.; Coca, Steven G.; Parikh, Chirag R.
Abstract: Previously, we reported that the addition of duration to the Acute Kidney Injury Network (AKIN) definition of acute kidney injury (AKI) is a marker for more severe kidney injury and predicts long-term mortality. We aimed to evaluate an example of the utility of adding AKI duration to the AKIN definition by comparing the historical use of aprotinin with Amicar. In a single-center observational study, we followed 4987 consecutive patients undergoing cardiac surgery between 2002 and 2007 for postsurgery AKI. Patients with a history of hemodialysis were excluded. Duration of AKI was calculated by the number of days AKI was present as defined by a ≥0.3 (mg/dL) or a ≥50% increase in serum creatinine from baseline or new onset of acute dialysis. Kaplan-Meier and Cox’s proportional hazard modeling was conducted to evaluate 5-year mortality. Fifty-three percent of patients received Amicar (n = 2333) and 47% received high-dose aprotinin (n = 2093). Patients receiving aprotinin had evidence of more advanced disease and comorbidity and were more likely to develop AKI and have longer durations of AKI than Amicar (p < .001): 7.0 ± 11.5 vs. 3.8 ± 6.0 days (p < .001). Nearest-neighbor propensity matching demonstrated aprotinin had significantly worse 5-year mortality compared with Amicar (relative risk [RR] = 2.09, 95% confidence interval [CI] = 1.65–2.65). AKI duration added to the AKIN definition of AKI may provide the necessary sensitivity and specificity for evaluating renal outcomes in clinical trials. PMID:22416602
Coca, Steven G.; Garg, Amit X.; Swaminathan, Madhav; Garwood, Susan; Hong, Kwangik; Thiessen-Philbrook, Heather; Passik, Cary; Koyner, Jay L.; Parikh, Chirag R.; Jai, Raman; Jeevanandam, Valluvan; Akhter, Shahab; Devarajan, Prasad; Bennett, Michael; Edelsteinm, Charles; Patel, Uptal; Chu, Michael; Goldbach, Martin; Guo, Lin Ruo; McKenzie, Neil; Myers, Mary Lee; Novick, Richard; Quantz, Mac; Zappitelli, Michael; Dewar, Michael; Darr, Umer; Hashim, Sabet; Elefteriades, John; Geirsson, Arnar
Background Using either an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) the morning of surgery may lead to ‘functional’ postoperative acute kidney injury (AKI), measured by an abrupt increase in serum creatinine. Whether the same is true for ‘structural’ AKI, measured with new urinary biomarkers, is unknown. Methods The TRIBE-AKI study was a prospective cohort study of 1594 adults undergoing cardiac surgery at six hospitals between July 2007 and December 2010. We classified the degree of exposure to ACEi/ARB into three categories: ‘none’ (no exposure prior to surgery), ‘held’ (on chronic ACEi/ARB but held on the morning of surgery) or ‘continued’ (on chronic ACEi/ARB and taken the morning of surgery). The co-primary outcomes were ‘functional’ AKI based upon changes in pre- to postoperative serum creatinine, and ‘structural AKI’, based upon peak postoperative levels of four urinary biomarkers of kidney injury. Results Across the three levels (none, held and continued) of ACEi/ARB exposure there was a graded increase in functional AKI, as defined by AKI stage 1 or worse; (31, 34 and 42%, P for trend 0.03) and by percentage change in serum creatinine from pre- to postoperative (25, 26 and 30%, P for trend 0.03). In contrast, there were no differences in structural AKI across the strata of ACEi/ARB exposure, as assessed by four structural AKI biomarkers (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, interleukin-18 or liver-fatty acid-binding protein). Conclusions Preoperative ACEi/ARB usage was associated with functional but not structural acute kidney injury. As AKI from ACEi/ARB in this setting is unclear, interventional studies testing different strategies of perioperative ACEi/ARB use are warranted. PMID:24081864
Mejri, Mohamed A; Yousfi, Narimen; Hammouda, Omar; Tayech, Amel; Ben Rayana, Mohamed C; Driss, Tarak; Chaouachi, Anis; Souissi, Nizar
The aim of this study was to evaluate the effect of two types of partial sleep deprivation (PSD) on biomarkers of muscle and cardiac injuries in response to acute intermittent exercise in professional athletes. In a counterbalanced order, ten healthy male Taekwondo athletes were asked to perform the Yo-Yo Intermittent Recovery Test (YYIRT) in three conditions, allowing a 36 h recovery period in between: 1) following a full night of habitual sleep known as a reference sleep night (RN); 2) following PSD in the beginning of the night (PSDBN); and 3) following PSD in the end of the night (PSDEN). Heart rate (HR) and arterial oxygen saturation (SaO2) were measured during exercise. Blood samples were taken just before and 3 min after the YYIRT to measure biomarkers related to muscle and cardiac injuries (BRMCI). No significant effect of PSD was observed for physiological parameters (i.e., HR and SaO2). However, a significant alteration of resting ultra-sensitive C-reactive protein (us-CRP) (P<0.05) and myoglobin (MYO) (P<0.01) levels was detected after PSDEN. Furthermore, all BRMCI were altered by exercise. Likewise, compared to RN, PSD affected creatine phosphokinase (CPK) and MYO levels in response to exercise (P<0.05). The present study indicates that PSDEN increase the resting us-CRP and MYO levels, and that the two types of PSD increase the CPK and MYO levels in response to acute intermittent exercise, among Taekwondo athletes, in the evening of the following day. However, no rise of the physiological responses has been observed after the two types of PSD, at rest and in response to the exercise.
Mutoh, Tomoko; Mutoh, Tatsushi; Nakamura, Kazuhiro; Yamamoto, Yukiko; Tsuru, Yoshiharu; Tsubone, Hirokazu; Ishikawa, Tatsuya; Taki, Yasuyuki
Early brain injury/ischemia (EBI) is a serious complication early after subarachnoid hemorrhage (SAH) that contributes to development of delayed cerebral ischemia (DCI). This study aimed to determine the role of inotropic cardiac support using milrinone (MIL) on restoring acute cerebral hypoperfusion attributable to EBI and improving outcomes after experimental SAH. Forty-three male C57BL/6 mice were assigned to either sham surgery (SAH-sham), SAH induced by endovascular perforation plus postconditioning with 2% isoflurane (Control), or SAH plus isoflurane combined with MIL with and without hypoxia-inducible factor inhibitor (HIF-I) pretreatment. Cardiac output (CO) during intravenous MIL infusion (0.25-0.75 μg/kg/min) between 1.5 and 2.5h after SAH induction was monitored with Doppler-echocardiography. MRI-continuous arterial spin labeling was used for quantitative CBF measurements. Neurobehavioral function was assessed daily by neurological score and open field test. DCI was analyzed 3 days later by determining infarction on MRI. Mild reduction of cardiac output (CO) and global cerebral blood flow (CBF) depression were notable early after SAH. MIL increased CO in a dose-dependent manner (P <0.001), which was accompanied by improved hypoperfusion, incidence of DCI and functional recovery than Control (P <0.05). The neuroprotective effects afforded by MIL or Control were attenuated by HIF inhibition (P <0.05). These results suggest that MIL improves acute hypoperfusion by its inotropic effect, leading to neurobehavioral improvement in mice after severe SAH, in which HIF may be acting as a critical mediator. This article is protected by copyright. All rights reserved.
Saeed, Maythem; Hetts, Steven W; Do, Loi; Wilson, Mark W
To use cardiac magnetic resonance (MR) imaging indices, injury biomarkers, and microscopy for quantifying the effects of defined microemboli volume and sizes on viability, left ventricular (LV) function, and perfusion in preexisting acute myocardial infarcts in a swine model. Institutional approval was obtained to perform x-ray fluoroscopy and 90-minute left anterior descending coronary artery occlusion-reperfusion (single ischemic insult) in 16 pigs and coronary embolization in eight of the 16 pigs (32 mm(3), 40-120 μm microemboli) (double ischemic insults). Another eight pigs served as controls. Cardiac MR imaging results (viability, function, and perfusion), injury biomarkers (creatine-kinase-MB and troponin I), and histopathologic evaluations were quantified. Analysis of variance was performed, and a P value less than .02 was considered to indicate a significant difference. Delayed contrast material-enhanced MR imaging allowed simultaneous visualization of hyperenhanced large infarcts, hypoenhanced microvascular obstruction (MVO) zones, and moderately enhanced patchy microinfarcts in border zones, which represent different degrees of contraction and perfusion in the respective regions, in pigs subjected to double ischemic insults. The increase in myocardial damage was smaller in pigs with double insults (15.7% ± 1.1% of total LV mass) than in those with a single insult (12.4% ± 1.2%, P < .02), but the reduction in LV ejection fraction was disproportional (32% ± 0.6% and 38% ± 1%, P < .02, respectively). Delayed contrast-enhanced imaging can allow quantification of the MVO zone but can result in underestimation of the extent of myocardial damage compared with microscopy in animals subjected to double insults (18.2 ± 1.6, P < .02). A significant increase in cardiac injury biomarkers was observed at 18-24 hours in both cohorts. The additional effect of microemboli on troponin I was demonstrated at 68-72 hours (3.2 ng/mL ± 0.85 [3.20 μg/L ± 0.85] vs 1
Takaki, Shunsuke; Shehabi, Yahya; Pickering, John W; Endre, Zoltan; Miyashita, Tetsuya; Goto, Takahisa
Acute kidney injury is common following cardiac surgery. Experimental models of acute kidney injury suggest that successful therapy should be implemented within 24-48 h of renal injury. However, it is difficult to detect acute kidney injury shortly after cardiac surgery, because creatinine concentration is diluted by cardiopulmonary bypass. We hypothesized that, following cardiopulmonary bypass, creatinine reduction ratios would correlate with haematocrit reduction ratios and would be associated with the incidence of acute kidney injury. We collected demographic and blood test data from consecutive patients (n = 1137) who had undergone cardiac surgery with cardiopulmonary bypass. The creatinine reduction ratio was calculated as follows: (preoperative creatinine-postoperative creatinine)/preoperative creatinine. Patients were assigned to either of two groups. The first group (Group 1) was used to determine the threshold for acute kidney injury, and the second group (Group 2) was used to assess diagnostic performance. Acute kidney injury was defined as an increase in serum creatinine level >0.3 mg/dl or >150% from baseline. The incidence of acute kidney injury was 14.5% (79/545) in Group 1 and 15.5% (92/592) in Group 2. Postoperatively, creatinine concentration correlated strongly with haematocrit concentration (Pearson's r(2): 0.91). In Group 1, the area under the receiver operating characteristic curve, sensitivity and specificity were 0.71, 64.1 and 66.4%, respectively, for creatinine reduction ratios of <20%. In Group 2, the odds ratio, positive predictive value, negative predictive value and relative risk for creatinine reduction ratio performance were 4.3 (95% confidence interval 2.6-7.0), 0.27 (0.21-0.32), 0.92 (0.89-0.95) and 3.42 (2.22-5.27), respectively. The creatinine reduction ratio may be associated with perioperative renal injury. Therefore, it is a good diagnostic indicator with high performance, and may be useful in detecting acute kidney injury at
Haase-Fielitz, Anja; Bellomo, Rinaldo; Devarajan, Prasad; Story, David; Matalanis, George; Dragun, Duska; Haase, Michael
To compare the value of novel with conventional serum biomarkers in the prediction of acute kidney injury (AKI) in adult cardiac surgical patients according to preoperative renal function. Single-center, prospective observational study. Tertiary hospital. One hundred adult cardiac surgical patients. We measured concentrations of plasma neutrophil gelatinase-associated lipocalin (NGAL), and serum cystatin C, and creatinine and urea at baseline, on arrival in the intensive care unit (ICU) and at 24 hours postoperatively. We assessed such biomarkers in relation to the development of AKI (>50% increase in creatinine from baseline) and to a composite end point (need for renal replacement therapy and in-hospital mortality). We defined an area under the receiver operating characteristic curve of 0.60-0.69 as poor, 0.70-0.79 as fair, 0.80-0.89 as good, and 0.90-1.00 as excellent in terms of predictive value. On arrival in ICU, plasma NGAL and serum cystatin C were of good predictive value, but creatinine and urea were of poor predictive value. After exclusion of patients with preoperative renal impairment (estimated glomerular filtration rate <60 mL/min), the predictive performance for AKI of all renal biomarkers on arrival in ICU remained unchanged except for cystatin C, which was of fair value in such patients. At 24 hours postoperatively, all renal biomarkers were of good predictive value. On arrival in ICU, novel biomarkers were superior to conventional biomarkers (p < 0.05). Plasma NGAL (p = 0.015) and serum cystatin C (p = 0.007) were independent predictors of AKI and of excellent value in the prediction of the composite end point. Early postoperative measurement of plasma NGAL was of good value in identifying patients who developed AKI after adult cardiac surgery. Plasma NGAL and serum cystatin C were superior to conventional biomarkers in the prediction of AKI and were also of prognostic value in this setting.
Singh, Gurkeerat; Sabath, Bruce
An 84-year-old man with hypertension and a history of deep venous thrombosis (on warfarin) was admitted with shortness of breath presumed to be due to congestive heart failure. Echocardiogram performed the following day showed a low-normal ejection fraction with signs of elevated right-sided pressures but was otherwise normal. He improved with diuretic therapy but after a few days was found to be hypotensive with a concomitant rise in creatinine with decreased urine output. This was felt to be secondary to over-diuresis but he did not respond to small boluses of intravenous fluids as his kidney function continued to worsen and hypotension persisted. He was transferred to the intermediate care unit where a rapid, bedside ultrasound revealed a new, moderate-sized pericardial effusion with tamponade physiology. Pericardiocentesis, with removal of 750 cc of frank blood, led to dramatic improvement in blood pressure, kidney function, and urine output. Here, we demonstrate the utility of point-of-care ultrasound in a community hospital setting where urgent echocardiogram is not routinely available. We also report acute kidney injury due to pericardial tamponade reversed with therapeutic pericardiocentesis. PMID:27124173
Eremenko, A A; Minbolatova, N M
Acute kidney injury can greatly increase the severity of multiple organ dysfunction syndrome (MODS) and impair patient outcomes. To study the clinical significance of acute kidney injury in patients with MODS in early postoperative period after cardiac surgety and its influence, on the severity of the patient condition and outcomes. The study involved 117 patients aged 57.2 ± 1.2 years. The Group 1, control, included 74 patients with uncomplicated postoperative period; the Group 2--43 patients with MODS, who were divided into the survivors (33 patients, group 2a) and deaths (10 patients, group 2b). In Group 2. thefollowingparaineters were higher--the volume of blood loss by 1.5 times (p = 0,001), the duration of the cardiopulmonary bypass 1.7 times (p 0.001), and aortic clamping 1.6 times (p = 0,001). Group 2a and 2b on these indicators did not differ Average scale Group 2b was 1,3-fold higher than in survivors (p = 0,001). Patients differ in the severity of the central nervous system disorders (the average score of Glasgow Coma Scale survivors was 1.3 times higher P = 0,001) and severity of acute kidney injury On a RIFLE scale patients of group 2a normal data was observed in 12%, the stage of risk in 61%, and damage in 27%. In 50% of the dead was a stage of disease (p = 0.04), the rest--damage. In the dynamics of the group 2b impaired renal and hepatic functions have progressed. By day 3 ASTwas on average 2-fold higher (p = 0.01), ALT (1.9 fold, p = 0,001), alkaline phosphatase 1.5 times (p = 0.001), while the total blood protein below 1.3 times (p = 0.00 1), than in group 2a. Creatinine in patients of Group 2b was 1.4 tunes higher (p = 0,036), urea 1.6 (p = 0.026), u-NGAL 7 times higher (p = 0.001), than in group 2a. Long cardiopulmonary bypass, clamping of the aorta and a large amount of perioperative the risk of MODS in the early postoperative period, but do not affect the outcome. On the background of the dzvelopment of MODS an average score on MODS-2 scale
Savluk, Omer Faruk; Guzelmeric, Fusun; Yavuz, Yasemin; Cevirme, Deniz; Gurcu, Emre; Ogus, Halide; Orki, Tulay; Kocak, Tuncer
Objective Acute kidney injury after cardiac surgery is associated with mortality and morbidity. Therefore, strategies to prevent acute kidney injury are very important. The aim of this placebo-controlled randomized double-blind study was to compare the prophylactic efficacy of N-Acetylcysteine and dopamine administration in patients with pre-existing moderate renal insufficiency who were undergoing cardiopulmonary bypass. Methods This study included 135 patients with pre-existing moderate renal insufficiency who were scheduled for coronary artery bypass grafting surgery. Serum creatinine and GFR were recorded preoperatively and on the first and second postoperative days. Results On the first and second postoperative days, the drugs used showed statistically significant differences among the creatinine groups (P<0.001). According to Tukey’s HSD, on the first and second PO, the creatinine of Group N, D and P were significantly different (P<0.001). On the first and second PO, the used drugs showed statistically significant differences among the effects of eGFR (P<0.001). According to Tukey’s HSD on the first postoperative day, the average eGFR score of Group N compared to D and P were significantly difference (P<0.001). On the second postoperative day, the eGFR of Group N and D showed no difference (P=0.37), but P showed a difference (P<0.001). Conclusion We found that the prophylactic use of intravenous N-Acetylcysteine had a protective effect on renal function, whereas the application of renal dose dopamine did not have a protective effect in patients with pre-existing moderate renal failure.
Perry, Tjörvi E.; Muehlschlegel, Jochen D.; Liu, Kuang-Yu; Fox, Amanda A.; Collard, Charles D.; Shernan, Stanton K.; Body, Simon C.
BACKGROUND Acute kidney injury (AKI) after coronary artery bypass graft (CABG) surgery is associated with increased postoperative morbidity and mortality. We hypothesized that increased plasma neutrophil gelatinase-associated lipocalin (NGAL) measured immediately after separating from cardiopulmonary bypass (CPB) would predict AKI after CABG surgery. METHODS In a retrospective observational study, we examined the value of plasma NGAL measured after CPB for predicting the risk of developing AKI (defined as a ≥50% increase in serum creatinine from preoperative levels) in 879 patients after CABG surgery using multivariable logistic regression. Area under the curve of receiver operating characteristic curves was analyzed to assess sensitivities, specificities, and cutoff points for postoperative plasma NGAL levels to predict AKI. RESULTS Seventy-five patients (8.6%) developed postoperative AKI. Plasma NGAL levels measured after CPB were higher in patients who subsequently developed AKI than in those who did not (AKI: 268.8 ng/mL [207.5–459.5 ng/mL], median [interquartile range], vs no AKI: 238.4 ng/mL [172.0–319.1 ng/mL]; P < 0.001) and remained higher through postoperative day 4. An optimal serum plasma NGAL cutoff of 353.5 ng/mL at the post-CPB time point had a sensitivity of 38.7%, specificity of 81.5%, and a positive predictive value of 16.3% for predicting AKI. In our multivariate regression model, post-CPB plasma NGAL levels >353.5 ng/mL were independently associated with postoperative AKI (odds ratio, 2.3; 95% confidence interval, 1.5–6.5; P = 0.002). CONCLUSION An early increase of post-CPB plasma NGAL is associated with AKI in adult patients undergoing CABG surgery, although the sensitivity is low. Therefore, assessing early plasma NGAL alone has limited utility for predicting AKI in this patient population. PMID:20435938
Spahillari, Aferdita; Parikh, Chirag R; Sint, Kyaw; Koyner, Jay L; Patel, Uptal D; Edelstein, Charles L; Passik, Cary S; Thiessen-Philbrook, Heather; Swaminathan, Madhav; Shlipak, Michael G
The primary aim of this study was to compare the sensitivity and rapidity of acute kidney injury (AKI) detection by cystatin C level relative to creatinine level after cardiac surgery. Prospective cohort study. 1,150 high-risk adult cardiac surgery patients in the TRIBE-AKI (Translational Research Investigating Biomarker Endpoints for Acute Kidney Injury) Consortium. Changes in serum creatinine and cystatin C levels. Postsurgical incidence of AKI. Serum creatinine and cystatin C were measured at the preoperative visit and daily on postoperative days 1-5. To allow comparisons between changes in creatinine and cystatin C levels, AKI end points were defined by the relative increases in each marker from baseline (25%, 50%, and 100%) and the incidence of AKI was compared based on each marker. Secondary aims were to compare clinical outcomes among patients defined as having AKI by cystatin C and/or creatinine levels. Overall, serum creatinine level detected more cases of AKI than cystatin C level: 35% developed a ≥25% increase in serum creatinine level, whereas only 23% had a ≥25% increase in cystatin C level (P < 0.001). Creatinine level also had higher proportions meeting the 50% (14% and 8%; P < 0.001) and 100% (4% and 2%; P = 0.005) thresholds for AKI diagnosis. Clinical outcomes generally were not statistically different for AKI cases detected by creatinine or cystatin C level. However, for each AKI threshold, patients with AKI confirmed by both markers had a significantly higher risk of the combined mortality/dialysis outcome compared with patients with AKI detected by creatinine level alone (P = 0.002). There were few adverse clinical outcomes, limiting our ability to detect differences in outcomes between subgroups of patients based on their definitions of AKI. In this large multicenter study, we found that cystatin C level was less sensitive for AKI detection than creatinine level. However, confirmation by cystatin C level appeared to identify a subset of
Xu, Jiaqi; Chen, Yuanhan; Liang, Xinling; Hu, Penghua; Cai, Lu; An, Shengli; Li, Zhilian; Shi, Wei
To investigate the impact of pre-operative uric acid on acute kidney injury (AKI) after cardiac surgery in elderly patients. Clinical data were collected from 936 elderly patients (age ≥ 60 years) undergoing cardiac surgery with cardiopulmonary bypass in Guangdong General Hospital between January 2005 and May 2011. The baseline serum creatinine was defined as the latest serum creatinine before surgery, and AKI was diagnosed according to RIFLE criteria. Patients were divided into three groups according to the sex-specific cutoff values of serum uric acid tertiles (group A: ≤ 384.65 µmol/L in men, and ≤ 354.00 µmol/L in women; group B:384.66-476.99 µmol/L in men and 354.01-437.96 µmol/L in women; group C: ≥ 477.00 µmol/L in men and ≥ 437.97 µmol/L in women). Multivariate logistic regression analysis was used to analyze the independent risk factors for AKI. Among 936 elderly patients, 576 cases (61.5%) developed AKI. Mean uric acid concentration was higher in AKI patients than in Non-AKI patients ( (436.6 ± 119.1) µmol/L vs. (398.0 ± 107.2) µmol/L, P < 0.001). The incidence of AKI was 56.1% (175/312) in group A, 56.3% (175/311) in group B, 72.2% (226/313) in group C (P < 0.001). Multiple logistic regression analysis showed that, after adjusted for age, gender, co-morbidities(hypertension, diabetes mellitus, cerebrovascular disease, chronic obstructive pulmonary disease), previous cardiac surgery, eGFR<60 ml×min(-1) ×1.73 m(-2), heart function ≥ 3 (NYHA), positive urine protein, combination of coronary artery bypass grafting and valvular surgery, cardiopulmonary bypass operation time, aortic cross-clamping time, pre-operative angiotensin converting enzyme inhibitor or angiotensin II receptor blockers and lipid-lowering drugs use, early postoperative angiotensin converting enzyme inhibitor or angiotensin II receptor blockers, diuretics and digoxin use, post-operation central venous pressure, risk of post operative AKI was significantly higher in
Spahillari, Aferdita; Parikh, Chirag R.; Sint, Kyaw; Koyner, Jay L.; Patel, Uptal D.; Edelstein, Charles L.; Passik, Cary S.; Thiessen-Philbrook, Heather; Swaminathan, Madhav; Shlipak, Michael G.
Background The primary aim of this study was to compare the sensitivity and rapidity of AKI detection by cystatin C relative to creatinine following cardiac surgery. Study Design Prospective cohort study Settings and Participants 1,150 high-risk, adult cardiac surgery patients in the TRIBE-AKI (Translational Research Investigating Biomarker Endpoints for Acute Kidney Injury) Consortium. Predictor Changes in serum creatinine and cystatin C Outcome Post-surgical incidence of AKI Measurements Serum creatinine and cystatin C were measured at the preoperative visit and daily on postoperative days 1–5. To allow comparisons between changes in creatinine and cystatin C, AKI endpoints were defined by the relative increases in each marker from baseline (25, 50 and 100%) and the incidence of AKI was compared based upon each marker. Secondary aims were to compare clinical outcomes among patients defined as having AKI by cystatin C and/or creatinine. Results Overall, serum creatinine detected more cases of AKI than cystatin C: 35% developed a ≥25% increase in serum creatinine, whereas only 23% had ≥25% increase in cystatin C (p < 0.001). Creatinine also had higher proportions meeting the 50% (14% and 8%, p<0.001) and 100% (4% and 2%, p=0.005) thresholds for AKI diagnosis. Clinical outcomes were generally not statistically different for AKI cases detected by creatinine or cystatin C. However, for each AKI threshold, patients with AKI confirmed by both markers had significantly higher risk of the combined mortality/dialysis outcome compared with patients with AKI detected by creatinine alone (p=0.002). Limitations There were few adverse clinical outcomes, limiting our ability to detect differences in outcomes between subgroups of patients based upon their definitions of AKI. Conclusion In this large multicenter study, we found that cystatin C was less sensitive for AKI detection compared with creatinine. However, confirmation by cystatin C appeared to identify a subset of
Hussein, Hayder K.; Prabhu, Mahesh; Kanagasundaram, N. Suren
Summary Background and objectives This study measured the association between the Acute Kidney Injury Network (AKIN) diagnostic and staging criteria and surrogates for baseline serum creatinine (SCr) and body weight, compared urine output (UO) with SCr criteria, and assessed the relationships between use of diuretics and calibration between criteria and prediction of outcomes. Design, setting, participants, & measurements This was a retrospective cohort study using prospective measurements of SCr, hourly UO, body weight, and drug administration records from 5701 patients admitted, after cardiac surgery, to a cardiac intensive care unit between 1995 and 2006. Results More patients (n=2424, 42.5%) met SCr diagnostic criteria with calculated SCr assuming a baseline estimated GFR of 75 ml/min per 1.73 m2 than with known baseline SCr (n=1043, 18.3%). Fewer patients (n=484, 8.5%) met UO diagnostic criteria with assumed body weight (70 kg) than with known weight (n=624, 10.9%). Agreement between SCr and UO criteria was fair (κ=0.28; 95% confidence interval 0.25–0.31). UO diagnostic criteria were specific (0.95; 0.94–0.95) but insensitive (0.36; 0.33–0.39) compared with SCr. Intravenous diuretics were associated with higher probability of falling below the UO diagnostic threshold compared with SCr, higher 30-day mortality (relative risk, 2.27; 1.08–4.76), and the need for renal support (4.35; 1.82–10.4) compared with no diuretics. Conclusions Common surrogates for baseline estimated GFR and body weight were associated with misclassification of AKIN stage. UO criteria were insensitive compared with SCr. Intravenous diuretic use further reduced agreement and confounded association between AKIN stage and 30-day mortality or need for renal support. PMID:22246280
Acute Kidney Injury (AKI); Chronic Kidney Disease (CKD); End Stage Renal Disease (ESRD); Estimated Glomerular Filtration Rate (eGFR); Neutrophil Gelatinase-associated Lipocalin (NGAL); Serum Creatinine (SCr); Urine Creatinine (UCr); Urine Albumin (UAlb)
Sandu, AM; Popescu, M; Iacobini, MA; Stoian, R; Neascu, C; Popa, F
The aim of this article is to analyze cardiac dysfunctions occurring after spinal cord injury (SCI). Cardiac dysfunctions are common complications following SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. We reviewed epidemiology of cardiac disturbances after SCI, and neuroanatomy and pathophysiology of autonomic nervous system, sympathetic and parasympathetic. SCI causes disruption of descendent pathways from central control centers to spinal sympathetic neurons, originating into intermediolateral nuclei of T1–L2 spinal cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant cardiac dysfunction. Impairment of autonomic nervous control system, mostly in patients with cervical or high thoracic SCI, causes cardiac dysrrhythmias, especially bradycardia and, rarely, cardiac arrest, or tachyarrhytmias and hypotension. Specific complication dependent on the period of time after trauma like spinal shock and autonomic dysreflexia are also reviewed. Spinal shock occurs during the acute phase following SCI and is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe bradycardia and hypotension. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life–threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5–T6). Besides all this, additional cardiac complications, such as cardiac deconditioning and coronary heart disease may also occur. Proper prophylaxis, including nonpharmacologic and pharmacological strategies and cardiac rehabilitation diminish occurrence of the cardiac dysfunction following
Kim, Eunhee; Park, Jung Bo; Kim, Youngwon; Yang, Ji-Hyuk; Jun, Tae-Gook; Kim, Chung Su
Acute kidney injury (AKI) after pediatric cardiac surgery is associated with high morbidity and mortality. Modifiable risk factors for postoperative AKI including perioperative anesthesia-related parameters were assessed. The authors conducted a single-center, retrospective cohort study of 220 patients (aged 10 days to 19 years) who underwent congenital cardiac surgery between January and December 2012. The incidence of AKI within 7 days postoperatively was determined using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Ninety-two patients (41.8%) developed AKI and 18 (8.2%) required renal replacement therapy within the first postoperative week. Among patients who developed AKI, 57 patients (25.9%) were KDIGO stage 1, 27 patients (12.3%) were KDIGO stage 2, and eight patients (3.6%) were KDIGO stage 3. RACHS-1 (Risk-Adjusted classification for Congenital Heart Surgery) category, perioperative transfusion and fluid administration as well as fluid overload were compared between patients with and without AKI. Multivariable logistic regression analyses determined the risk factors for AKI. AKI was associated with longer hospital stay or ICU stay, and frequent sternal wound infections. Younger age (<12 months) [odds ratio (OR), 4.01; 95% confidence interval (CI), 1.77–9.06], longer cardiopulmonary bypass (CPB) time (OR, 2.45; 95% CI, 1.24–4.84), and low preoperative hemoglobin (OR, 2.40; 95% CI, 1.07–5.40) were independent risk factors for AKI. Fluid overload was not a significant predictor for AKI. When a variable of hemoglobin concentration increase (>3 g/dl) from preoperative level on POD1 was entered into the multivariable analysis, it was independently associated with postoperative AKI (OR, 6.51; 95% CI, 2.23–19.03 compared with no increase). This association was significant after adjustment with patient demographics, medication history and RACHS-1 category (hemoglobin increase >3g/dl vs. no increase: adjusted OR, 6.94; 95% CI, 2.33–20
Brown, Jeremiah R.; Parikh, Chirag R.; Ross, Cathy S.; Kramer, Robert S.; Magnus, Patrick C.; Chaisson, Kristine; Boss, Richard A.; Helm, Robert E.; Horton, Susan R.; Hofmaster, Patricia; Desaulniers, Helen; Blajda, Pamela; Westbrook, Benjamin M.; Duquette, Dennis; LeBlond, Kelly; Quinn, Reed D.; Jones, Cheryl; DiScipio, Anthony W.; Malenka, David J.
Background Of patients undergoing cardiac surgery in the United States, 15–20% are re-hospitalized within 30-days. Current models to predict readmission have not evaluated the association between severity of post-operative acute kidney injury (AKI) and 30-day readmissions. Methods We collected data from 2,209 consecutive patients who underwent either coronary artery bypass (CABG) or valve surgery at seven member hospitals of the Northern New England Cardiovascular Disease Study Group Cardiac Surgery Registry (NNE) between July 2008 and December 2010. Administrative data at each hospital was searched to identify all patients readmitted to the index hospital within 30 days of discharge. We defined AKI Stages by the AKI Network definition of 0.3 or 50% increase (Stage 1), 2-fold increase (stage 2) and a 3-fold or 0.5 increase if the baseline serum creatinine was at least 4.0 (mg/dL) or new dialysis (stage 3). We evaluate the association between stages of AKI and 30-day readmission using multivariate logistic regression. Results There were 260 patients readmitted within 30-days (12.1%). The median time to readmission was 9 (IQR 4–16) days. Patients not developing AKI following cardiac surgery had a 30-day readmission rate of 9.3% compared to patients developing AKI stage 1 (16.1%), AKI stage 2 (21.8%) and AKI stage 3 (28.6%, p <0.001). Adjusted odds ratios for AKI stage 1 (1.81; 1.35, 2.44), stage 2 (2.39; 1.38, 4.14) and stage 3 (3.47; 1.85–6.50). Models to predict readmission were significantly improved with the addition of AKI stage (c-statistic 0.65, p = 0.001) and net reclassification rate of 14.6% (95%CI: 5.05% to 24.14%, p = .003). Conclusions In addition to more traditional patient characteristics, the severity of post-operative AKI should be used when assessing a patient’s risk for readmission. PMID:24119985
Lewicki, Michelle; Ng, Irene; Schneider, Antoine G
Acute kidney injury (AKI) is common in patients undergoing cardiac surgery among whom it is associated with poor outcomes, prolonged hospital stays and increased mortality. Statin drugs can produce more than one effect independent of their lipid lowering effect, and may improve kidney injury through inhibition of postoperative inflammatory responses. This review aimed to look at the evidence supporting the benefits of perioperative statins for AKI prevention in hospitalised adults after surgery who require cardiac bypass. The main objectives were to 1) determine whether use of statins was associated with preventing AKI development; 2) determine whether use of statins was associated with reductions in in-hospital mortality; 3) determine whether use of statins was associated with reduced need for RRT; and 4) determine any adverse effects associated with the use of statins. We searched the Cochrane Renal Group's Specialised Register to 13 January 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Randomised controlled trials (RCTs) that compared administration of statin therapy with placebo or standard clinical care in adult patients undergoing surgery requiring cardiopulmonary bypass and reporting AKI, serum creatinine (SCr) or need for renal replacement therapy (RRT) as an outcome were eligible for inclusion. All forms and dosages of statins in conjunction with any duration of pre-operative therapy were considered for inclusion in this review. All authors extracted data independently and assessments were cross-checked by a second author. Likewise, assessment of study risk of bias was initially conducted by one author and then by a second author to ensure accuracy. Disagreements were arbitrated among authors until consensus was reached. Authors from two of the included studies provided additional data surrounding post-operative SCr as well as need for RRT. Meta-analyses were used to assess the outcomes of AKI, SCr
Mikłaszewska, Monika; Korohoda, Przemysław; Zachwieja, Katarzyna; Mroczek, Tomasz; Drożdż, Dorota; Sztefko, Krystyna; Moczulska, Anna; Pietrzyk, Jacek A
Cardiosurgical operations in cardiopulmonary bypass (CPB) constitute a risk of acute kidney injury (AKI). The aim of the study was an assessment of AKI risk in children within the first 24 hours after CPB cardiac surgery, evaluating serum interleukin 6 (sIL6). The study included 47 children with congenital heart disease operated in CPB. Blood samples were taken before the procedure (0 hour) as well as at 2, 6, 12, 18 and 24 hours after the operation. AKI was confirmed in 19 children. The mean sIL6 concentration in the AKI compared with non-AKI group was: 180.6 vs. 93.7; p = 0.0017. The maximum sIL6 in the AKI group was obtained at 2 hrs after CPB (350.36 pg/ml). Logistic regression analysis for AKI development depending on the value of sIL6 at 2 hrs after CPB proved that every rise of sIL6 by 100 pg/ml increased the chance of AKI development by 70% (p = 0.0161). With every circulatory arrest time prolongation by 10 minutes for a given sIL6 concentration, the chance of AKI development increased by 47% (p = 0.0407). AKI risk at 2 hrs after CPB, for a sIL6 cut-off point amounting to 185 pg/ml, increased more than 3-fold (AUROC - 68%). Determining sIL6 in children after cardiosurgical operations at 2 hrs after the procedure constitutes a good, yet not a perfect marker of AKI risk development. Nomograms of the constant risk values of AKI were worked out presenting the ranges of values in relation to serum IL6 concentrations and the child's body mass, age and the time of circulatory arrest.
Li, Xue-feng; Wang, Xian
Cardiac injury is the most serious adverse event in acupuncture therapy. The causes include needling chest points near the heart, the cardiac enlargement and pericardial effusion that will enlarge the projected area on the body surface and make the proper depth of needling shorter, and the incorrect needling method of the points. Therefore, acupuncture practitioners must be familiar with the points of the heart projected area on the chest and the correct needling methods in order to reduce the risk of acupuncture therapy related cardiac injury.
Van Hook, James W
Acute kidney injury complicates the care of a relatively small number of pregnant and postpartum women. Several pregnancy-related disorders such as preeclampsia and thrombotic microangiopathies may produce acute kidney injury. Prerenal azotemia is another common cause of acute kidney injury in pregnancy. This manuscript will review pregnancy-associated acute kidney injury from a renal functional perspective. Pathophysiology of acute kidney injury will be reviewed. Specific conditions causing acute kidney injury and treatments will be compared.
Kim, Jun Hyun; Kim, Hyun Jung; Kim, Ji Yeon; Ahn, Hyeong sik; Ahn, Il Min; Choe, Won Joo; Lim, Choon-Hak
The aim of this study was to determine whether or not perioperative administration of sodium bicarbonate had a preventive effect on cardiac surgery-associated acute kidney injury (CSA-AKI) as shown in randomized controlled trials. The authors conducted a systematic review and meta-analysis using MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and KoreaMed. The authors searched MEDLINE, EMBASE, CENTRAL, and KoreaMed without language and date restrictions. They used both MeSH and free-text terms to identify relevant studies. Electronic searches were undertaken on July 31, 2014. Five randomized controlled studies included in this review. There were no differences in the development of CSA-AKI among patients in the sodium bicarbonate group compared with those in the control group (5 trials, 1,092 patients; n = 233 of 547 in sodium bicarbonate (SB) group versus 225 of 545 in control group (SC); risk ratio (RR), 0.95; 95% confidence interval (CI), 0.74-1.22. Also, there were no statistical differences in in-hospital mortality (3 trials, 573 patients; n = 21 of 288 in SB versus 14 of 285 in SC; RR, 1.44; 95% CI, 0.76-2.72), need for renal replacement therapy (4 trials, 1,000 patients; n = 21 of 503 in SB versus 23 of 497 in SC; RR, 0.90; 95% CI, 0.50-1.60), length of stay in the intensive care unit (ICU) (hours) (4 trials, n = 969 patients, weighted men difference (WMD), 2.17; 95% CI, -1.15-5.49), and length of ventilation (hours) (4 trials, 969 patients; WMD, 0.34; 95% CI,-0.80-1.48). Perioperative administration of sodium bicarbonate did not reduce the rate of CSA-AKI in randomized controlled trials. Therefore, use of perioperative administration of sodium bicarbonate for the prevention of CSA-AKI is questionable. Copyright © 2015 Elsevier Inc. All rights reserved.
Cell death due to DNA damage by ionizing radiation causes acute radiation injury of tissues and organs. Frequency and severity of the injuries increase according to dose increase, when the dose becomes more than threshold dose. The threshold dose of acute human radiation death is 1 Gy and LD50 of human is 4 Gy. Human dies due to the cerebrovascular syndrome, the gastrointestinal syndrome or the hematopoetic syndrome, when he received more than 20 Gy, 10-20 Gy or 3-8 Gy to his total body, respectively. Any tissue or organ, including embryo and fetus, does not show the acute injury, when it received less than 100 mSv. Acute injuries are usually reversible, and late injuries are sometimes irreversible.
Boehm, Johannes; Eichhorn, Stefan; Kornek, Matthias; Hauner, Katharina; Prinzing, Anatol; Grammer, Joachim; Lahm, Harald; Wagenpfeil, Stefan; Lange, Ruediger
Acute kidney injury following cardiac surgery depicts a severe clinical problem that is strongly associated with adverse short- and long-term outcome. We analyzed two common genetic polymorphisms that have previously been linked to renal failure and inflammation, and have been supposed to be associated with cardiac surgery associated-acute kidney injury (CSA-AKI). A total of 1415 consecutive patients who underwent elective cardiac surgery with CPB at our institution were prospectively enrolled. Patients were genotyped for Apolipoprotein E (ApoE E2,E3,E4) (rs429358 and rs7412) and TNF-α-308 G > A (rs1800629). Demographic characteristics and procedural data revealed no significant differences between genotypes. No association between ApoE (E2,E3,E4) and TNF-α-308 G > A genotypes and the RIFLE criteria could be detected. Several multiple linear regression analyses for postoperative creatinine increase revealed highly significant associations for aortic cross clamp time (p < 0.001), CPB-time (p < 0.001), norepinephrine (p < 0.001), left ventricular function (p = 0.004) and blood transfusion (p < 0.001). No associations were found for ApoE (E2,E3,E4) and TNF-α-308 G > A genotypes or baseline creatinine. When the sample size is 1415, the multiple linear regression test of R(2 )= 0 for seven covariates assuming normal distribution will have at least 99% power with significance level 0.05 to detect an R(2) of 0.108 or 0.107 as observed in the data. ApoE (E2,E3,E4) polymorphism and the TNF-α-308 G > A polymorphism are not associated with renal injury after CPB.
Porter, J. M.; Shakespeare, P. G.
Cardiac output after burn injury has been measured by the non-invasive method of impedance plethysmography. An initial study of 143 normal subjects was undertaken in order to investigate variations in cardiac output with age. Fifteen patients were monitored during resuscitation after extensive burns. Fourteen patients showed a depression of stroke volume below the lower limits of the normal range, derived from the initial study on normal people. PMID:6691694
Ruthirago, Doungporn; Julayanont, Parunyou; Tantrachoti, Pakpoom; Kim, Jongyeol; Nugent, Kenneth
Cardiac arrhythmias and electrocardiogram (ECG) abnormalities occur frequently but are often underrecognized after strokes. Acute ischemic and hemorrhagic strokes in some particular area of brain can disrupt central autonomic control of the heart, precipitating cardiac arrhythmias, ECG abnormalities, myocardial injury and sometimes sudden death. Identification of high-risk patients after acute stroke is important to arrange appropriate cardiac monitoring and effective management of arrhythmias, and to prevent cardiac morbidity and mortality. More studies are needed to better clarify pathogenesis, localization of areas associated with arrhythmias and practical management of arrhythmias and abnormal ECGs after acute stroke.
Selewski, David T; Charlton, Jennifer R; Jetton, Jennifer G; Guillet, Ronnie; Mhanna, Maroun J; Askenazi, David J; Kent, Alison L
In recent years, there have been significant advancements in our understanding of acute kidney injury (AKI) and its impact on outcomes across medicine. Research based on single-center cohorts suggests that neonatal AKI is very common and associated with poor outcomes. In this state-of-the-art review on neonatal AKI, we highlight the unique aspects of neonatal renal physiology, definition, risk factors, epidemiology, outcomes, evaluation, and management of AKI in neonates. The changes in renal function with gestational and chronologic age are described. We put forth and describe the neonatal modified Kidney Diseases: Improving Global Outcomes AKI criteria and provide the rationale for its use as the standardized definition of neonatal AKI. We discuss risk factors for neonatal AKI and suggest which patient populations may warrant closer surveillance, including neonates <1500 g, infants who experience perinatal asphyxia, near term/ term infants with low Apgar scores, those treated with extracorporeal membrane oxygenation, and those requiring cardiac surgery. We provide recommendations for the evaluation and treatment of these patients, including medications and renal replacement therapies. We discuss the need for long-term follow-up of neonates with AKI to identify those children who will go on to develop chronic kidney disease. This review highlights the deficits in our understanding of neonatal AKI that require further investigation. In an effort to begin to address these needs, the Neonatal Kidney Collaborative was formed in 2014 with the goal of better understanding neonatal AKI, beginning to answer critical questions, and improving outcomes in these vulnerable populations.
Hu, Peng-hua; Chen, Yuan-han; Liang, Xin-ling; Li, Rui-zhao; Li, Zhi-lian; Jiang, Fen; Shi, Wei
To explore the influence of early postoperative use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) or diuretics on acute kidney injury (AKI) after cardiac surgery in elderly patients. Data from elderly patients (age≥60 years old) who underwent cardiac surgery with extracorporeal circulation in Guangdong General Hospital between January 2007 and December 2010 were analyzed in this retrospective research. The primary endpoint was AKI as diagnosed according to the serum creatinine criteria of RIFLE (risk, injury, failure, loss, end stage renal disease). The baseline serum creatinine was defined as the latest serum creatinine level before cardiac surgery. Multivariate analysis by logistic regression was used to obtain the independent risk factors for AKI. Among 618 elderly patients, 76 (12.3%) patients received ACEI/ARB during early postoperative period, 491 (79.4%) patients were given diuretics during early postoperative period, and postoperative AKI occurred in 394 (63.8%) patients. The incidence of AKI was 46.1% in patients who received early postoperative ACEI/ARB, and 66.2% in patients who did not (P<0.001). Patients who received diuretics postoperatively were less likely to suffer from AKI compared with patients who did not (57.0% vs. 89.8%, P<0.001). After adjustment of other potential factors of postoperative AKI, logistic regression analysis showed that early postoperative use of ACEI/ARB [odds ratio (OR)=0.131, 95% confidence interval (95%CI) 0.033-0.517, P=0.004], and early postoperative use of diuretics (OR=0.149, 95%CI 0.076-0.291, P<0.001) independently predicted the occurrence of AKI. Early postoperative use of ACEI/ARB or diuretics is associated with a lower incidence of AKI after cardiac surgery with extracorporeal circulation in elderly patients.
Garrido, Jose M; Candela-Toha, Angel M; Parise-Roux, Diego; Tenorio, Mayte; Abraira, Victor; Del Rey, Jose M; Prada, Beatriz; Ferreiro, Andrea; Liaño, Fernando
Acute kidney injury (AKI) after cardiac surgery is associated with adverse patient outcome. A new definition and staging system for AKI based on creatinine kinetics (CKs) has been proposed recently. Their proponents hypothesize that early absolute increases in serum creatinine (sCr) after kidney injury are superior to percentage increases, especially in patients with chronic kidney disease (CKD). The aims of our study were to measure agreement between CK definition and the current consensus definition [risk, injury, failure, loss and end-stage renal disease (RIFLE) system], and to compare time to diagnosis and prognostic value between both systems. Retrospective cohort study. Agreement on AKI diagnosis by both classifications, time to diagnosis and prognostic value of both systems were compared in cardiac surgeries performed during a 6-year period (2002-2007) in a single centre. We found substantial agreement between both classifications (0.67). More patients were diagnosed with AKI by the CK definition than by RIFLE criteria both globally (28.2 vs 13.9%) and in every category (16.5 vs 8.4% for CK-1 vs RIFLE-R; 8.4 vs 3.6% for CK-2 vs RIFLE-I and 3.2 vs 2.0% for CK-3 vs RIFLE-F). Time to diagnosis was shorter for the CK definition (1.8 vs 2.5 days). Prognostic value in terms of information about in-hospital death and need for renal replacement was comparable between classifications. In cardiac surgery, the CK definition and classification system showed substantial agreement with the current standard, was more sensitive than RIFLE and detected AKI earlier without loss of prognostic information. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Madsen, Nicolas L; Goldstein, Stuart L; Frøslev, Trine; Christiansen, Christian F; Olsen, Morten
Cardiac surgery associated-acute kidney injury (CS-AKI) occurs in 30-50% of patients undergoing surgery for congenital heart disease. Here we determine if CS-AKI is associated with chronic kidney disease (CKD) in patients with congenital heart disease. Using Danish regional population-based registries, our cohort study included patients with congenital heart disease born between 1990-2010 with first cardiac surgery between 2005 and 2010 (under 15 years of age). Utilizing in- and out-patient laboratory serum creatinine data, we identified individuals fulfilling KDIGO stages of AKI within 5 days of cardiac surgery. A unique personal identifier enabled unambiguous data linkage and virtually complete follow-up. The cumulative incidences of CKD stages 2-5 according to presence of CS-AKI were computed utilizing serum creatinine values and Pottel's formula. Using Cox regression, the corresponding hazard ratios were computed, adjusting for sex, age at first cardiac surgery, calendar period of surgery, and congenital heart disease severity. Of 382 patients with congenital heart disease undergoing cardiac surgery, 127 experienced CS-AKI within 5 days of surgery. Median follow-up was 4.9 years. The five-year cumulative incidence of CKD for patients with CS-AKI was 12% (95% confidence interval 7%-20%), significantly higher than the 3% (1%-5%) for those without CS-AKI with a significant adjusted hazard ratio of 3.8 (1.4-10.4). Thus, CS-AKI in patients with congenital heart disease is common and is associated with an increased risk for CKD. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
Kessler, Thorsten; Schunkert, Heribert
Myocardial infarction (MI) is one of the major contributors to worldwide morbidity and mortality. It is atherosclerosis’ most dreadful complication and occurs after the supply of oxygenated blood to the heart is blocked. Understanding how cardiac tissue is injured and later regenerates is of crucial importance to improve the sequelae after the acute event. We now understand that the immune system substantially contributes to both the acute inflammatory response and the regenerative response that follow tissue injury after MI. In this review, we will focus on the role of monocytes and macrophages, which are cellular protagonists of the immune system, in acute cardiac injury and post-MI repair. PMID:28446966
Sager, Hendrik B; Kessler, Thorsten; Schunkert, Heribert
Myocardial infarction (MI) is one of the major contributors to worldwide morbidity and mortality. It is atherosclerosis' most dreadful complication and occurs after the supply of oxygenated blood to the heart is blocked. Understanding how cardiac tissue is injured and later regenerates is of crucial importance to improve the sequelae after the acute event. We now understand that the immune system substantially contributes to both the acute inflammatory response and the regenerative response that follow tissue injury after MI. In this review, we will focus on the role of monocytes and macrophages, which are cellular protagonists of the immune system, in acute cardiac injury and post-MI repair.
Wu, Buyun; Ma, Lulu; Shao, Yongfeng; Liu, Si; Yu, Xiangbao; Zhu, Yamei; Xu, Xianrong; Xing, Changying; Mao, Huijuan
To evaluate the long-term outcomes of Chinese patients with cardiac surgery-associated acute kidney injury (CSA-AKI). Patients who underwent cardiac surgery with a median 3-year follow-up were enrolled. The long-term survival rate and the incidence of chronic kidney disease (CKD) were recorded, and related risk factors were analyzed. Of all 1,363 patients, 457 (33.5%) developed CSA-AKI. The AKI patients had a lower 3-year survival rate (88.8 vs. 97.2%, respectively, p < 0.001) and a higher incidence of CKD stages 3-5 (9.9 vs. 2.3%, respectively, p < 0.001) than the non-AKI patients. Cox regression analysis showed that AKI, atrial fibrillation, chronic cardiac insufficiency, longer surgical duration, respiratory failure after surgery, and longer mechanical ventilation time were associated with long-term mortality, while AKI, older age, and lower baseline kidney function were associated with incident CKD stages 3-5. CSA-AKI increased the risk of 3-year mortality and incident CKD stages 3-5. © 2017 S. Karger AG, Basel.
Lopez-Delgado, Juan C; Esteve, Francisco; Torrado, Herminia; Rodríguez-Castro, David; Carrio, Maria L; Farrero, Elisabet; Javierre, Casimiro; Ventura, Josep L; Manez, Rafael
The development of acute kidney injury (AKI) is associated with poor outcome. The modified RIFLE (risk, injury, failure, loss of kidney function, and end-stage renal failure) classification for AKI, which classifies patients with renal replacement therapy needs according to RIFLE failure class, improves the predictive value of AKI in patients undergoing cardiac surgery. Our aim was to assess risk factors for post-operative AKI and the impact of renal function on short- and long-term survival among all AKI subgroups using the modified RIFLE classification. We prospectively studied 2,940 consecutive cardiosurgical patients between January 2004 and July 2009. AKI was defined according to the modified RIFLE system. Pre-operative, operative and post-operative variables usually measured on and during admission, which included main outcomes, were recorded together with cardiac surgery scores and ICU scores. These data were evaluated for association with AKI and staging in the different RIFLE groups by means of multivariable analyses. Survival was analyzed via Kaplan-Meier and a risk-adjusted Cox proportional hazards regression model. A complete follow-up (mean 6.9 ± 4.3 years) was performed in 2,840 patients up to April 2013. Of those patients studied, 14% (n = 409) were diagnosed with AKI. We identified one intra-operative (higher cardiopulmonary bypass time) and two post-operative (a longer need for vasoactive drugs and higher arterial lactate 24 hours after admission) predictors of AKI. The worst outcomes, including in-hospital mortality, were associated with the worst RIFLE class. Kaplan-Meier analysis showed survival of 74.9% in the RIFLE risk group, 42.9% in the RIFLE injury group and 22.3% in the RIFLE failure group (P <0.001). Classification at RIFLE injury (Hazard ratio (HR) = 2.347, 95% confidence interval (CI) 1.122 to 4.907, P = 0.023) and RIFLE failure (HR = 3.093, 95% CI 1.460 to 6.550, P = 0.003) were independent predictors for
Introduction The development of acute kidney injury (AKI) is associated with poor outcome. The modified RIFLE (risk, injury, failure, loss of kidney function, and end-stage renal failure) classification for AKI, which classifies patients with renal replacement therapy needs according to RIFLE failure class, improves the predictive value of AKI in patients undergoing cardiac surgery. Our aim was to assess risk factors for post-operative AKI and the impact of renal function on short- and long-term survival among all AKI subgroups using the modified RIFLE classification. Methods We prospectively studied 2,940 consecutive cardiosurgical patients between January 2004 and July 2009. AKI was defined according to the modified RIFLE system. Pre-operative, operative and post-operative variables usually measured on and during admission, which included main outcomes, were recorded together with cardiac surgery scores and ICU scores. These data were evaluated for association with AKI and staging in the different RIFLE groups by means of multivariable analyses. Survival was analyzed via Kaplan-Meier and a risk-adjusted Cox proportional hazards regression model. A complete follow-up (mean 6.9 ± 4.3 years) was performed in 2,840 patients up to April 2013. Results Of those patients studied, 14% (n = 409) were diagnosed with AKI. We identified one intra-operative (higher cardiopulmonary bypass time) and two post-operative (a longer need for vasoactive drugs and higher arterial lactate 24 hours after admission) predictors of AKI. The worst outcomes, including in-hospital mortality, were associated with the worst RIFLE class. Kaplan-Meier analysis showed survival of 74.9% in the RIFLE risk group, 42.9% in the RIFLE injury group and 22.3% in the RIFLE failure group (P <0.001). Classification at RIFLE injury (Hazard ratio (HR) = 2.347, 95% confidence interval (CI) 1.122 to 4.907, P = 0.023) and RIFLE failure (HR = 3.093, 95% CI 1.460 to 6.550, P = 0.003) were
Huang, Chunyan; Gu, Hongmei; Zhang, Wenjun; Manukyan, Mariuxi C.; Shou, Weinian
Stromal cell-derived factor-1α (SDF-1) has been reported to mediate cardioprotection through the mobilization of stem cells into injured tissue and an increase in local angiogenesis after myocardial infarction. However, little is known regarding whether SDF-1 induces acute protection following global myocardial ischemia/reperfusion (I/R) injury and if so, by what molecular mechanism. SDF-1 binding to its cognate receptor CXCR4 has been shown to activate STAT3 in a variety of cells. STAT3 is a cardioprotective factor and may mediate SDF-1/CXCR4-induced acute protection. We hypothesized that SDF-1 would improve myocardial function through CXCR4-increased STAT3 activation following acute I/R. Isolated mouse hearts were subjected to 25-min global ischemia/40-min reperfusion and divided into groups of 1) vehicle; 2) SDF-1; 3) AMD3100, a CXCR4 inhibitor; 4) SDF-1 + AMD3100; 5) Stattic, a STAT3 inhibitor; 6) SDF-1 + Stattic; 7) cardiomyocyte-restricted ablation of STAT3 (STAT3KO); 8) STAT3KO + SDF-1; 9) Ly294002, an inhibitor of the Akt pathway; and 10) SDF-1 + Ly294002. Reagents were infused into hearts within 5 min before ischemia. SDF-1 administration significantly improved postischemic myocardial functional recovery in a dose-dependent manner. Additionally, pretreatment with SDF-1 reduced cardiac apoptotic signaling and increased myocardial STAT3 activation following acute I/R. Inhibition of the SDF-1 receptor CXCR4 neutralized these protective effects by SDF-1 in hearts subjected to I/R. Notably, inhibition of the STAT3 pathway or use of STAT3KO hearts abolished SDF-1-induced acute protection following myocardial I/R. Our results represent the first evidence that the SDF-1/CXCR4 axis upregualtes myocardial STAT3 activation and, thereby, mediates acute cardioprotection in response to global I/R. PMID:21821779
Li, Bingjue; Lang, Xiabing; Cao, Luxi; Wang, Yuchen; Lu, Yingying; Feng, Shi; Yang, Yi; Chen, Jianghua; Jiang, Hong
It is currently controversial whether remote ischemic preconditioning (RIPC) reduces the incidence of acute kidney injury (AKI) in patients undergoing cardiovascular interventions. The main objective of this meta-analysis was to investigate whether RIPC provides renal protection for patients undergoing cardiac or vascular surgery. We searched the PubMed database (1966-Oct 2015), Embase database (1966-Oct 2015), Google Scholar, Cochrane Library, ClinicalTrials Database and Open Grey. Then we conducted a meta-analysis of the randomized controlled trials that met the inclusion criteria of our study. The interventions included use of an inflatable tourniquet around the limbs or cross-clamping of the iliac arteries before surgery (RIPC groups) and general cardiovascular intervention (control groups). The main outcomes examined included the incidence of AKI; changes in acute kidney injury biomarkers; and use of renal replacement therapy. Other outcomes examined included in-hospital mortality and the lengths of hospital stay and intensive care unit (ICU) stay. Finally, we screened 26 eligible studies containing 6699 patients who underwent cardiac or vascular interventions with RIPC (n = 3343) or without RIPC (n = 3356). The AKI incidence was decreased in the RIPC group as was the length of ICU stay. There were no differences in the changes in AKI biomarkers, use of renal replacement therapy or in-hospital mortality between the two groups. Remote ischemic preconditioning may decrease the occurrence of AKI in cardiovascular surgery patients. Since studies included have a significant heterogeneity, meta-analyses using a stricter inclusion criteria are needed to clarify the renoprotection effect of RIPC.
Hansen, Malene Kærslund; Gammelager, Henrik; Mikkelsen, Martin Majlund; Hjortdal, Vibeke Elisabeth; Layton, J Bradley; Johnsen, Søren Paaske; Christiansen, Christian Fynbo
The prognostic impact of acute kidney injury (AKI) on long-term clinical outcomes remains controversial. We examined the five-year risk of death, myocardial infarction, and stroke after elective cardiac surgery complicated by AKI. We conducted a cohort study among adult elective cardiac surgical patients without severe chronic kidney disease and/or previous heart or renal transplant surgery using data from population-based registries. AKI was defined by the Acute Kidney Injury Network (AKIN) criteria as a 50% increase in serum creatinine from baseline level, acute creatinine rise of ≥26.5 μmol/L (0.3 mg/dL) within 48 hours, and/or initiation of renal replacement therapy within five days after surgery. We followed patients from the fifth post-operative day until myocardial infarction, stroke or death within five years. Five-year risk was computed by the cumulative incidence method and compared with hazards ratios (HR) from a Cox proportional hazards regression model adjusting for propensity score. A total of 287 (27.9%) of 1,030 patients developed AKI. Five-year risk of death was 26.5% (95% CI: 21.2 to 32.0) among patients with AKI and 12.1% (95% CI: 10.0 to 14.7) among patients without AKI. The corresponding adjusted HR of death was 1.6 (95% CI: 1.1 to 2.2). Five-year risk of myocardial infarction was 5.0% (95% CI: 2.9 to 8.1) among patients with AKI and 3.3% (95% CI: 2.1 to 4.8) among patients without AKI. Five-year risk of stroke was 5.0% (95% CI: 2.8 to 7.9) among patients with AKI and 4.2% (95% CI: 2.9 to 5.8) among patients without AKI. Adjusted HRs were 1.5 (95% CI: 0.7 to 3.2) of myocardial infarction and 0.9 (95% CI: 0.5 to 1.8) of stroke. AKI, within five days after elective cardiac surgery, was associated with increased five-year mortality and a statistically insignificant increased risk of myocardial infarction. No association was seen with the risk of stroke.
Ximenes, Rafael O.; Farias, Alberto Q.; Helou, Claudia M.B.
Background Hemodynamic abnormalities and acute kidney injury (AKI) are often present in infected cirrhotic patients. Hence, an early diagnosis of AKI is necessary, which might require the validation of new predictors as the determinations of urinary neutrophil gelatinase-associated lipocalin (uNGAL) and cardiac output. Methods We evaluated 18 infected cirrhotic patients subdivided into two groups at admission (0 hours). In Group I, we collected urine samples at 0 hours, 6 hours, 24 hours, and 48 hours for uNGAL and fractional excretion of sodium determinations. In Group II, we measured cardiac output using echocardiography. Results The age of patients was 55.0±1.9 years, and 11 patients were males. The Model for End-Stage Liver Disease score was 21±1, whereas the Child–Pugh score was C in 11 patients and B in 7 patients. Both patients in Group I and Group II showed similar baseline characteristics. In Group I, we diagnosed AKI in 5 of 9 patients, and the mean time to this diagnosis by measuring serum creatinine was 5.4 days. Patients with AKI showed higher uNGAL levels than those without AKI from 6 hours to 48 hours. The best accuracy using the cutoff values of 68 ng uNGAL/mg creatinine was achieved at 48 hours when we distinguished patients with and without AKI in all cases. In Group II, we diagnosed AKI in 4 of 9 patients, and cardiac output was significantly higher in patients who developed AKI at 0 hours. Conclusion Both uNGAL and cardiac output determinations allow the prediction of AKI in infected cirrhotic patients earlier than increments in serum creatinine. PMID:26484038
Ricci, Zaccaria; Di Nardo, Matteo; Iacoella, Claudia; Netto, Roberta; Picca, Stefano; Cogo, Paola
This study evaluated the performance of the pediatric RIFLE (pRIFLE) score for acute kidney injury (AKI) diagnosis and prognosis after pediatric cardiac surgery. It was a single-center prospective observational study developed in a pediatric cardiac intensive care unit (pCICU) of a tertiary children's hospital. The study enrolled 160 consecutive children younger than 1 year with congenital heart diseases and undergoing cardiac surgery with cardiopulmonary bypass. Of the 160 children, 50 (31 %) were neonates, and 20 (12 %) had a univentricular heart. Palliative surgery was performed for 53 patients (33 %). A diagnosis of AKI was determined for 90 patients (56 %), and 68 (42 %) of these patients achieved an "R" level of AKI severity, 17 patients (10 %) an "I" level, and 5 patients (3 %) an "F" level. Longer cross-clamp times (p = 0.045), a higher inotropic score (p = 0.02), and a higher Risk-Adjusted Classification for Congenital Heart Surgery score (p = 0.048) but not age (p = 0.27) correlated significantly with pRIFLE class severity. Patients classified with a higher pRIFLE score required a greater number of mechanical ventilation days (p = 0.03) and a longer pCICU stay (p = 0.045). Renal replacement therapy (RRT) was needed for 13 patients (8.1 %), with two patients receiving continuous hemofiltration, and 11 patients receiving peritoneal dialysis. At the start of dialysis, the distribution of RRT patients differed significantly within pRIFLE classes (p = 0.015). All deceased patients were classified as pRIFLE "I" or "F" (p = 0.0001). The findings showed that pRIFLE is easily and feasibly applied for pediatric patients with congenital heart disease. The pRIFLE classification showed that AKI incidence in pediatric cardiac surgery infants is high and associated with poorer outcomes.
Brix, Silke; Stahl, Rolf
Acute kidney injury (AKI) is an important part of renal diseases and a common clinical problem. AKI is an acute decline in renal function. Due to a lack of therapeutic options, prevention and optimal management of patients with AKI are the most important strategies. Although seldom the sole cause of patients' death, AKI is associated with a significant increase in mortality. Our objective is to draw the attention towards the prevention of AKI of non-renal causes.
Karim, Habib Md Reazaul; Yunus, Mohd; Saikia, Manuj Kumar; Kalita, Jyoti Prasad; Mandal, Mrinal
Introduction: Cardiac surgery-associated kidney injury (CSA-AKI) is common but relatively less is known about its progression. The present study is aimed at evaluating the incidence and course of CSA-AKI and its relationship with the different durations of cardiopulmonary bypass (CPB) and cross clamp times. Materials and Methods: Occurrences of CSA-AKI are evaluated as per the Akin Kidney Injury Network (AKIN) criteria over the course of 5 postoperative day (POD) in 100 patients. The relationship of different durations of CPB and aortic cross clamp time with CSA-AKI is analyzed by Chi-squared test for trend and other appropriate tests using INSTAT software. Results: One hundred (43 male, 57 female; mean age of 37.01 ± 12.28 years, and baseline mean serum creatinine 0.99 ± 0.20 mg %) patients undergone mostly valve replacement, and congenital heart disease correction was evaluated. Nearly 49% suffered CSA-AKI (81.63% AKIN Class I) with maximum numbers on 2nd POD. Serum creatinine followed a falling trend 3rd POD onward except in 8.16% cases of CSA-AKI. Oliguria was absent even in AKIN Class II. The CPB time >70 min and cross clamp time >60 min increase CSA-AKI risk by an OR of 4.76 and 2.84, respectively (P < 0.05). Conclusion: CSA-AKI is very prevalent; mostly of AKIN Class I and increases with increasing CPB and cross clamp time. Urine output is not a reliable indicator of CSA-AKI. The AKIN Class II on the very 1st POD or increasing trend of serum creatinine beyond 3rd POD should alert for early intervention. PMID:28074790
Kujala, U M; Nylund, T; Taimela, S
The aim of this study was to characterize the type and severeity of acute injuries occurring in Finnish orienteerers in 1987 to 1991. The study is based on the orienteering license insurance records accounting for 2189 orienteering injuries during 69268 person-years of exposure in active orienteerers. Of these orienteerers, 73.0% were male; 73.5% (N = 1608) of all injuries occurred in males, so the injury rate was similar in males and females. The rate was highest in orienteerers 20 to 24 years of age and lowest in children. Injuries occurred most commonly during May to September (78.9% or all injuries), the months which include the orienteering competition season, and were more common during competitions (59.8%) than during training. A high number of the injuries occurred during weekends (58.9% of injuries) including 68.1% of all competition injuries and 44.9% of all training injuries. The lower limbs were involved in 1611 (73.6%) of cases, the ankle (28.7%) and the knee (23.2%) being the two most common injury locations. Sprains, strains and contusions were the most common injuries. Wounds were proportionally more common in males than in females while ankle sprains were more common in females. Fractures, seven open and 94 closed, accounted for 4.6% of injuries; they were most common in the hand/wrist/forearm (N = 44) and ankle (N = 16), and were more frequent during competition (62.3%) than during training. The most important areas for preventive measures seem to be the ankle and the knee.
Echevarría, J R; San Román, A
Cardiac injuries caused by a heart traumatism are not frequent but, of great importance given their high morbidity. Two different groups in terms of etiology, clinical picture, application of diagnostic techniques, treatment and prognosis can be considered. On one hand, there are cardiac injuries caused by a thoracal contusion, which provokes a contused lesion can affect the free wall, the interventricular septum, the valves, the subvalvular apparatus, the conduction system and the coronary vessels and, on the other hand, cardiac injuries caused by penetrating objects. Cardiac injury can lead to a life-threatening hemodynamic instability which mandates prompt and clear diagnostic and therapeutic approaches.
Introduction Cardiac surgery is frequently needed in patients with infective endocarditis (IE). Acute kidney injury (AKI) often complicates IE and is associated with poor outcomes. The purpose of the study was to determine the risk factors for post-operative AKI in patients operated on for IE. Methods A retrospective, non-interventional study of prospectively collected data (2000–2010) included patients with IE and cardiac surgery with cardio-pulmonary bypass. The primary outcome was post-operative AKI, defined as the development of AKI or progression of AKI based on the acute kidney injury network (AKIN) definition. We used ensemble machine learning (“Super Learning”) to develop a predictor of AKI based on potential risk factors, and evaluated its performance using V-fold cross validation. We identified clinically important predictors among a set of risk factors using Targeted Maximum Likelihood Estimation. Results 202 patients were included, of which 120 (59%) experienced a post-operative AKI. 65 (32.2%) patients presented an AKI before surgery while 91 (45%) presented a progression of AKI in the post-operative period. 20 patients (9.9%) required a renal replacement therapy during the post-operative ICU stay and 30 (14.8%) died during their hospital stay. The following variables were found to be significantly associated with renal function impairment, after adjustment for other risk factors: multiple surgery (OR: 4.16, 95% CI: 2.98-5.80, p<0.001), pre-operative anemia (OR: 1.89, 95% CI: 1.34-2.66, p<0.001), transfusion requirement during surgery (OR: 2.38, 95% CI: 1.55-3.63, p<0.001), and the use of vancomycin (OR: 2.63, 95% CI: 2.07-3.34, p<0.001), aminoglycosides (OR: 1.44, 95% CI: 1.13-1.83, p=0.004) or contrast iodine (OR: 1.70, 95% CI: 1.37-2.12, p<0.001). Post-operative but not pre-operative AKI was associated with hospital mortality. Conclusions Post-operative AKI following cardiopulmonary bypass for IE results from additive hits to the kidney. We
Clark, Audra; Neyra, Javier A; Madni, Tarik; Imran, Jonathan; Phelan, Herb; Arnoldo, Brett; Wolf, Steven E
Acute kidney injury (AKI) is a common and morbid complication after severe burn, with an incidence and mortality as high as 30% and 80%, respectively. AKI is a broad clinical condition with many etiologies, which makes definition and diagnosis challenging. The most recent Kidney Disease: Improving Global Outcomes (KDIGO) consensus guidelines defined stage and severity of AKI based on changes of serum creatinine and urine output (UOP) across time. Burn-related kidney injury is typically classified as early (0-3days after injury) or late (4-14days after injury). Early burn AKI is typically due to hypovolemia, poor renal perfusion, direct cardiac suppression from TNF-alpha, and precipitation of denatured proteins, while late AKI is often due to sepsis, multi-organ failure, and nephrotoxic drugs. Diagnosis can be difficult as UOP and biochemical markers can be relatively normal even with significant renal injury. A sensitive and specific biomarker for the early diagnosis of AKI is sorely needed, and multiple potential biomarkers are being investigated. For treatment, the reversal of the underlying cause is the first intervention. The advent of renal replacement therapy has significantly improved the mortality of burn patients with AKI and should be initiated early if injury progresses despite initial maneuvers. Unfortunately, no beneficial pharmacologic agents have been identified, despite multiple investigations. Of burn patients who survive AKI, the vast majority do not receive long-term hemodialysis and they are generally thought to have a good renal prognosis although this view is shifting. Preliminary data in the burn population suggest that AKI may confer an increased risk of end-stage renal disease and long-term all-cause mortality, but further research is needed. Published by Elsevier Ltd.
Acute kidney injury (AKI) in cardiac surgery is associated with complications, early and late mortality and increased health care expenditures. The overall dynamic comorbidity-adjusted contributions of an episode of AKI on mortality during long-term follow-up have not been fully explored. A longitudinal cohort of 7075 adult patients admitted for cardiac surgery were enrolled in the study. Follow-up data were obtained through telephonic survey after 1, 5, 10, and 15 years or from the National Mortality Registry. All-cause mortality was assessed at five time intervals: I) 30 days after surgery to 1 year; II) 1 to 3 years; III) 3 to 5 years; IV) 5 to 10 years; and V) 10 to 15 years. For the adjustment of mortality for comorbidity and pre-, intra- and postoperative variables, Cox proportional hazard regression models were conducted within each period. The overall incidence of AKI was 36.1%. AKI was an independent predictor of death only during the first five years after surgery (30 days to 1 year: HR 1.834, 95% CI 1.459 to 2.306; 1 to 3 years: HR 1.285, 95% CI 1.023 to 1.610; and 3 to five years: HR 1.330, 95% CI 1.123 to 1.750). Only age, diabetes mellitus and CHF were associated with increased risk of death over the entire follow-up period. Our study demonstrates a transient association of AKI with long-term mortality that progressively decreases and vanishes five years after surgery. The knowledge of this dynamic is crucial to understanding this complex association, planning health care and allocating resources. PMID:28700753
Zappitelli, Michael; Greenberg, Jason H; Coca, Steven G; Krawczeski, Catherine D; Li, Simon; Thiessen-Philbrook, Heather R; Bennett, Michael R; Devarajan, Prasad; Parikh, Chirag R
Research has identified improved biomarkers of acute kidney injury (AKI). Cystatin C (CysC) is a better glomerular filtration rate marker than serum creatinine (SCr) and may improve AKI definition. To determine if defining clinical AKI by increases in CysC vs SCr alters associations with biomarkers and clinical outcomes. Three-center prospective cohort study of intensive care units in New Haven, Connecticut, Cincinnati, Ohio, and Montreal, Quebec, Canada. Participants were 287 patients 18 years or younger without preoperative AKI or end-stage renal disease who were undergoing cardiac surgery. The study dates were July 1, 2007, through December 31, 2009. For biomarker vs clinical AKI associations, the exposures were first postoperative (0-6 hours after surgery) urine interleukin 18, neutrophil gelatinase-associated lipocalin, kidney injury molecule 1, and liver fatty acid-binding protein. For clinical AKI outcome associations, the exposure was Kidney Disease: Improving Global Outcomes AKI definition (based on SCr or CysC). Clinical AKI, length of stay, and length of mechanical ventilation. We determined areas under the receiver operating characteristic curve and odds ratios for first postoperative biomarkers to predict AKI. The SCr-defined vs CysC-defined AKI incidence differed substantially (43.6% vs 20.6%). Percentage agreement was 71% (κ = 0.38); stage 2 or worse AKI percentage agreement was 95%. Interleukin 18 and kidney injury molecule 1 discriminated for CysC-defined AKI better than for SCr-defined AKI. For interleukin 18 and kidney injury molecule 1, the areas under the receiver operating characteristic curve were 0.74 and 0.65, respectively, for CysC-defined AKI, and 0.66 and 0.58, respectively, for SCr-defined AKI. Fifth (vs first) quintile concentrations of both biomarkers were more strongly associated with CysC-defined AKI. For interleukin 18 and kidney injury molecule 1, the odds ratios were 16.19 (95% CI, 3.55-73.93) and 6.93 (95% CI, 1
Zappitelli, Michael; Greenberg, Jason H.; Coca, Steven G.; Krawczeski, Catherine D.; Li, Simon; Thiessen-Philbrook, Heather R.; Bennett, Michael R.; Devarajan, Prasad; Parikh, Chirag R.
IMPORTANCE Research has identified improved biomarkers of acute kidney injury (AKI). Cystatin C (CysC) is a better glomerular filtration rate marker than serum creatinine (SCr) and may improve AKI definition. OBJECTIVE To determine if defining clinical AKI by increases in CysC vs SCr alters associations with biomarkers and clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS Three-center prospective cohort study of intensive care units in New Haven, Connecticut, Cincinnati, Ohio, and Montreal, Quebec, Canada. Participants were 287 patients 18 years or younger without preoperative AKI or end-stage renal disease who were undergoing cardiac surgery. The study dates were July 1, 2007, through December 31, 2009. EXPOSURES For biomarker vs clinical AKI associations, the exposures were first postoperative (0–6 hours after surgery) urine interleukin 18, neutrophil gelatinase – associated lipocalin, kidney injury molecule 1, and liver fatty acid–binding protein. For clinical AKI outcome associations, the exposure was Kidney Disease: Improving Global Outcomes AKI definition (based on SCr or CysC). MAIN OUTCOMES AND MEASURES Clinical AKI, length of stay, and length of mechanical ventilation. We determined areas under the receiver operating characteristic curve and odds ratios for first postoperative biomarkers to predict AKI. RESULTS The SCr-defined vs CysC-defined AKI incidence differed substantially (43.6% vs 20.6%). Percentage agreement was 71% (κ = 0.38); stage 2 or worse AKI percentage agreement was 95%. Interleukin 18 and kidney injury molecule 1 discriminated for CysC-defined AKI better than for SCr-defined AKI. For interleukin 18 and kidney injury molecule 1, the areas under the receiver operating characteristic curve were 0.74 and 0.65, respectively, for CysC-defined AKI, and 0.66 and 0.58, respectively, for SCr-defined AKI. Fifth (vs first) quintile concentrations of both biomarkers were more strongly associated with CysC-defined AKI. For interleukin 18 and
Biering-Sørensen, Fin; Biering-Sørensen, Tor; Liu, Nan; Malmqvist, Lasse; Wecht, Jill Maria; Krassioukov, Andrei
A spinal cord injury (SCI) interferes with the autonomic nervous system (ANS). The effect on the cardiovascular system will depend on the extent of damage to the spinal/central component of ANS. The cardiac changes are caused by loss of supraspinal sympathetic control and relatively increased parasympathetic cardiac control. Decreases in sympathetic activity result in heart rate and the arterial blood pressure changes, and may cause arrhythmias, in particular bradycardia, with the risk of cardiac arrest in those with cervical or high thoracic injuries. The objective of this review is to give an update of the current knowledge related to the alterations in cardiac autonomic control following SCI. With this purpose the review includes the following subheadings: 2. Neuro-anatomical plasticity and cardiac control 2.1 Autonomic nervous system and the heart 2.2 Alteration in autonomic control of the heart following spinal cord injury 3. Spinal shock and neurogenic shock 3.1 Pathophysiology of spinal shock 3.2 Pathophysiology of neurogenic shock 4. Autonomic dysreflexia 4.1 Pathophysiology of autonomic dysreflexia 4.2 Diagnosis of autonomic dysreflexia 5. Heart rate/electrocardiography following spinal cord injury 5.1 Acute phase 5.2 Chronic phase 6. Heart rate variability 6.1 Time domain analysis 6.2 Frequency domain analysis 6.3 QT-variability index 6.4 Nonlinear (fractal) indexes 7. Echocardiography 7.1 Changes in cardiac structure following spinal cord injury 7.2 Changes in cardiac function following spinal cord injury 8. International spinal cord injury cardiovascular basic data set and international standards to document the remaining autonomic function in spinal cord injury.
Gorguner, Metin; Akgun, Metin
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
Bem, Reinout A; van den Berg, Elske; Suidgeest, Ernst; van der Weerd, Louise; van Woensel, Job B M; Grotenhuis, Heynric B
To determine biventricular cardiac function in pneumovirus-induced acute lung injury in spontaneously breathing mice. Experimental animal study. Animal laboratory. C57Bl/6 mice. Mice were inoculated with the rodent pneumovirus, pneumonia virus of mice. Pneumonia virus of mice-infected mice were studied for right and left ventricular function variables by high-field strength (7 Tesla) cardiac MRI at specific time points during the course of disease compared with baseline. One day before and at peak disease severity, pneumonia virus of mice-infected mice showed significant right and left ventricular systolic and diastolic volume changes, with a progressive decrease in stroke volume and ejection fraction. No evidence for viral myocarditis or viral presence in heart tissue was found. These findings show adverse pulmonary-cardiac interaction in pneumovirus-induced acute lung injury, unrelated to direct virus-mediated effects on the heart.
Zuk, Anna; Bonventre, Joseph V.
Acute kidney injury (AKI) is a global public health concern associated with high morbidity, mortality, and healthcare costs. Other than dialysis, no therapeutic interventions reliably improve survival, limit injury, or speed recovery. Despite recognized shortcomings of in vivo animal models, the underlying pathophysiology of AKI and its consequence, chronic kidney disease (CKD), is rich with biological targets. We review recent findings relating to the renal vasculature and cellular stress responses, primarily the intersection of the unfolded protein response, mitochondrial dysfunction, autophagy, and the innate immune response. Maladaptive repair mechanisms that persist following the acute phase promote inflammation and fibrosis in the chronic phase. Here macrophages, growth-arrested tubular epithelial cells, the endothelium, and surrounding pericytes are key players in the progression to chronic disease. Better understanding of these complex interacting pathophysiological mechanisms, their relative importance in humans, and the utility of biomarkers will lead to therapeutic strategies to prevent and treat AKI or impede progression to CKD or end-stage renal disease (ESRD). PMID:26768243
Rosenbaum, Yoseph A; Awan, Hisham M
Hand and wrist injuries in athletes are common, representing between 3 and 25% of all sports injuries. As many as a quarter of all sports injuries involve the hand or wrist. We review the recent literature regarding acute hand injuries in athletes based on the structures involved - bone, muscle/tendon, ligament, and neurovascular - including diagnosis and pathophysiology of these injuries, focusing on athlete-specific facets of treatment, and when available, opinions on return to play.
Kim, Chul; Choi, Hee Eun; Kang, Seong Hoon
Objective To examine the safety and effectiveness of cardiac rehabilitation on patients resuscitated from cardiac arrest due to acute myocardial infarction. Methods The study included 23 subjects, including 8 with history of cardiac arrest and 15 without history of cardiac arrest. Both groups underwent initial graded exercise test (GXT) and subsequent cardiac rehabilitation for 6 weeks. After 6 weeks, both groups received follow-up GXT. Results Statistically significant (p<0.05) increase of VO2peak and maximal MVO2 but significant (p<0.05) decrease of submaximal MVO2 and resting heart rate were observed in both groups after 6 weeks of cardiac rehabilitation. An increasing trend of maximal heart rates was observed in both groups. However, the increase was not statistically significant (p>0.05). There was no statistically significant change of resting heart rate, maximal heart rate, maximal MVO2, or submaximal MVO2 in both groups after cardiac rehabilitation. Fatal cardiac complications, such as abnormal ECG, cardiac arrest, death or myocardial infarction, were not observed. All subjects finished the cardiac rehabilitation program. Conclusion Improvement was observed in the exercise capacity of patients after aerobic exercise throughout the cardiac rehabilitation program. Therefore, cardiac rehabilitation can be safely administered for high-risk patients with history of cardiac arrest. Similar improvement in exercise capacity can be expected in patients without cardiac arrest experience. PMID:25566479
Fadel, Fatina I.; Mohamed, Mohamed Farouk; Habib, Sonia A.; Ibrahim, Mona H.; Sleem, Zeinab S.; Bazaraa, Hafez M.; Soliman, Mohamed M.A.
Introduction Cardiopulmonary bypass (CPB) surgery is considered one of the most frequent surgical procedures in which acute kidney injury (AKI) represents a frequent and serious complication. The aim of the present study was to evaluate the efficiency of neutrophil gelatinase-associated lipocalin (NGAL) as an early AKI biomarker after CPB in pediatric cardiac surgery. Material and methods The study included forty children aged 2 to 78 months undergoing CPB. They were divided into group I: patients who suffered AKI grades II and III; and group II: patients who did not develop AKI or at risk. Peripheral venous blood was withdrawn pre- and post-operatively for serial measurements of NGAL and creatinine. Statistical analysis was performed using Statistical Package for Social Sciences version 14. Results Mean plasma NGAL levels showed highly significant elevations in group I patients at 2, 12, and 24 h after surgery (p < 0.0001) compared to group II. Significant correlations were found between NGAL and creatinine at different time intervals. Highly significant correlations (p < 0.0001) were found between plasma NGAL and AKI at 2, 12 and 24 h after surgery. A cut-off level of 100 ng/ml at 2 h, and 125 ng/ml at 12 h post-operatively both recorded the highest accuracy, being 95% accurate, with sensitivity of 100% and 89.5% respectively, and specificity of 90.5% and 100% respectively. Conclusions This study showed that plasma NGAL could be used as an early biomarker for detection of AKI following CPB. We recommend further studies on a wider scale to validate the current study results. PMID:22661997
Miller, Christopher A; Naish, Josephine H; Shaw, Steven M; Yonan, Nizar; Williams, Simon G; Clark, David; Bishop, Paul W; Ainslie, Mark P; Borg, Alex; Coutts, Glyn; Parker, Geoffrey J M; Ray, Simon G; Schmitt, Matthias
Serial surveillance endomyocardial biopsies are performed in patients who have recently undergone heart transplantation in order to detect acute cardiac allograft rejection (ACAR) before symptoms occur, however the biopsy process is associated with a number of limitations. This study aimed to prospectively and longitudinally evaluate the performance of multiparametric cardiovascular magnetic resonance (CMR) for detecting and monitoring ACAR in the early phase post-transplant, and characterize graft recovery following transplantation. All patients receiving a heart transplant at a single UK centre over a period of 25 months were approached within one month of transplantation. Multiparametric CMR was prospectively performed on the same day as biopsy on four separate occasions (6 weeks, 10 weeks, 15 weeks and 20 weeks post-transplant). CMR included assessment of global and regional ventricular function, myocardial tissue characterization (T1 mapping, T2 mapping, extracellular volume, LGE) and pixel-wise absolute myocardial blood flow quantification. CMR parameters were compared with biopsy findings. As is standard, grade 2R or higher ACAR was considered significant. 88 CMR-matched biopsies were performed in 22 patients. Eight (9%) biopsies in 5 patients demonstrated significant ACAR. Significant ACAR was associated with a reduction in circumferential strain (-12.7±2.5% vs. -13.7±3.6%, p=0.047) but there was considerable overlap between groups. Whilst trends were observed between ACAR and proposed CMR markers of oedema, particularly after adjusting for primary graft dysfunction, differences were not significant. Significant improvements were seen in markers of graft structure and contractility, oedema and microvascular function over the period studied, although few parameters normalised. This study provides novel insight into the myocardial injury associated with transplantation, and its recovery, however multiparametric CMR was not able to accurately detect ACAR
Hori, Daijiro; Hogue, Charles; Adachi, Hideo; Max, Laura; Price, Joel; Sciortino, Christopher; Zehr, Kenton; Conte, John; Cameron, Duke; Mandal, Kaushik
Perioperative blood pressure management by targeting individualized optimal blood pressure, determined by cerebral blood flow autoregulation monitoring, may ensure sufficient renal perfusion. The purpose of this study was to evaluate changes in the optimal blood pressure for individual patients, determined during cardiopulmonary bypass (CPB) and during early postoperative period in intensive care unit (ICU). A secondary aim was to examine if excursions below optimal blood pressure in the ICU are associated with risk of cardiac surgery-associated acute kidney injury (CSA-AKI). One hundred and ten patients undergoing cardiac surgery had cerebral blood flow monitored with a novel technology using ultrasound tagged near infrared spectroscopy (UT-NIRS) during CPB and in the first 3 h after surgery in the ICU. The correlation flow index (CFx) was calculated as a moving, linear correlation coefficient between cerebral flow index measured using UT-NIRS and mean arterial pressure (MAP). Optimal blood pressure was defined as the MAP with the lowest CFx. Changes in optimal blood pressure in the perioperative period were observed and the association of blood pressure excursions (magnitude and duration) below the optimal blood pressure [area under the curve (AUC) < OptMAP mmHgxh] with incidence of CSA-AKI (defined using Kidney Disease: Improving Global Outcomes criteria) was examined. Optimal blood pressure during early ICU stay and CPB was correlated (r = 0.46, P < 0.0001), but was significantly higher in the ICU compared with during CPB (75 ± 8.7 vs 71 ± 10.3 mmHg, P = 0.0002). Thirty patients (27.3%) developed CSA-AKI within 48 h after the surgery. AUC < OptMAP was associated with CSA-AKI during CPB [median, 13.27 mmHgxh, interquartile range (IQR), 4.63-20.14 vs median, 6.05 mmHgxh, IQR 3.03-12.40, P = 0.008], and in the ICU (13.72 mmHgxh, IQR 5.09-25.54 vs 5.65 mmHgxh, IQR 1.71-13.07, P = 0.022). Optimal blood pressure during CPB and in the ICU was correlated. Excursions
Hori, Daijiro; Hogue, Charles; Adachi, Hideo; Max, Laura; Price, Joel; Sciortino, Christopher; Zehr, Kenton; Conte, John; Cameron, Duke; Mandal, Kaushik
OBJECTIVES Perioperative blood pressure management by targeting individualized optimal blood pressure, determined by cerebral blood flow autoregulation monitoring, may ensure sufficient renal perfusion. The purpose of this study was to evaluate changes in the optimal blood pressure for individual patients, determined during cardiopulmonary bypass (CPB) and during early postoperative period in intensive care unit (ICU). A secondary aim was to examine if excursions below optimal blood pressure in the ICU are associated with risk of cardiac surgery-associated acute kidney injury (CSA-AKI). METHODS One hundred and ten patients undergoing cardiac surgery had cerebral blood flow monitored with a novel technology using ultrasound tagged near infrared spectroscopy (UT-NIRS) during CPB and in the first 3 h after surgery in the ICU. The correlation flow index (CFx) was calculated as a moving, linear correlation coefficient between cerebral flow index measured using UT-NIRS and mean arterial pressure (MAP). Optimal blood pressure was defined as the MAP with the lowest CFx. Changes in optimal blood pressure in the perioperative period were observed and the association of blood pressure excursions (magnitude and duration) below the optimal blood pressure [area under the curve (AUC) < OptMAP mmHgxh] with incidence of CSA-AKI (defined using Kidney Disease: Improving Global Outcomes criteria) was examined. RESULTS Optimal blood pressure during early ICU stay and CPB was correlated (r = 0.46, P < 0.0001), but was significantly higher in the ICU compared with during CPB (75 ± 8.7 vs 71 ± 10.3 mmHg, P = 0.0002). Thirty patients (27.3%) developed CSA-AKI within 48 h after the surgery. AUC < OptMAP was associated with CSA-AKI during CPB [median, 13.27 mmHgxh, interquartile range (IQR), 4.63–20.14 vs median, 6.05 mmHgxh, IQR 3.03–12.40, P = 0.008], and in the ICU (13.72 mmHgxh, IQR 5.09–25.54 vs 5.65 mmHgxh, IQR 1.71–13.07, P = 0.022). CONCLUSIONS Optimal blood pressure during
Kallet, Richard H; Matthay, Michael A
Prolonged breathing of very high FIO2 (FIO2 ≥ 0.9) uniformly causes severe hyperoxic acute lung injury (HALI) and, without a reduction of FIO2, is usually fatal. The severity of HALI is directly proportional to PO2 (particularly above 450 mm Hg, or an FIO2 of 0.6) and exposure duration. Hyperoxia produces extraordinary amounts of reactive O2 species that overwhelms natural antioxidant defenses and destroys cellular structures through several pathways. Genetic predisposition has been shown to play an important role in HALI among animals, and some genetics-based epidemiologic research suggests that this may be true for humans as well. Clinically, the risk of HALI likely occurs when FIO2exceeds 0.7, and may become problematic when FIO2 exceeds 0.8 for an extended period of time. Both high-stretch mechanical ventilation and hyperoxia potentiate lung injury and may promote pulmonary infection. During the 1960s, confusion regarding the incidence and relevance of HALI largely reflected such issues as the primitive control of FIO2, the absence of PEEP, and the fact that at the time both ALI and ventilator-induced lung injury were unknown. The advent of PEEP and precise control over FIO2, as well as lung-protective ventilation, and other adjunctive therapies for severe hypoxemia, has greatly reduced the risk of HALI for the vast majority of patients requiring mechanical ventilation in the 21st century. However, a subset of patients with very severe ARDS requiring hyperoxic therapy is at substantial risk for developing HALI, therefore justifying the use of such adjunctive therapies. PMID:23271823
Piano, Salvatore; Tonon, Marta; Angeli, Paolo
Ascites is the most common complication of cirrhosis. Ascites develops as a consequence of an abnormal splanchnic vasodilation with reduction of effecting circulating volume and activation of endogenous vasoconstrictors system causing salt and water retention. Patients with ascites have a high risk to develop further complications of cirrhosis such as hyponatremia, spontaneous bacterial peritonitis and acute kidney injury resulting in a poor survival. In recent years, new studies helped a better understanding of the pathophysiology of ascites and acute kidney injury in cirrhosis. Furthermore, new diagnostic criteria have been proposed for acute kidney injury and hepatorenal syndrome and a new algorithm for their management has been recommended with the aim of an early diagnosis and treatment. Herein we will review the current knowledge on the pathophysiology, diagnosis and treatment of ascites and acute kidney injury in patients with cirrhosis and we will identify the unmet needs that should be clarified in the next years.
Mokra, Daniela; Kosutova, Petra
Acute respiratory distress syndrome (ARDS) and its milder form acute lung injury (ALI) may result from various diseases and situations including sepsis, pneumonia, trauma, acute pancreatitis, aspiration of gastric contents, near-drowning etc. ALI/ARDS is characterized by diffuse alveolar injury, lung edema formation, neutrophil-derived inflammation, and surfactant dysfunction. Clinically, ALI/ARDS is manifested by decreased lung compliance, severe hypoxemia, and bilateral pulmonary infiltrates. Severity and further characteristics of ALI/ARDS may be detected by biomarkers in the plasma and bronchoalveolar lavage fluid (or tracheal aspirate) of patients. Changed concentrations of individual markers may suggest injury or activation of the specific types of lung cells-epithelial or endothelial cells, neutrophils, macrophages, etc.), and thereby help in diagnostics and in evaluation of the patient's clinical status and the treatment efficacy. This chapter reviews various biomarkers of acute lung injury and evaluates their usefulness in diagnostics and prognostication of ALI/ARDS.
Patschan, Daniel; Müller, Gerhard Anton
Acute kidney injury is a frequent and serious complication in hospitalized patients. Mortality rates have not substantially been decreased during the last 20 years. In most patients AKI results from transient renal hypoperfusion or ischemia. The consequences include tubular cell dysfunction/damage, inflammation of the organ, and post-ischemic microvasculopathy. The two latter events perpetuate kidney damage in AKI. Clinical manifestations result from diminished excretion of water, electrolytes, and endogenous / exogenous waste products. Patients are endangered by cardiovascular complications such as hypertension, heart failure, and arrhythmia. In addition, the whole organism may be affected by systemic toxification (uremia). The diagnostic approach in AKI involves several steps with renal biopsy inevitable in some patients. The current therapy focuses on preventing further kidney damage and on treatment of complications. Different pharmacological strategies have failed to significantly improve prognosis in AKI. If dialysis treatment becomes mandatory, intermittent and continuous renal replacement therapies are equally effective. Thus, new therapies are urgently needed in order to reduce short- and long-term outcome in AKI. In this respect, stem cell-based regimens may offer promising perspectives. © 2015 KUMS, All rights reserved.
Early acute kidney injury in military casualties Kelly D. Heegard, MD, Ian J. Stewart, MD, Andrew P. Cap, MD, PhD, Jonathan A. Sosnov, MD, Hana K...Ikizler, MD, and Kevin K. Chung, MD, San Antonio, Texas BACKGROUND: While acute kidney injury (AKI) has been well studied in a variety of patient settings...and epidemiologic study, level III. KEY WORDS: Acute kidney injury; trauma; war; lactate; Injury Severity Score. Acute kidney injury (AKI) is commonly
Schlüter-Brust, K; Leistenschneider, P; Dargel, J; Springorum, H P; Eysel, P; Michael, J W-P
Although Taekwondo is becoming an increasingly popular sport, there is a lack of reliable epidemiologic data on Taekwondo injuries. To perform an epidemiologic study on the variety of types of injury in professional and amateur Taekwondo athletes and to find a relation between Taekwondo style, skill level, weight-class and warm-up routine and the occurrence of injuries, we analysed the injury data using a 7-page questionnaire from a total of 356 Taekwondo athletes who were randomly selected. Overall, we registered a total of 2,164 injuries in 356 athletes. Most traumas were contusions and sprains in the lower extremities. Professional Taekwondo athletes have an increased risk of injury in comparison to recreational athletes. Taekwondo style, weight class and tournament frequency have an influence on the athlete's injury profile. Warm-up routines were found to have a positive effect on injury rates. Overall, Taekwondo may be considered a rather benign activity, if injuries during Taekwondo tournaments can be avoided. If not, Taekwondo can result in serious musculoskeletal problems. © Georg Thieme Verlag KG Stuttgart · New York.
Aghabiklooei, Abbas; Mostafazadeh, Babak; Farzaneh, Esmaeil; Morteza, Afsaneh
Organophosphates are insecticides which are widely used as a suicidal agent in Iran. They are associated with different types of cardiac complications including cardiac arrest and arrhythmia, however their role in cardiac injury is not known yet. The aim of this study was to investigate the presence of myocardial damage in patients with cholinesterase poisoning.It was a prospective study conducted from January 2008 to March 2010. Cohorts of patients with cholinesterase poisoning due to suicidal attempt who have been referred to Loghman hospital were selected. Patients who have taken more than one poison or were used concomitant drugs were excluded. Physical examination was performed on admission to discover warning sign. Peripheral arterial blood gases, creatine kinase, creatine kinase-myocardial band, troponin-T measurements were performed in all cases. There were 24 patients, 7 of them women, with the mean age of 41.2±15.05 who were included in this study. Non-survivors had significantly higher levels of systolic blood pressure, partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide, bicarbonate Glasgow Coma Scale scoring and longer duration of mechanical ventilation. Our findings showed that cardiac injury is an important cause of death in organophosphate poisoning. It could be hypothesized that cardiac injury is a strong predictor of death in patients with organophosphate poisoning.
Hocker, Sara; Prasad, Abhiram; Rabinstein, Alejandro A
We sought to describe the spectrum of cardiac injury in refractory status epilepticus (RSE). We reviewed all patients with RSE between 1999 and 2011 at Mayo Clinic. RSE was defined as generalized convulsive or nonconvulsive status epilepticus (SE) that continued despite initial therapies. Exclusion criteria were age <18 years, anoxic SE, psychogenic SE, simple partial SE, absence SE, and repeat RSE. Patients were divided into those with (transient left ventricular [LV] dysfunction; electrocardiography [ECG] abnormality-new T-wave inversion, ST elevation or ST depression, or QTc prolongation; and/or elevated blood troponin T levels) versus those without evidence of cardiac injury. We identified 59 consecutive patients with RSE. In 24 patients no cardiac-specific diagnostic studies were obtained. Twenty-two of the remaining 35 patients demonstrated markers of cardiac injury. General anesthesia was necessary for control of seizures in 31 of 35 patients for 10.5 ± 17.4 days. Twenty-three patients had troponin levels drawn at onset of SE, of which nine were abnormal. ECG findings at onset of SE included ST elevation (11.4%), ST depression (5.7%), new T-wave inversion (37.1%), and nonspecific ST changes (37.1%). Cardiac arrhythmias included ventricular tachycardia/fibrillation (11.4%), atrioventricular block (2.9%), atrial fibrillation/flutter (20.0%), sinus bradycardia (48.6%), and sinus tachycardia (65.7%). Intervention was required for cardiac arrhythmias in 42.9%. QTc was prolonged in 22.9% of patients. One patient met criteria for non-ST-elevation myocardial infarction (NSTEMI). Three of 14 patients evaluated with ECG during SE demonstrated reversible systolic dysfunction. In-hospital mortality was 34.3%. Outcome was worse in the group with markers of cardiac injury but the difference was not statistically significant (p = 0.14). Markers of cardiac injury are common in RSE and may be underrecognized in this population. These disturbances may require specific
Sweetman, Deirdre U
Neonatal acute kidney injury is common, in part due to incomplete renal maturation and also due to frequent exposure to risk factors for acute kidney injury such as perinatal asphyxia, extracorporeal-membrane-oxygenation, cardiac surgery, sepsis, prematurity and nephrotoxicity. However the current method by which acute kidney injury is diagnosed is sub-optimal and not universally accepted which impairs the accurate estimation of the true incidence of neonatal acute kidney injury. Serum Cystatin-C, urinary NGAL, KIM-1 and IL-18 are promising neonatal acute kidney injury biomarkers however the diagnosis of acute kidney injury remains serum creatinine/urine output-based in many studies. Emerging biomarkers which require further study in the neonatal population include netrin-1 and EGF. Increased awareness amongst clinicians of nephrotoxic medications being a modifiable risk factor for the development of neonatal acute kidney injury is imperative. The burden of chronic kidney failure following neonatal acute kidney injury is unclear and requires further study.
Reyes, Luis F; Restrepo, Marcos I; Hinojosa, Cecilia A; Soni, Nilam J; Anzueto, Antonio; Babu, Bettina L; Gonzalez-Juarbe, Norberto; Rodriguez, Alejandro H; Jimenez, Alejandro; Chalmers, James D; Aliberti, Stefano; Sibila, Oriol; Winter, Vicki T; Coalson, Jacqueline J; Giavedoni, Luis D; Dela Cruz, Charles S; Waterer, Grant W; Witzenrath, Martin; Suttorp, Norbert; Dube, Peter H; Orihuela, Carlos J
Up to one-third of patients hospitalized with pneumococcal pneumonia experience major adverse cardiac events (MACE) during or after pneumonia. In mice, Streptococcus pneumoniae can invade the myocardium, induce cardiomyocyte death, and disrupt cardiac function following bacteremia, but it is unknown whether the same occurs in humans with severe pneumonia. We sought to determine whether S. pneumoniae can (1) translocate the heart, (2) induce cardiomyocyte death, (3) cause MACE, and (4) induce cardiac scar formation after antibiotic treatment during severe pneumonia using a nonhuman primate (NHP) model. We examined cardiac tissue from six adult NHPs with severe pneumococcal pneumonia and three uninfected control animals. Three animals were rescued with antibiotics (convalescent animals). Electrocardiographic, echocardiographic, and serum biomarkers of cardiac damage were measured (troponin T, N-terminal pro-brain natriuretic peptide, and heart-type fatty acid binding protein). Histological examination included hematoxylin and eosin staining, immunofluorescence, immunohistochemistry, picrosirius red staining, and transmission electron microscopy. Immunoblots were used to assess the underlying mechanisms. Nonspecific ischemic alterations were detected by electrocardiography and echocardiography. Serum levels of troponin T and heart-type fatty acid binding protein were increased (P < 0.05) after pneumococcal infection in both acutely ill and convalescent NHPs. S. pneumoniae was detected in the myocardium of all NHPs with acute severe pneumonia. Necroptosis and apoptosis were detected in the myocardium of both acutely ill and convalescent NHPs. Evidence of cardiac scar formation was observed only in convalescent animals by transmission electron microscopy and picrosirius red staining. S. pneumoniae invades the myocardium and induces cardiac injury with necroptosis and apoptosis, followed by cardiac scarring after antibiotic therapy, in an NHP model of severe
Khalid, A.; Chan, B. T.; Lim, E.; Liew, Y. M.
Acute myocardial infarction (AMI) is the most severe form of coronary artery disease leading to localized myocardial injury and therefore irregularities in the cardiac wall contractility. Studies have found very limited differences in global indices (such as ejection fraction, myocardial mass and volume) between healthy subjects and AMI patients, and therefore suggested regional assessment. Regional index, specifically cardiac wall thickness (WT) and thickening is closely related to cardiac function and could reveal regional abnormality due to AMI. In this study, we developed a 3D wall thickening assessment method to identify regional wall contractility dysfunction due to localized myocardial injury from infarction. Wall thickness and thickening were assessed from 3D personalized cardiac models reconstructed from cine MRI images by fitting inscribed sphere between endocardial and epicardial wall. The thickening analysis was performed in 5 patients and 3 healthy subjects and the results were compared against the gold standard 2D late-gadolinium-enhanced (LGE) images for infarct localization. The notable finding of this study is the highly accurate estimation and visual representation of the infarct size and location in 3D. This study provides clinicians with an intuitive way to visually and qualitatively assess regional cardiac wall dysfunction due to infarction in AMI patients.
Monica, James; Vredenburgh, Zachary; Korsh, Jeremy; Gatt, Charles
Acute shoulder injuries in adults are often initially managed by family physicians. Common acute shoulder injuries include acromioclavicular joint injuries, clavicle fractures, glenohumeral dislocations, proximal humerus fractures, and rotator cuff tears. Acromioclavicular joint injuries and clavicle fractures mostly occur in young adults as the result of a sports injury or direct trauma. Most nondisplaced or minimally displaced injuries can be treated conservatively. Treatment includes pain management, short-term use of a sling for comfort, and physical therapy as needed. Glenohumeral dislocations can result from contact sports, falls, bicycle accidents, and similar high-impact trauma. Patients will usually hold the affected arm in their contralateral hand and have pain with motion and decreased motion at the shoulder. Physical findings may include a palpable humeral head in the axilla or a dimple inferior to the acromion laterally. Reduction maneuvers usually require intra-articular lidocaine or intravenous analgesia. Proximal humerus fractures often occur in older patients after a low-energy fall. Radiography of the shoulder should include a true anteroposterior view of the glenoid, scapular Y view, and axillary view. Most of these fractures can be managed nonoperatively, using a sling, early range-of-motion exercises, and strength training. Rotator cuff tears can cause difficulty with overhead activities or pain that awakens the patient from sleep. On physical examination, patients may be unable to hold the affected arm in an elevated position. It is important to recognize the sometimes subtle signs and symptoms of acute shoulder injuries to ensure proper management and timely referral if necessary.
Veiersted, Kaj Bo; Goffeng, Lars Ole; Moian, Rune; Remo, Eirik; Solli, Are; Erikssen, Jan
Electrical accidents are potentially fatal incidents with effect on the cardiovascular, nerve and musculoskeletal systems and on the skin (burns). The electrical engineering industry points out that the follow-up of injured persons from site of accident to hospital is quite random. This paper gives a review of the current literature and proposes guidelines for the follow-up of victims of electrical accidents. A search of the literature was conducted on Medline, Embase, Biosis, Healthline, the Cochrane Library, the ISI citation databases, and on several other search engines. The revised guidelines were developed in consultation with 23 medical and industry institutions. Serious acute effects of electrical accidents include cardiac arrest, respiration failure, burns (also (internal burns) with necrosis of e.g. muscle tissue), injuries to the nerve system, and renal failure. Traumas caused by falls are also frequent. Possible chronic effects are mostly seen in the nerve system as encephalopathy and psychological sequelae or as spinal cord and peripheral nerve injury. Most importantly, long latent periods are possible for some chronic nerve injuries. This paper suggest guidelines for acute (on the spot) action and criteria for referral to hospital, observation in hospital and further follow-up.
Rong, Lisa Q.; Di Franco, Antonino
Acute respiratory distress syndrome (ARDS) is a leading cause of postoperative respiratory failure, with a mortality rate approaching 40% in the general population and 80% in the subset of patients undergoing cardiac surgery. The increased risk of ARDS in these patients has traditionally been associated with the use of cardiopulmonary bypass (CPB), the need for blood product transfusions, large volume shifts, mechanical ventilation and direct surgical insult. Indeed, the impact of ARDS in the cardiac population is substantial, affecting not only survival but also in-hospital length of stay and long-term physical and psychological morbidity. No patient undergoing cardiac surgery can be considered ARDS risk-free. Early identification of those at higher risk is crucial to warrant the adoption of both surgical and non-surgical specific preventative strategies. The present review focuses on epidemiology, risk assessment, pathophysiology, prevention and management of ARDS in the specific setting of patients undergoing cardiac surgery. PMID:27867583
Schaub, Jennifer A.; Parikh, Chirag R.
Acute kidney injury is strongly associated with increased mortality and other adverse outcomes. Medical researchers have intensively investigated novel biomarkers to predict short- and long-term outcomes of acute kidney injury in many patient care settings, such as cardiac surgery, intensive care units, heart failure, and transplant. Future research should focus on leveraging this relationship to improve enrollment for clinical trials of acute kidney injury. PMID:27239295
Chen, Yu-Chin; Tseng, Yi-Chia; Huang, Wen-Hung; Hsu, Ching-Wei; Weng, Cheng-Hao; Liu, Shou-Hsuan; Yang, Huang-Yu; Chen, Kuan-Hsin; Chen, Hui-Ling; Fu, Jen-Fen; Lin, Wey-Ran; Wang, I-Kuan; Yen, Tzung-Hai
A paucity of literature exists on risk factors for mortality in charcoal burning suicide. In this observational study, we analyzed the data of 126 patients with charcoal burning suicide that seen between 2002 and 2013. Patients were grouped according to status of renal damage as acute kidney injury (N = 49) or non-acute kidney injury (N = 77). It was found that patients with acute kidney injury suffered severer complications such as respiratory failure (P = 0.002), myocardial injury (P = 0.049), hepatic injury (P < 0.001), rhabdomyolysis (P = 0.045) and out-of-hospital cardiac arrest (P = 0.028) than patients without acute kidney injury. Moreover, patients with acute kidney injury suffered longer hospitalization duration (16.9 ± 18.3 versus 10.7 ± 10.9, P = 0.002) and had higher mortality rate (8.2% versus 0%, P = 0.011) than patients without injury. In a multivariate Cox regression model, it was demonstrated that serum creatinine level (P = 0.019) and heart rate (P = 0.022) were significant risk factors for mortality. Finally, Kaplan-Meier analysis revealed that patients with acute kidney injury suffered lower cumulative survival than without injury (P = 0.016). In summary, the overall mortality rate of charcoal burning suicide population was 3.2%, and acute kidney injury was a powerful predictor of mortality. Further studies are warranted. PMID:27430168
Ziegelstein, Roy C
Episodes of acute emotional stress can have significant adverse effects on the heart. Acute emotional stress can produce left ventricular contractile dysfunction, myocardial ischemia, or disturbances of cardiac rhythm. Although these abnormalities are often only transient, their consequences can be gravely damaging and sometimes fatal. Despite the many descriptions of catastrophic cardiovascular events in the setting of acute emotional stress, the anatomical substrate and physiological pathways by which emotional stress triggers cardiovascular events are only now being characterized, aided by the advent of functional neuroimaging. Recent evidence indicates that asymmetric brain activity is particularly important in making the heart more susceptible to ventricular arrhythmias. Lateralization of cerebral activity during emotional stress may stimulate the heart asymmetrically and produce areas of inhomogeneous repolarization that create electrical instability and facilitate the development of cardiac arrhythmias. Patients with ischemic heart disease who survive an episode of sudden cardiac death in the setting of acute emotional stress should receive a beta-blocker. Nonpharmacological approaches to manage emotional stress in patients with and without coronary artery disease, including social support, relaxation therapy, yoga, meditation, controlled slow breathing, and biofeedback, are also appropriate to consider and merit additional investigation in randomized trials.
Bilgili, Beliz; Haliloğlu, Murat; Cinel, İsmail
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.
Bilgili, Beliz; Haliloğlu, Murat; Cinel, İsmail
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. PMID:27366441
Hammer, Mark M; Raptis, Demetrios A; Cummings, Kristopher W; Mellnick, Vincent M; Bhalla, Sanjeev; Schuerer, Douglas J; Raptis, Constantine A
Blunt cardiac injury (BCI) may manifest as cardiac contusion or, more rarely, as pericardial or myocardial rupture. Computed tomography (CT) is performed in the vast majority of blunt trauma patients, but the imaging features of cardiac contusion are not well described. To evaluate CT findings and associated injuries in patients with clinically diagnosed BCI. We identified 42 patients with blunt cardiac injury from our institution's electronic medical record. Clinical parameters, echocardiography results, and laboratory tests were recorded. Two blinded reviewers analyzed chest CTs performed in these patients for myocardial hypoenhancement and associated injuries. CT findings of severe thoracic trauma are commonly present in patients with severe BCI; 82% of patients with ECG, cardiac enzyme, and echocardiographic evidence of BCI had abnormalities of the heart or pericardium on CT; 73% had anterior rib fractures, and 64% had pulmonary contusions. Sternal fractures were only seen in 36% of such patients. However, myocardial hypoenhancement on CT is poorly sensitive for those patients with cardiac contusion: 0% of right ventricular contusions and 22% of left ventricular contusions seen on echocardiography were identified on CT. CT signs of severe thoracic trauma are frequently present in patients with severe BCI and should be regarded as indirect evidence of potential BCI. Direct CT findings of myocardial contusion, i.e. myocardial hypoenhancement, are poorly sensitive and should not be used as a screening tool. However, some left ventricular contusions can be seen on CT, and these patients could undergo echocardiography or cardiac MRI to evaluate for wall motion abnormalities. Copyright © 2015 Elsevier Ltd. All rights reserved.
Basile, David P.; Anderson, Melissa D.; Sutton, Timothy A.
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
Taha, Doaa; Anggraini, Fika; Degracia, Donald; Huang, Zhi-Feng
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.
Ralto, Kenneth M.; Parikh, Samir M.
Acute kidney injury (AKI) continues to be a significant contributor to morbidity, mortality and healthcare expenditure. In the United States alone, it is estimated that over $10 billion is spent on AKI every year1. Currently, there are no available therapies to treat established AKI. The mitochondrion is positioned to be a critical player in AKI with its dual role as the primary source of energy for each cell and as a key regulator of cell death. This review aims to cover the current state of research on the role of mitochondria in AKI while also proposing potential therapeutic targets and future therapies. PMID:27085731
Wetsch, Wolfgang A; Lahm, Tim; Hinkelbein, Jochen; Happel, Christoph M; Padosch, Stephan A
Acute right heart failure (RHF) is a frequent and severe complication during perioperative and intensive care treatment in intensive care units (ICUs). The most common causes are pulmonary hypertension, left heart failure, pulmonary embolism, sepsis, acute lung injury (ALI) and thoracosurgical procedures. Acute RHF is not only a major contributor to morbidity and mortality; it also influences efficacy and outcome of routinely performed procedures, such as vasopressors, in critically ill patients. In contrast to the left ventricle, the right ventricle's physiology and pathophysiology are understudied, and the diagnosis of acute RHF is frequently challenging. Although many drugs are available for the treatment of RHF, randomized trials for this setting are still missing. This article gives an overview of aetiology and pathogenesis of RHF and reviews the diagnostic and therapeutic interventions currently available for providers in anaesthesiology and critical care. © Georg Thieme Verlag Stuttgart · New York.
Leite, Luís; Gonçalves, Lino; Nuno Vieira, Duarte
Assessment of suspected cardiac injuries in a trauma setting is a challenging and time-critical matter, with clinical and imaging findings having complementary roles in the formation of an accurate diagnosis. In this article, we review the supporting literature for the pathophysiology, classification and evaluation of cardiac injuries caused by trauma. We also describe 4 cardiac trauma patients seen at a tertiary referral hospital. Copyright © 2017 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.
Koyner, Jay L.; Bennett, Michael R.; Worcester, Elaine M.; Ma, Qing; Raman, Jai; Jeevanandam, Valluvan; Kasza, Kristen E.; O' Connor, Michael F.; Konczal, David J.; Trevino, Sharon; Devarajan, Prasad; Murray, Patrick T.
There is a need to develop early biomarkers of acute kidney injury following cardiac surgery, where morbidity and mortality are increased by its presence. Plasma cystatin C (CyC) and plasma and urine Neutrophil Gelatinase Associated Lipocalin (NGAL) have been shown to detect kidney injury earlier than changes in plasma creatinine in critically ill patients. In order to determine the utility of urinary CyC levels as a measure of kidney injury, we prospectively collected plasma and urine from 72 adults undergoing elective cardiac surgery for analysis. Acute kidney injury was defined as a 25% or greater increase in plasma creatinine or renal replacement therapy within the first 72 hours following surgery. Plasma CyC and NGAL were not useful predictors of acute kidney injury within the first 6 hours following surgery. In contrast, both urinary CyC and NGAL were elevated in the 34 patients who later developed acute kidney injury, compared to those with no injury. The urinary NGAL at the time of ICU arrival and the urinary CyC level 6 hours after ICU admission were most useful for predicting acute kidney injury. A composite time point consisting of the maximum urinary CyC achieved in the first 6 hours following surgery outperformed all individual time points. Our study suggests that urinary CyC and NGAL are superior to conventional and novel plasma markers in the early diagnosis of acute kidney injury following adult cardiac surgery. PMID:18650797
Pre- and/or Intra-Operative Prescription of Diuretics, but Not Renin-Angiotensin-System Inhibitors, Is Significantly Associated with Acute Kidney Injury after Non-Cardiac Surgery: A Retrospective Cohort Study
Tagawa, Miho; Ogata, Ai; Hamano, Takayuki
Background and Objectives Pre- and/or intra-operative use of diuretics, angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARB) constitutes a potentially modifiable risk factor for postoperative acute kidney injury (AKI). It has been studied whether use of these drugs predicts AKI after cardiac surgery. The objective of this study was to examine whether administration of these agents was independently associated with AKI after non-cardiac surgery. Design, Setting, Participants, and Measurements This was a retrospective observational study. Inclusion criteria were adult patients (age ≥ 18) who underwent non-cardiac surgery under general anesthesia from 2007 to 2009 at Kyoto Katsura Hospital. Exclusion criteria were urological surgery, missing creatinine values, and preoperative dialysis. The exposures of interest were pre- and/or intra-operative use of diuretics or ACE-I/ARB. Outcome variables were postoperative AKI as defined by the AKI Network (increase in creatinine ≥ 0.3 mg/dL or 150% within 48 hours, or urine output < 0.5 ml/kg/hour for > 6 hours). Multivariable logistic regression analyses were conducted and adjusted for potential confounders. Propensity scores (PS) for receiving diuretics or ACE-I/ARB therapy were estimated and PS adjustment, PS matching, and inverse probability weighting were performed. Results There were 137 AKI cases (5.0%) among 2,725 subjects. After statistical adjustment for patient and surgical characteristics, odds (95% CI) of postoperative AKI were 2.07 (1.10-3.89) (p = 0.02) and 0.89 (0.56-1.42) (p = 0.63) in users of diuretics and ACE-I/ARB, respectively, compared with non-users. PS adjustment, PS matching, and inverse probability weighting yielded similar results. The effect size of diuretics was significantly greater in the patients with lower propensity for diuretic use (p for interaction < 0.1). Conclusions Prescription of diuretics, but not ACE-I/ARB, was independently associated with
Pre- and/or Intra-Operative Prescription of Diuretics, but Not Renin-Angiotensin-System Inhibitors, Is Significantly Associated with Acute Kidney Injury after Non-Cardiac Surgery: A Retrospective Cohort Study.
Tagawa, Miho; Ogata, Ai; Hamano, Takayuki
Pre- and/or intra-operative use of diuretics, angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARB) constitutes a potentially modifiable risk factor for postoperative acute kidney injury (AKI). It has been studied whether use of these drugs predicts AKI after cardiac surgery. The objective of this study was to examine whether administration of these agents was independently associated with AKI after non-cardiac surgery. This was a retrospective observational study. Inclusion criteria were adult patients (age ≥ 18) who underwent non-cardiac surgery under general anesthesia from 2007 to 2009 at Kyoto Katsura Hospital. Exclusion criteria were urological surgery, missing creatinine values, and preoperative dialysis. The exposures of interest were pre- and/or intra-operative use of diuretics or ACE-I/ARB. Outcome variables were postoperative AKI as defined by the AKI Network (increase in creatinine ≥ 0.3 mg/dL or 150% within 48 hours, or urine output < 0.5 ml/kg/hour for > 6 hours). Multivariable logistic regression analyses were conducted and adjusted for potential confounders. Propensity scores (PS) for receiving diuretics or ACE-I/ARB therapy were estimated and PS adjustment, PS matching, and inverse probability weighting were performed. There were 137 AKI cases (5.0%) among 2,725 subjects. After statistical adjustment for patient and surgical characteristics, odds (95% CI) of postoperative AKI were 2.07 (1.10-3.89) (p = 0.02) and 0.89 (0.56-1.42) (p = 0.63) in users of diuretics and ACE-I/ARB, respectively, compared with non-users. PS adjustment, PS matching, and inverse probability weighting yielded similar results. The effect size of diuretics was significantly greater in the patients with lower propensity for diuretic use (p for interaction < 0.1). Prescription of diuretics, but not ACE-I/ARB, was independently associated with postoperative AKI after non-cardiac surgery, especially in patients with low propensity for
Lone, Reyaz Ahmed; Wani, Mehmood Ahmad; Hussain, Zahur; Dar, Abdul Majid; Sharma, Mukhand Lal; Bhat, Mohd Akbar; Ahangar, Abdul Gani
Penetrating cardiac trauma represents an increasingly important form of trauma due to the frequent use of firearms and bombs in civilian violence. We report our experience over the past 16 years with missile-induced cardiac injuries. A retrospective study reviewing 40 cases (30 males, 10 females) of missile cardiac injuries was conducted. The nature of injuries, management and outcomes were analyzed. The ages ranged from 14-68 years. The mean time in which patients reached the hospital was 4.1 hours. Forty percent of the patients had firearm injuries and the remaining 60% had pellet or splinter injuries to the heart. Survival was noted in 37.5% in the gunshot group and in 66.6% in the splinter/pellet group. The survival in patients with isolated cardiac injury was 60%, while it was only 40% in those with associated injuries. Single-chamber injury was noted in 87.5% of the patients and the survival in these was 62.8%. Fourteen complications were noted in the patients who were resuscitated. One patient was re-explored for excessive bleeding and a missed right ventricular perforation was repaired. In missile cardiac injuries, results are best if operated early, and outcome depends upon multiple factors including clinical status at arrival, time interval till management, nature of injury, and associated injuries.
Connelly, Tara M; Kolcow, Walenty; Veerasingam, Dave; DaCosta, Mark
Penetrating cardiac injury is rare and frequently not survivable. Significant haemorrhage resulting in cardiac tamponade commonly ensues. Such cardiac tamponade is a clear clinical, radiological and sonographic indicator of significant underlying injury. In the absence of cardiac tamponade, diagnosis can be more challenging. In this case of a 26-year old sailor stabbed at sea, a significant pericardial effusion and cardiac tamponade did not occur despite an injury transversing the pericardium. Instead, the pericardial haemorrhage drained into the left pleural cavity resulting in a haemothorax. This case is notable due to a favourable outcome despite a delay in diagnosis due to a lack of pericardial effusion, a concomitant cerebrovascular event and a long delay from injury to appropriate medical treatment in the presence of a penetrating cardiac wound deep enough to cause a muscular ventricular septal defect and lacerate a primary chordae of the anterior mitral leaflet.
Inhalation of ultrafine carbon particles (ufCP) causes cardiac physiological changes without marked pulmonary injury or inflammation. We hypothesized that acute ufCP exposure of 13 months old Spontaneously Hypertensive (SH) rats will cause differential effects on the lung and hea...
Inhalation of ultrafine carbon particles (ufCP) causes cardiac physiological changes without marked pulmonary injury or inflammation. We hypothesized that acute ufCP exposure of 13 months old Spontaneously Hypertensive (SH) rats will cause differential effects on the lung and hea...
Sherry, Marc A; Johnston, Tyler S; Heiderscheit, Bryan C
Acute hamstring injuries are responsible for significant time loss for athletes. As there are a multitude of injury mechanisms, thorough evaluation is imperative for determining the appropriate plan of care and adequate rehabilitation is required to reduce the risk of recurrent injuries. Copyright © 2015 Elsevier Inc. All rights reserved.
Chalkias, Athanasios; Xanthos, Theodoros
Cardiac arrest is a leading cause of death that affects more than a million individuals worldwide every year. Despite the recent advancement in the field of cardiac arrest and resuscitation, the management and prognosis of post-cardiac arrest brain injury remain suboptimal. The pathophysiology of post-cardiac arrest brain injury involves a complex cascade of molecular events, most of which remain unknown. Considering that a potentially broad therapeutic window for neuroprotective drug therapy is offered in most successfully resuscitated patient after cardiac arrest, the need for further research is imperative. The aim of this article is to present the major pathophysiological disturbances leading to post-cardiac arrest brain injury, as well as to review the available pharmacological therapies.
Chang, Connie Y; Torriani, Martin; Huang, Ambrose J
Rock climbing has increased in popularity as a sport, and specific injuries related to its practice are becoming more common. Chronic repetitive injuries are more common than acute injuries, although acute injuries tend to be more severe. We review both acute and chronic upper and lower extremity injuries. Understanding the injury pattern in rock climbers is important for accurate diagnosis.
Nigwekar, Sagar U; Waikar, Sushrut S
Acute kidney injury (AKI) is common in hospitalized patients and is associated with significant morbidity and mortality. The incidence of AKI is increasing and despite clinical advances there has been little change in the outcomes associated with AKI. A variety of interventions, including loop diuretics, have been tested for the prevention and treatment of AKI; however, none to date have shown convincing benefits in clinical studies, and the management of AKI remains largely supportive. In this article, we review the pharmacology and experimental and clinical evidence for loop diuretics in the management of AKI. In addition, we also review evidence for other agents with diuretic and/or natriuretic properties such as thiazide diuretics, mannitol, fenoldopam, and natriuretic peptides in both the prevention and treatment of AKI. Implications for current clinical practice are outlined to guide clinical decisions in this field. Copyright © 2011 Elsevier Inc. All rights reserved.
Bavare, Aarti C; Rafie, Kimia S; Bastero, Patricia X; Hagan, Joseph L; Checchia, Paul A
We studied rapid response events after acute clinical instability outside ICU settings in pediatric cardiac patients. Our objective was to describe the characteristics and outcomes after rapid response events in this high-risk cohort and elucidate the cardiac conditions and risk factors associated with worse outcomes. A retrospective single-center study was carried out over a 3-year period from July 2011 to June 2014. Referral high-volume pediatric cardiac center located within a tertiary academic pediatric hospital. All rapid response events that occurred during the study period were reviewed to identify rapid response events in cardiac patients. None. We reviewed 1,906 rapid response events to identify 152 rapid response events that occurred in 127 pediatric cardiac patients. Congenital heart disease was the baseline diagnosis in 74% events (single ventricle, 28%; biventricle physiology, 46%). Seventy-four percent had a cardiac surgery before rapid response, 37% had ICU stay within previous 7 days, and acute kidney injury was noted in 41% post rapid response. Cardiac and/or pulmonary arrest occurred during rapid response in 8.5%. Overall, 81% were transferred to ICU, 22% had critical deterioration (ventilation or vasopressors within 12 hr of transfer), and 56% received such support and/or invasive procedures within 72 hours. Mortality within 30 days post event was 14%. Significant outcome associations included: single ventricle physiology-increased need for invasive procedures and mortality (adjusted odds ratio, 2.58; p = 0.02); multiple rapid response triggers-increased ICU transfer and interventions at 72 hours; critical deterioration-cardiopulmonary arrest and mortality; and acute kidney injury-cardiopulmonary arrest and need for hemodynamic support. Congenital heart disease, previous cardiac surgery, and recent discharge from ICU were common among pediatric cardiac rapid responses. Progression to cardiopulmonary arrest during rapid response, need for ICU
Baudouin, S. V.; Howdle, P.; O'Grady, J. G.; Webster, N. R.
BACKGROUND--There is little information on the incidence of acute lung injury or changes in the pulmonary circulation in acute liver failure. The aim of this study was to record the incidence of acute lung injury in fulminant hepatic failure caused by paracetamol poisoning, to document the associated pulmonary circulatory changes, and to assess the impact of lung injury on patient outcome. METHODS--The degree of lung injury was retrospectively assessed by a standard scoring system (modified from Murray) in all patients with fulminant hepatic failure caused by paracetamol poisoning, admitted to the intensive care unit over a one year period. The severity of liver failure and illness, other organ system failure, and patient outcome were also analysed. RESULTS--Twenty four patients with paracetamol-induced liver failure were admitted and nine developed lung injury of whom eight (33%) had severe injury (Murray score > 2.5). In two patients hypoxaemia contributed to death. Patients with lung injury had higher median encephalopathy grades (4 v 2 in the non-injured group) and APACHE II scores (29 v 16). Circulatory failure, requiring vasoconstrictor support, occurred in all patients with lung injury but in only 40% of those without. Cerebral oedema, as detected by abnormal rises in intracranial pressure, also occurred in all patients with lung injury but in only 27% of the non-injured patients. The incidence of renal failure requiring renal replacement therapy was similar in both groups (67% and 47%). Pulmonary artery occlusion pressures were normal in the lung injury group. Cardiac output was high (median 11.2 1/min), systemic vascular resistance low (median 503 dynes/s/cm-5), and pulmonary vascular resistance low (median 70 dynes/s/cm-5), but not significantly different from the group without lung injury. Mortality was much higher in the lung injury group than in the non-injured group (89% v 13%). CONCLUSIONS--Acute lung injury was common in patients with paracetamol
Jim, Belinda; Garovic, Vesna D
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.
Kaewlai, Rathachai; de Moya, Marc A; Santos, Antonio; Asrani, Ashwin V; Avery, Laura L; Novelline, Robert A
Trauma patients with thoracic aortic injury (TAI) suffer blunt cardiac injury (BCI) at variable frequencies. This investigation aimed to determine the frequency of BCI in trauma patients with TAI and compare with those without TAI. All trauma patients with TAI who had admission electrocardiography (ECG) and serum creatine kinase-MB (CK-MB) from January 1999 to May 2009 were included as a study group at a level I trauma center. BCI was diagnosed if there was a positive ECG with either an elevated CK-MB or abnormal echocardiography. There were 26 patients (19 men, mean age 45.1 years, mean ISS 34.4) in the study group; 20 had evidence of BCI. Of 52 patients in the control group (38 men, mean age 46.9 years, mean ISS 38.7), eighteen had evidence of BCI. There was a significantly higher rate of BCI in trauma patients with TAI versus those without TAI (77% versus 35%, P < 0.001).
Kaewlai, Rathachai; de Moya, Marc A.; Santos, Antonio; Asrani, Ashwin V.; Avery, Laura L.; Novelline, Robert A.
Trauma patients with thoracic aortic injury (TAI) suffer blunt cardiac injury (BCI) at variable frequencies. This investigation aimed to determine the frequency of BCI in trauma patients with TAI and compare with those without TAI. All trauma patients with TAI who had admission electrocardiography (ECG) and serum creatine kinase-MB (CK-MB) from January 1999 to May 2009 were included as a study group at a level I trauma center. BCI was diagnosed if there was a positive ECG with either an elevated CK-MB or abnormal echocardiography. There were 26 patients (19 men, mean age 45.1 years, mean ISS 34.4) in the study group; 20 had evidence of BCI. Of 52 patients in the control group (38 men, mean age 46.9 years, mean ISS 38.7), eighteen had evidence of BCI. There was a significantly higher rate of BCI in trauma patients with TAI versus those without TAI (77% versus 35%, P < 0.001). PMID:22046549
Kayatta, Michael O; Vasquez, Julio C; DeLaRosa, Jacob
Iatrogenic intraoperative tracheal injuries are rare in cardiac operations. Management of this complication is not well described because of the low incidence and lack of reported cases. We present an 82-year-old woman who sustained a tracheal injury during aortic valve replacement. Soft tissue coverage of the trachea was obtained, the original cardiac operation was completed, and she was otherwise managed conservatively. She recovered without further complication and was discharged home 1 week after the surgical procedure.
Turdi, Subat; Schamber, Robbie M; Roe, Nathan D; Chew, Herbert G; Culver, Bruce; Ren, Jun
Methamphetamine, a commonly seen substance of abuse, has been reported to exert detrimental effect on bodily function including the cardiovascular system although its mechanism of action is poorly understood. This study was designed to examine the direct impact of methamphetamine on isolated whole heart and single cardiomyocyte contractile function. Murine hearts and isolated cardiomyocytes from adult FVB mice were exposed to various concentrations of methamphetamine for 30min prior to the assessment of mechanical function using a Langendroff apparatus and an IonOptix Myocam system, respectively. Cardiac contractile properties analyzed included maximal velocity of left ventricular pressure development and decline (+/-dP/dt), peak shortening amplitude (PS), maximal velocity of shortening/relengthening (+/-dLdt), time-to-PS (TPS), time-to-90% relengthening (TR(90)), resting and electrically stimulated increase of intracellular Ca(2+) as well as intracellular Ca(2+) decay. Our results revealed that acute methamphetamine exposure depressed +/-dP/dt, PS and rise of intracellular Ca(2+) without affecting +/-dLdt, TPS, TR(90), resting intracellular Ca(2+) and intracellular Ca(2+) decay. Furthermore, methamphetamine nullified the adrenergic agonist norepinephrine-elicited positive cardiomyocyte contractile response, including elevated PS, +/-dLdt and shortened TR(90) without affecting TPS. Western blot analysis showed unchanged expression of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a) and phospholamban, associated with upregulated Na(+)-Ca(2+) exchanger levels following acute methamphetamine exposure. In addition, methamphetamine promoted overt cardiomyocyte protein damage evaluated by carbonyl formation. Taken together, these results demonstrate direct cardiac depressant effect of methamphetamine in myocardium and isolated cardiomyocytes, possibly associated with protein damage and dampened adrenergic response.
Turdi, Subat; Schamber, Robbie M.; Roe, Nathan D.; Chew, Herbert G.; Culver, Bruce; Ren, Jun
Methamphetamine, a commonly seen substance of abuse, has been reported to exert detrimental effect on bodily function including the cardiovascular system although its mechanism of action is poorly understood. This study was designed to examine the direct impact of methamphetamine on isolated whole heart and single cardiomyocyte contractile function. Murine hearts and isolated cardiomyocytes from adult FVB mice were exposed to various concentrations of methamphetamine for 30 min prior to the assessment of mechanical function using a Langendroff apparatus and an IonOptix Myocam® system, respectively. Cardiac contractile properties analyzed included maximal velocity of left ventricular pressure development and decline (± dP/dt), peak shortening amplitude (PS), maximal velocity of shortening/relengthening (± dLdt), time-to-PS (TPS), time-to-90% relengthening (TR90), resting and electrically-stimulated increase of intracellular Ca2+ as well as intracellular Ca2+ decay. Our results revealed that acute methamphetamine exposure depressed ± dP/dt, PS and rise of intracellular Ca2+ without affecting ± dLdt, TPS, TR90, resting intracellular Ca2+ and intracellular Ca2+ decay. Furthermore, methamphetamine nullified the adrenergic agonist norepinephrine-elicited positive cardiomyocyte contractile response, including elevated PS, ± dLdt and shortened TR90 without affecting TPS. Western blot analysis showed unchanged expression of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a) and phospholamban, associated with upregulated Na+-Ca2+ exchanger levels following acute methamphetamine exposure. In addition, methamphetamine promoted overt cardiomyocyte protein damage evaluated by carbonyl formation. Taken together, these results demonstrate direct cardiac depressant effect of methamphetamine in myocardium and isolated cardiomyocytes, possibly associated with protein damage and dampened adrenergic response. PMID:19481142
Kanagasundaram, Nigel Suren
Acute kidney injury is common, dangerous and costly, affecting around one in five patients emergency admissions to hospital. Although survival decreases as disease worsens, it is now apparent that even modest degrees of dysfunction are not only associated with higher mortality but are an independent risk factor for death. This review focuses on the pathophysiology of acute kidney injury secondary to ischaemia - its commonest aetiology. The haemodynamic disturbances, endothelial injury, epithelial cell injury and immunological mechanisms underpinning its initiation and extension will be discussed along with the considerable and complex interplay between these factors that lead to an intense, pro-inflammatory state. Mechanisms of tubular recovery will be discussed but also the pathophysiology of abnormal repair with its direct consequences for long-term renal function. Finally, the concept of 'organ cross-talk' will be introduced as a potential explanation for the higher mortality observed with acute kidney injury that might be deemed modest in conventional biochemical terms.
Kulaylat, Afif N; Chesnut, Charles H; Patel, Sunil; Rocourt, Dorothy V; Clark, Joseph B
Nail gun injuries primarily occur in the extremities of adult males as a consequence of accidental occupational trauma. Such injury involving the thorax is much less common, and penetrating cardiac injury secondary to pneumatic nail gun discharge is rare. Although potentially lethal, most cases with cardiac trauma are survivable with expedient surgical intervention. Despite improvements in engineered safety mechanisms, the incidence of nail gun injuries has risen as use of the devices has increased. The widespread availability of these tools to nonprofessional consumers exposes a broader population to the potential hazards associated with these devices. We describe the presentation and successful management of the first reported case of penetrating cardiac nail gun injury in a young child.
Tapper, Elliot B; Bonder, Alan; Cardenas, Andres
Acute kidney injury in the setting of ascites and cirrhosis is a medical emergency characterized by significant morbidity and mortality. Clinicians other than gastroenterologists are often the front line against acute kidney injury for patients with ascites. Owing to the specifics of cirrhotic physiology, the treatment and prevention of acute kidney injury in the setting of ascites has unique features, widespread knowledge of which will benefit our patients with cirrhosis. Early detection and treatment of infection, maximization of cardiac output, and avoidance of medications that limit cardiorenal adaptations to arterial underfilling are part of a multipronged strategy to protect the renal function of our patients with cirrhosis and ascites.
Kukreja, Rakesh C; Yin, Chang; Salloum, Fadi N
MicroRNAs (miRNAs) have emerged as a novel class of endogenous, small, noncoding RNAs that negatively regulate gene expression via degradation or translational inhibition of their target mRNAs. Over 700 miRNAs have been identified and sequenced in humans, and the number of miRNA genes is estimated at more than 1000. Individual miRNA is functionally important as a transcription factor because it has the ability to regulate the expression of multiple genes through binding to its target with imperfect or perfect complement. In the heart, miRNAs have been involved in several clinical scenarios, such as ischemia/reperfusion (I/R) injury and heart failure suggesting that regulation of their function could be used as a novel cardioprotective strategy. In particular, miRNA-1, miRNA-21, miRNA-24, miRNA-29, miRNA-92a, miRNA-126, miRNA-133, miRNA-320, miRNA-199a, miRNA-208, and miRNA-195 have been shown to be regulated after I/R injury. Because tissue miRNAs can be released into circulating blood, they also offer exciting new opportunities for developing sensitive biomarkers, including miRNA-1, miRNA-126, miR-208, and miRNA-499, for acute myocardial infarction and other cardiac diseases.
Onem, Gokhan; Baltalarli, Ahmet; Sungurtekin, Hulya; Evrengul, Harun; Ozcan, Ali Vefa; Kaya, Seyda; Sacar, Mustafa
Cardiac herniation and torsion is a rare condition associated with a high mortality rate. We present an unusual case of sudden cardiogenic shock that was caused by torsion and herniation of the heart after an operation for a penetrating cardiac injury. The patient was successfully treated by urgent surgical intervention. PMID:17215988
Jawa, Randeep S; Anillo, Sergio; Kulaylat, Mahmoud N
Transfusion-related acute lung injury (TRALI) refers to a clinical syndrome of acute lung injury that occurs in a temporal relationship with the transfusion of blood products. Because of the difficulty in making its diagnosis, TRALI is often underreported. Three not necessarily mutually exclusive hypotheses have been described to explain its etiogenesis: antibody mediated, non-antibody mediated, and two hit mechanisms. Treatment is primarily supportive and includes supplemental oxygen. Diuretics are generally not indicated, as hypovolemia should be avoided. Compared with many other forms of acute lung injury, including the acute respiratory distress syndrome, TRALI is generally transient, reverses spontaneously, and carries a better prognosis. A variety of prevention strategies have been proposed, ranging from restrictive transfusion strategies to using plasma derived only from males.
Farha, Khalid Abou; AbouFarha, Ramy; Bolt, Marc
Background The acute impact of tobacco smoking on the cardiac hemodynamic parameters and its pathological implication in the process of arterial atherosclerosis need further exploration. This investigation was purposed to assess the acute impact of tobacco smoke on blood pressure and cardiac hemodynamic parameters. Methods Using an Ultrasonic Cardiac Output Monitor, and DINAMAP Pro 400 Series V2 blood pressure monitor, several cardiac hemodynamic parameters and the blood pressure were assessed in 14 smokers, 11 females and 3 males, at 2 time points, before and after smoking of one cigarette. Data, in terms of ratio of the means and 95% confidence interval were analyzed using ANOVA. Results Single-subject design in which the subject has served as his/her own control has been used. Tobacco smoking led to statistically significant acute increase in the means of all hemodynamic parameters, except for heart rate in female subjects, as compared to the means obtained before smoking. Conclusions Cigarette smoking induces acute non-physiologic alteration in cardiac outflow forces, exposing the aortic valve and arch to mechanical injury that might be implicated in initiating and promoting the process of aortic arch atherosclerosis and associated pathological lesions.
Sawyer, E. K.; Anderson, J. R.
Occupational medicine physicians frequently are presented with requests by employers to determine the work-relatedness of medical illnesses or injuries. Occasionally, this involves a sudden onset of acute epididymitis in the male employee after strenuous activity in the workplace. Because the vast majority of acute epididymitis cases have an underlying sexually transmitted disease component, this poses a real dilemma for the consulting physician. This article discusses the etiology and pathogenesis of acute epididymitis along with its epidemiologic significance and reviews workers' compensation and its possible legal interpretation when acute epididymitis occurs at the worksite. PMID:8691501
Young, Robert W
Inflammatory lung injury is an inevitable consequence of cardiac surgery with cardiopulmonary bypass. The lungs are particularly susceptible to the effects of the systemic inflammatory response to cardiopulmonary bypass. This insult is further exacerbated by a pulmonary ischemia-reperfusion injury after termination of bypass. Older patients and those with pre-existing lung disease will clearly be less tolerant of any lung injury and more likely to develop respiratory failure in the postoperative period. A requirement for prolonged ventilation has implications for morbidity, mortality, and cost of treatment. This review contains a summary of recent interventions and changes of practice that may reduce inflammatory lung injury after cardiac surgery. The review also focuses on a number of general aspects of perioperative management, which may exacerbate such injury, if performed poorly.
Walker, Vyvyca J.; Agarwal, Anupam
Summary Iron is an essential metal involved in several major cellular processes required to maintain life. Because of iron’s ability to cause oxidative damage, its transport, metabolism, and storage is strictly controlled in the body, especially in the small intestine, liver, and kidney. Iron plays a major role in acute kidney injury and has been a target for therapeutic intervention. However, the therapies that have been effective in animal models of acute kidney injury have not been successful in human beings. Targeting iron trafficking via ferritin, ferroportin, or hepcidin may offer new insights. This review focuses on the biology of iron, particularly in the kidney, and its implications in acute kidney injury. PMID:27085736
Walker, Vyvyca J; Agarwal, Anupam
Iron is an essential metal involved in several major cellular processes required to maintain life. Because of iron's ability to cause oxidative damage, its transport, metabolism, and storage is strictly controlled in the body, especially in the small intestine, liver, and kidney. Iron plays a major role in acute kidney injury and has been a target for therapeutic intervention. However, the therapies that have been effective in animal models of acute kidney injury have not been successful in human beings. Targeting iron trafficking via ferritin, ferroportin, or hepcidin may offer new insights. This review focuses on the biology of iron, particularly in the kidney, and its implications in acute kidney injury. Copyright © 2016. Published by Elsevier Inc.
Chow, T K; Bracker, M D; Patrick, K
We questioned members of 2 southern California off-road bicycling organizations about injuries associated with the use of all-terrain bicycles. Cyclists were asked about riding and safety habits, the kind(s) of injury sustained with their most recent accident and whether they sought medical treatment, and the circumstances of the accident. Of 459 mailed surveys, 268 (58.4%) were returned. Respondents (82.8% of whom were male) ranged in age from 14 to 68 years. Of these, 225 (84%) had been injured while riding all-terrain bicycles, 51% in the past year. Although most injuries were characterized as minor, 26% required professional medical care, and 4.4% of those injured were admitted to hospital. Extremity injuries--abrasions, lacerations, contusions--occurred in 201 (90%) cyclists with 27 (12%) sustaining a fracture or dislocation. High levels of helmet use (88%) may explain the low occurrence of head and neck trauma (12%). Frequent riding and riding on paved terrain were associated with increased severity of injury, although most accidents--197 (87.6%)--occurred off paved roads. These results suggest that, compared with regular bicyclists, all-terrain cyclists have more, but not necessarily more severe, injuries. Clinicians and emergency medical personnel should be aware that the increasing popularity of off-road cycling may change the frequency and nature of bicycling injuries. PMID:8212679
Cho, Seong; Lee, Yu-Ji; Kim, Sung-Rok
The purpose of this study was to evaluate the efficacy, complications, and mortality rate associated with acute peritoneal dialysis (PD) in patients with acute kidney injury (AKI). A total of 75 patients who were treated at Samsung Changwon Hospital between February 2005 and March 2016 were included in the study sample. The outcomes included in-hospital survival, renal recovery, metabolic and fluid control rates, and technical success rates. Refractory heart failure was the most frequent cause of acute PD (49.3%), followed by hepatic failure (20.0%), septic shock (14.7%), acute pancreatitis (9.3%), and unknown causes (6.7%). The hospital survival of patients in the acute PD was 48.0%. Etiologies of acute kidney injury (AKI) (refractory heart failure, acute pancreatitis compared with hepatic failure, septic shock or miscellaneous causes), use of inotropes, use of a ventilator, and simplified acute physiology score (SAPS) II were associated with survival differences. Maintenance dialysis required after survival was high (80.1% [29/36]) due to AKI etiologies (heart or hepatic failures). Metabolic and fluid control rates were 77.3%. The technical success rate for acute PD was 93.3%. Acute PD remains a suitable treatment modality for patients with AKI in the era of continuous renal replacement therapy (CRRT). Nearly all patients who require dialysis can be dialyzed with acute PD without mechanical difficulties. This is particularly true in patients with refractory heart failure and acute pancreatitis who had a weak requirement for inotropes. Copyright © 2017 International Society for Peritoneal Dialysis.
The acute knee injury represents one of the most common reasons to visit a general practitioner or an emergency department in a hospital. The initial assessment of an acute knee injury usually is affected by severe swelling, pain and a significant lack of motion. Conventional radiographs in three planes may provide additional information to limit the differential diagnosis. A clinical re-evaluation after five to ten days usually allows proper functional testing and therefore correct diagnosis in the majority of cases can be made. With suspicious clinical findings, MRI may be helpful to evaluate ligamentous, meniscal and cartilaginous structures. Femoro-tibial knee dislocation represents the most harmful acute knee injury and needs to be further evaluated and treated in an adequate medical institution in every suspicious case. Rapid vascular diagnostic with (CT)-angiography is crucial. Behind a multi-ligament injury of the knee a spontaneously reduced dislocation may hide and proper neuro-vascular exam therefore is mandatory in every patient. When fracture, blocking and major instability can be excluded at initial assessment, there is usually no need for any acute surgical intervention and initial conservative treatment may be conducted on an out-patient basis for most of the patients. Priority of surgical treatment depends on the injury pattern and delayed intervention with a pre-habilitative phase may be beneficial for certain pathologies.
Biswas, Hirak; Longmore, Gregory D.
Hypoxic injury to the heart results in cardiac fibrosis that leads to cardiac dysfunction and heart failure. SNAIL1 is a zinc finger transcription factor implicated in fibrosis following organ injury and cancer. To determine if the action of SNAIL1 contributed to cardiac fibrosis following hypoxic injury, we used an endogenous SNAIL1 bioluminescence reporter mice, and SNAIL1 knockout mouse models. Here we report that SNAIL1 expression is upregulated in the infarcted heart, especially in the myofibroblasts. Utilizing primary cardiac fibroblasts in ex vivo cultures we find that pro-fibrotic factors and collagen I increase SNAIL1 protein level. SNAIL1 is required in cardiac fibroblasts for the adoption of myofibroblast fate, collagen I expression and expression of fibrosis-related genes. Taken together this data suggests that SNAIL1 expression is induced in the cardiac fibroblasts after hypoxic injury and contributes to myofibroblast phenotype and a fibrotic scar formation. Resultant collagen deposition in the scar can maintain elevated SNAIL1 expression in the myofibroblasts and help propagate fibrosis. PMID:27706205
Wilson, Michelle; Staniforth, Andrew; Till, Richard; das Nair, Roshan; Vesey, Patrick
This exploratory study aimed to investigate the psychosocial outcomes for cardiac arrest survivors and explore if there is a greater impact on psychosocial outcome for individuals experiencing anoxic brain injury as a result of the cardiac arrest. Self-report measures were used to compare the quality of life, social functioning and symptoms of anxiety, depression and post-traumatic stress of individuals with and without anoxic brain injury. Secondary measures of subjective memory and executive difficulties were also used. Fifty-six participants (27 with anoxia, 29 without anoxia) took part in the study between six months and four years after experiencing cardiac arrest. A MANOVA identified a significant difference between the two groups, with the anoxia group reporting more psychosocial difficulties. They reported more social functioning difficulties and more anxiety, depression and post-traumatic stress symptoms. There was, however, no significant difference in self-reported quality of life between the two groups. As the first known study to compare psychosocial outcomes for cardiac arrest survivors experiencing anoxic brain injury with those without anoxia, the current results suggest that cardiac arrest survivors with subsequent acquired brain injury experience more psychosocial difficulties. This could be due to a combination of neuropsychological, social and psychological factors. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Gotzhein, Frauke; Escher, Felicitas; Blankenberg, Stefan; Westermann, Dirk
Background. Infection with Coxsackievirus B3 induces myocarditis. We aimed to compare the acute and chronic phases of viral myocarditis to identify the immediate effects of cardiac inflammation as well as the long-term effects after resolved inflammation on cardiac fibrosis and consequently on cardiac function. Material and Methods. We infected C57BL/6J mice with Coxsackievirus B3 and determined the hemodynamic function 7 as well as 28 days after infection. Subsequently, we analyzed viral burden and viral replication in the cardiac tissue as well as the expression of cytokines and matrix proteins. Furthermore, cardiac fibroblasts were infected with virus to investigate if viral infection alone induces profibrotic signaling. Results. Severe cardiac inflammation was determined and cardiac fibrosis was consistently colocalized with inflammation during the acute phase of myocarditis. Declined cardiac inflammation but no significantly improved hemodynamic function was observed 28 days after infection. Interestingly, cardiac fibrosis declined to basal levels as well. Both cardiac inflammation and fibrosis were reversible, whereas the hemodynamic function remains impaired after healed viral myocarditis in C57BL/6J mice. PMID:28352641
Filipowicz, Ewa; Staszków, Monika
Acute kidney injury (AKI) in obstetrics may be caused by the same disorders that are observed in the general population or may be specific for a pregnancy such as: preeclampsia, HELLP syndrome or acute fatty liver of pregnancy. The renal changes may be only temporary, and resolve within a few weeks postpartum, or may become irreversible leading to a progression of chronic kidney disease (CKD). In the article the most important pregnancy related syndromes associated with AKI have been shortly reviewed.
Lazzeri, Chiara; Picariello, Claudio; Dini, Carlotta Sorini; Gensini, Gian Franco; Valente, Serafina
Hyperlactataemia is commonly used as a diagnostic and prognostic tool in intensive care settings. Recent studies documented that serial lactate measurements over time (or lactate clearance), may be clinically more reliable than lactate absolute value for risk stratification in different pathological conditions. While the negative prognostic role of hyperlactataemia in several critical ill diseases (such as sepsis and trauma) is well established, data in patients with acute cardiac conditions (i.e. acute coronary syndromes) are scarce and controversial. The present paper provides an overview of the current available evidence on the clinical role of lactic acid levels and lactate clearance in acute cardiac settings (acute coronary syndromes, cardiogenic shock, cardiac surgery), focusing on its prognostic role. PMID:24062898
Seifert, Frank; Kallmünzer, Bernd; Gutjahr, Isabell; Breuer, Lorenz; Winder, Klemens; Kaschka, Iris; Kloska, Stephan; Doerfler, Arnd; Hilz, Max-Josef; Schwab, Stefan; Köhrmann, Martin
Neurocardiological interactions can cause severe cardiac arrhythmias in patients with acute ischemic stroke. The relationship between the lesion location in the brain and the occurrence of cardiac arrhythmias is still discussed controversially. The aim of the present study was to correlate the lesion location with the occurrence of cardiac arrhythmias in patients with acute ischemic stroke. Cardiac arrhythmias were systematically assessed in patients with acute ischemic stroke during the first 72 h after admission to a monitored stroke unit. Voxel-based lesion-symptom mapping (VLSM) was used to correlate the lesion location with the occurrence of clinically relevant severe arrhythmias. Overall 150 patients, 56 with right-hemispheric and 94 patients with a left-hemispheric lesion, were eligible to be included in the VLSM study. Severe cardiac arrhythmias were present in 49 of these 150 patients (32.7%). We found a significant association (FDR correction, q < 0.05) between lesions in the right insular, right frontal and right parietal cortex as well as the right amygdala, basal ganglia and thalamus and the occurrence of cardiac arrhythmias. Because left- and right-hemispheric lesions were analyzed separately, the significant findings rely on the 56 patients with right-hemispheric lesions. The data indicate that these areas are involved in central autonomic processing and that right-hemispheric lesions located to these areas are associated with an elevated risk for severe cardiac arrhythmias.
Ziegler, Tilman; Horstkotte, Melanie; Lange, Philipp; Ng, Judy; Bongiovanni, Dario; Hinkel, Rabea; Laugwitz, Karl-Ludwig; Sperandio, Markus; Horstkotte, Jan; Kupatt, Christian
Advanced glycation end-products (AGEs) interact with their receptor RAGE, leading to an inflammatory state. We investigated the role of RAGE in postischaemic leukocyte adhesion after myocardial infarction and its effect on postischaemic myocardial function. Wildtype (WT), ICAM-1-/-, RAGE-/- or ICAM-1/RAGE-/- mice underwent 20 minutes (min) of LAD-occlusion followed by 15 min of reperfusion. We applied in vivo fluorescence microscopy visualising Rhodamine-6G labelled leukocytes. To differentiate between endothelial and leukocyte RAGE, we generated bone marrow chimeric mice. Invasive hemodynamic measurements were performed in mice undergoing 45 min of myocardial ischaemia (via LAD-occlusion) followed by 24 hours of reperfusion. Left-ventricular developed pressure (LVDP) was assessed by insertion of a millar-tip catheter into the left ventricle. In the acute model of myocardial ischaemia, leukocyte retention (WT 68 ± 4 cells/hpf) was significantly reduced in ICAM-1-/- (40 ± 3 cells/hpf) and RAGE-/- mice (38 ± 4 cells/hpf). ICAM-1/RAGE-/- mice displayed an additive reduction of leukocyte retention (ICAM-1/RAGE-/- 15 ± 3 cells/hpf). Ly-6G+ neutrophil were predominantly reduced in ICAM-1/RAGE-/- hearts (28 %), whereas Ly-6C+ proinflammatory monocytes decreased to a lesser extent (55 %). Interestingly, PMN recruitment was not affected in chimeric mice with RAGE deficiency in BM cells (WT mice reconstituted with ICAM-1/RAGE-/- BM: 55 ± 4 cells/hpf) while in mice with global RAGE deficiency (ICAM-1/RAGE-/- mice reconstituted with ICAM-1/RAGE-/- BM) leucocyte retention was significantly reduced (13 ± 1 cells/hpf), similar to non-transplanted ICAM/RAGE-/- mice. Furthermore, postischaemic LVDP increased in ICAM-1/RAGE-/- animals (98 ± 4 mmHg vs 86 ± 4 mmHg in WT mice). In conclusion, combined deficiency of ICAM-1 and RAGE reduces leukocyte influx into infarcted myocardium and improves LV function during the acute phase after myocardial ischaemia and reperfusion
Pressly, Jeffrey D; Park, Frank
Ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury leading to an induction of oxidative stress, cellular dysfunction, and loss of renal function. DNA damage, including oxidative base modifications and physical DNA strand breaks, is a consequence of renal IRI. Like many other organs in the body, a redundant and highly conserved set of endogenous repair pathways have evolved to selectively recognize the various types of cellular DNA damage and combat its negative effects on cell viability. Severe damage to the DNA, however, can trigger cell death and elimination of the injured tubular epithelial cells. In this minireview, we summarize the state of the current field of DNA damage and repair in the kidney and provide some expected and, in some cases, unexpected effects of IRI on DNA damage and repair in the kidney. These findings may be applicable to other forms of acute kidney injury and could provide new opportunities for renal research.
Kanchan, Tanuj; Menezes, Ritesh G; Sirohi, Parmendra
The present photocase illustrates the possible mechanism of direct cardiac injuries from broken sharp jagged fractured ends of ribs in blunt force trauma to the chest in run over traffic mishaps. We propose that the projecting fractured ends of the ribs penetrate the underlying thoracic organs due to the transient phenomenon of deformation of chest cavity under pressure in run over traffic mishaps.
Jing, Zehao; Wang, Zhuorun; Li, Xiujie; Li, Xintao; Cao, Tingting; Bi, Yue; Zhou, Jicheng; Chen, Xu; Yu, Deqin; Zhu, Liang; Li, Shuzhuang
Quercetin is an important dietary flavonoid present in fruits and vegetables and has attracted attention because of its anti-inflammatory and anti-oxidative properties. Inflammation and oxidative stress play important roles in posttraumatic cardiomyocyte apoptosis, which contributes to secondary cardiac dysfunction. This study investigates the protective effect of quercetin on trauma-induced secondary cardiac injury and the mechanisms involved. Widely accepted nonlethal mechanical trauma models were established. In vivo, cardiomyocyte apoptosis and cardiac dysfunction in rats were assessed using TUNEL staining and a biological mechanic experiment system. In vitro, cell viability, tumour necrosis factor-α (TNF-α), reactive oxygen species (ROS) and [Ca2+]i of H9c2 cells were detected using an MTT assay, ELISA, and 2′,7′-dichlorofluorescin diacetate and fluo-4 acetoxymethyl ester assays respectively. Quercetin pretreatment (20 mg/kg i.p.; 0.5 h before trauma) significantly improved posttraumatic cardiomyocyte apoptosis and cardiac dysfunction. Pretreatment with quercetin (20 μM; 24 h before trauma plasma addition) significantly attenuated trauma-induced viability decreases, TNF-α increases, ROS overproduction and [Ca2+]i overload in H9c2 cells. In conclusion, quercetin may reverse posttraumatic cardiac dysfunction by reducing cardiomyocyte apoptosis through the suppression of TNF-α increases, ROS overproduction and Ca2+ overload in cardiomyocytes, representing a potential preventive approach for the treatment of secondary cardiac injury after mechanical trauma. PMID:27470932
Nagahara, Hidetake; Yamamoto, Aihiro; Seno, Takahiro; Obayashi, Hiroshi; Kida, Takashi; Nakabayashi, Amane; Kukida, Yuji; Fujioka, Kazuki; Fujii, Wataru; Murakami, Ken; Kohno, Masataka; Kawahito, Yutaka
Allograft inflammatory factor-1 (AIF-1) is a protein expressed by macrophages infiltrating the area around the coronary arteries of rats with an ectopic cardiac allograft. Some studies have shown that expression of AIF-1 increased in a mouse model of trinitrobenzene sulfonic acid-induced acute colitis and in acute cellular rejection of human cardiac allografts. These results suggest that AIF-1 is related to acute inflammation. The current study used bleomycin-induced acute lung injury to analyze the expression of AIF-1 and to examine its function in acute lung injury. Results showed that AIF-1 was significantly expressed in lung macrophages and increased in bronchoalveolar lavage fluid from mice with bleomycin-induced acute lung injury in comparison to control mice. Recombinant AIF-1 increased the production of IL-6 and TNF-α from RAW264.7 (a mouse macrophage cell line) and primary lung fibroblasts, and it also increased the production of KC (CXCL1) from lung fibroblasts. These results suggest that AIF-1 plays an important role in the mechanism underlying acute lung injury.
Eichenbaum, Kenneth D; Neustein, Steven M
In this review, the authors discussed criteria for diagnosing ALI; incidence, etiology, preoperative risk factors, intraoperative management, risk-reduction strategies, treatment, and prognosis. The anesthesiologist needs to maintain an index of suspicion for ALI in the perioperative period of thoracic surgery, particularly after lung resection on the right side. Acute hypoxemia, imaging analysis for diffuse infiltrates, and detecting a noncardiogenic origin for pulmonary edema are important hallmarks of acute lung injury. Conservative intraoperative fluid administration of neutral to slightly negative fluid balance over the postoperative first week can reduce the number of ventilator days. Fluid management may be optimized with the assistance of new imaging techniques, and the anesthesiologist should monitor for transfusion-related lung injuries. Small tidal volumes of 6 mL/kg and low plateau pressures of < or =30 cmH2O may reduce organ and systemic failure. PEEP may improve oxygenation and increases organ failure-free days but has not shown a mortality benefit. The optimal mode of ventilation has not been shown in perioperative studies. Permissive hypercapnia may be needed in order to reduce lung injury from positive-pressure ventilation. NO is not recommended as a treatment. Strategies such as bronchodilation, smoking cessation, steroids, and recruitment maneuvers are unproven to benefit mortality although symptomatically they often have been shown to help ALI patients. Further studies to isolate biomarkers active in the acute setting of lung injury and pharmacologic agents to inhibit inflammatory intermediates may help improve management of this complex disease.
Cereda, Maurizio; Xin, Yi; Meeder, Natalie; Zeng, Johnathan; Jiang, YunQing; Hamedani, Hooman; Profka, Harrilla; Kadlecek, Stephen; Clapp, Justin; Deshpande, Charuhas G.; Wu, Jue; Gee, James C.; Kavanagh, Brian P.; Rizi, Rahim R.
Background Mechanical ventilation worsens acute respiratory distress syndrome (ARDS), but this secondary ‘ventilator-associated’ injury is variable and difficult to predict. We aimed to visualize the propagation of such ventilator-induced injury, in the presence (and absence) of a primary underlying lung injury, and to determine the predictors of propagation. Methods Anesthetized rats (n=20) received acid aspiration (HCl) followed by ventilation with moderate tidal volume (VT). In animals surviving ventilation for at least two hours, propagation of injury was quantified using serial computed tomography (CT). Baseline lung status was assessed by oxygenation, lung weight, and lung strain (VT/expiratory lung volume). Separate groups of rats without HCl aspiration were ventilated with large (n=10) or moderate (n=6) VT. Results In 15 rats surviving longer than two hours, CT opacities spread outwards from the initial site of injury. Propagation was associated with higher baseline strain (propagation vs. no propagation, mean ± SD: 1.52 ± 0.13 vs. 1.16 ± 0.20, p<0.01), but similar oxygenation and lung weight. Propagation did not occur where baseline strain <1.29. In healthy animals, large VT caused injury that was propagated inwards from the lung periphery; in the absence of preexisting injury, propagation did not occur where strain was <2.0. Conclusions Compared with healthy lungs, underlying injury causes propagation to occur at a lower strain threshold and, it originates at the site of injury; this suggests that tissue around the primary lesion is more sensitive. Understanding how injury is propagated may ultimately facilitate a more individualized monitoring or management. PMID:26536308
Donnino, Michael W; Liu, Xiaowen; Andersen, Lars W; Rittenberger, Jon C; Abella, Benjamin S; Gaieski, David F; Ornato, Joseph P; Gazmuri, Raúl J; Grossestreuer, Anne V; Cocchi, Michael N; Abbate, Antonio; Uber, Amy; Clore, John; Peberdy, Mary Anne; Callaway, Clifton W
Mitochondrial injury post-cardiac arrest has been described in pre-clinical settings but the extent to which this injury occurs in humans remains largely unknown. We hypothesized that increased levels of mitochondrial biomarkers would be associated with mortality and neurological morbidity in post-cardiac arrest subjects. We performed a prospective multicenter study of post-cardiac arrest subjects. Inclusion criteria were comatose adults who suffered an out-of-hospital cardiac arrest. Mitochondrial biomarkers were measured at 0, 12, 24, 36 and 48h after return of spontaneous circulation as well as in healthy controls. Out of 111 subjects enrolled, 102 had evaluable samples at 0h. Cardiac arrest subjects had higher baseline cytochrome c levels compared to controls (2.18ng/mL [0.74, 7.74] vs. 0.16ng/mL [0.03, 0.91], p<0.001), and subjects who died had higher 0h cytochrome c levels compared to survivors (3.66ng/mL [1.40, 14.9] vs. 1.27ng/mL [0.16, 2.37], p<0.001). There were significantly higher Ribonuclease P (RNaseP) (3.3 [1.2, 5.7] vs. 1.2 [0.8, 1.2], p<0.001) and Beta-2microglobulin (B2M) (12.0 [1.0, 22.9], vs. 0.6 [0.6, 1.3], p<0.001) levels in cardiac arrest subjects at baseline compared to the control subjects. There were no differences between survivors and non-survivors for mitochondrial DNA, nuclear DNA, or cell free DNA. Cytochrome c was increased in post- cardiac arrest subjects compared to controls, and in post-cardiac arrest non-survivors compared to survivors. Nuclear DNA and cell free DNA was increased in plasma of post-cardiac arrest subjects. There were no differences in mitochondrial DNA, nuclear DNA, or cell free DNA between survivors and non-survivors. Mitochondrial injury markers showed mixed results in the post-cardiac arrest period. Future research needs to investigate these differences. Copyright © 2017 Elsevier B.V. All rights reserved.
Hanschen, Marc; Kanz, Karl-Georg; Kirchhoff, Chlodwig; Khalil, Philipe N.; Wierer, Matthias; van Griensven, Martijn; Laugwitz, Karl-Ludwig; Biberthaler, Peter; Lefering, Rolf; Huber-Wagner, Stefan
Background Blunt cardiac injury is a rare trauma entity. Here, we sought to evaluate the relevance and prognostic significance of blunt cardiac injury in severely injured patients. Methods In a retrospective multicentre study, using data collected from 47,580 patients enrolled to TraumaRegister DGU (1993-2009), characteristics of trauma, prehospital / hospital trauma management, and outcome analysis were correlated to the severity of blunt cardiac injury. The severity of cardiac injury was assessed according to the abbreviated injury score (AIS score 1-6), the revised injury severity score (RISC) allowed comparison of expected outcome with injury severity-dependent outcome. N = 1.090 had blunt cardiac trauma (AIS 1-6) (2.3% of patients). Results Predictors of blunt cardiac injury could be identified. Sternal fractures indicate a high risk of the presence of blunt cardiac injury (AIS 0 [control]: 3.0%; AIS 1: 19.3%; AIS 2-6: 19.1%). The overall mortality rate was 13.9%, minor cardiac injury (AIS 1) and severe cardiac injury (AIS 2-6) are associated with higher rates. Severe blunt cardiac injury (AIS 4 and AIS 5-6) is associated with a higher mortality (OR 2.79 and 4.89, respectively) as compared to the predicted average mortality (OR 2.49) of the study collective. Conclusion Multiple injured patients with blunt cardiac trauma are at high risk to be underestimated. Careful evaluation of trauma patients is able to predict the presence of blunt cardiac injury. The severity of blunt cardiac injury needs to be stratified according to the AIS score, as the patients’ outcome is dependent on the severity of cardiac injury. PMID:26136126
Yu, Liming; Fan, Chongxi; Li, Zhi; Zhang, Jian; Xue, Xiaodong; Xu, Yinli; Zhao, Guolong; Yang, Yang; Wang, Huishan
Stress hyperglycemia is commonly observed in patients suffering from ischemic heart disease. It not only worsens cardiovascular prognosis but also attenuates the efficacies of various cardioprotective agents. This study aimed to investigate the protective effect of melatonin against myocardial ischemia-reperfusion (MI/R) injury in acute hyperglycemic state with a focus on Notch1/Hes1/Akt signaling and intracellular thioredoxin (Trx) system. Sprague Dawley rats were subjected to MI/R surgery and high-glucose (HG, 500 g/L) infusion (4 mL/kg/h) to induce temporary hyperglycemia. Rats were treated with or without melatonin (10 mg/kg/d) during the operation. Furthermore, HG (33 mmol/L)-incubated H9c2 cardiomyoblasts were treated in the presence or absence of luzindole (a competitive melatonin receptor antagonist), DAPT (a γ-secretase inhibitor), LY294002 (a PI3-kinase/Akt inhibitor), or thioredoxin-interacting protein (Txnip) adenoviral vectors. We found that acute hyperglycemia aggravated MI/R injury by suppressing Notch1/Hes1/Akt signaling and intracellular Trx activity. Melatonin treatment effectively ameliorated MI/R injury by reducing infarct size, myocardial apoptosis, and oxidative stress. Moreover, melatonin also markedly enhanced Notch1/Hes1/Akt signaling and rescued intracellular Trx system by upregulating Notch1, N1ICD, Hes1, and p-Akt expressions, increasing Trx activity, and downregulating Txnip expression. However, these effects were blunted by luzindole, DAPT, or LY294002. Additionally, Txnip overexpression not only decreased Trx activity, but also attenuated the cytoprotective effect of melatonin. We conclude that impaired Notch1 signaling aggravates MI/R injury in acute hyperglycemic state. Melatonin rescues Trx system by reducing Txnip expression via Notch1/Hes1/Akt signaling in a membrane receptor-dependent manner. Its role as a prophylactic/therapeutic drug deserves further clinical study. © 2016 John Wiley & Sons A/S. Published by John Wiley
Nicolaidis, S C; Hildreth, D H; Lichtman, D M
Distal radioulnar joint injuries can occur in isolation or in association with distal radius fractures, Galeazzi fractures, Essex-Lopresti injuries, and both-bone forearm fractures. The authors have classified DRUJ/TFCC injuries into stable, partially unstable (subluxation), and unstable (dislocation) patterns based on the injured structures and clinical findings. Clinical findings and plain radiographs are usually sufficient to diagnose the lesion, but axial CT scans are pathognomonic. Diagnostic arthroscopy is the next test of choice to visualize stable and partially unstable lesions. Stable injuries of the DRUJ/TFCC unresponsive to conservative measures require arthroscopic debridement of the TFCC tear, along with ulnar shortening if there is ulnar-positive variance. Partially unstable injuries, on the other hand, are treated with direct arthroscopic or open repair of the TFCC tear, once again, along with ulnar shortening if ulnar-positive variance is present. Unstable injuries include simple and complex DRUJ dislocations. A simple DRUJ dislocation is easily reducible but may be stable or unstable. In complex dislocation, reduction is not possible because there is soft tissue interposition or a significant tear. After the associated injury is dealt with, treatment for complex injuries requires exploration of the DRUJ, extraction of the interposed tissue, repair of the soft tissues, and open reduction and internal fixation of the ulnar styloid fracture (if present and displaced). The early recognition and appropriate treatment of an acute DRUJ injury are critical to avoid progression to a chronic DRUJ disorder, the treatment of which is much more difficult and much less satisfying.
van Breda, G. Fenna; Bongartz, Lennart G.; Zhuang, Wenqing; van Swelm, Rachel P.L.; Pertijs, Jeanne; Braam, Branko; Cramer, Maarten-Jan; Swinkels, Dorine W.; Doevendans, Pieter A.; Verhaar, Marianne C.; Masereeuw, Roos; Joles, Jaap A.; Gaillard, Carlo A.J.M.
Background Hepcidin regulates systemic iron homeostasis by downregulating the iron exporter ferroportin. Circulating hepcidin is mainly derived from the liver but hepcidin is also produced in the heart. We studied the differential and local regulation of hepcidin gene expression in response to myocardial infarction (MI) and/or chronic kidney disease (CKD). We hypothesized that cardiac hepcidin gene expression is induced by and regulated to severity of cardiac injury, either through direct (MI) or remote (CKD) stimuli, as well as through increased local iron content. Methods Nine weeks after subtotal nephrectomy (SNX) or sham surgery (CON), rats were subjected to coronary ligation (CL) or sham surgery to realize 4 groups: CON, SNX, CL and SNX + CL. In week 16, the gene expression of hepcidin, iron and damage markers in cardiac and liver tissues was assessed by quantitative polymerase chain reaction and ferritin protein expression was studied by immunohistochemistry. Results Cardiac hepcidin messenger RNA (mRNA) expression was increased 2-fold in CL (p = 0.03) and 3-fold in SNX (p = 0.01). Cardiac ferritin staining was not different among groups. Cardiac hepcidin mRNA expression correlated with mRNA expression levels of brain natriuretic peptide (β = 0.734, p < 0.001) and connective tissue growth factor (β = 0.431, p = 0.02). In contrast, liver hepcidin expression was unaffected by SNX and CL alone, while it had decreased 50% in SNX + CL (p < 0.05). Hepatic ferritin immunostaining was not different among groups. Conclusions Our data indicate differences in hepcidin regulation in liver and heart and suggest a role for injury rather than iron as the driving force for cardiac hepcidin expression in renocardiac failure. PMID:27771699
Willson, Douglas F.; Chess, Patricia R.; Notter, Robert H.
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
Grommes, Jochen; Soehnlein, Oliver
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.
Peck, Brandon W; Workeneh, Biruh; Kadikoy, Huseyin; Abdellatif, Abdul
Sodium hypochlorite (bleach) is commonly used as an irrigant during dental procedures as well as a topical antiseptic agent. Although it is generally safe when applied topically, reports of accidental injection of sodium hypochlorite into tissue have been reported. Local necrosis, pain and nerve damage have been described as a result of exposure, but sodium hypo-chlorite has never been implicated as a cause of an acute kidney injury (AKI). In this report, we describe the first case of accidental sodium hypochlorite injection into the infraorbital tissue during a dental procedure that precipitated the AKI. We speculate that oxidative species induced by sodium hypochlorite caused AKI secondary to the renal tubular injury, causing mild acute tubular necrosis.
Kuai, Qiyuan; Wang, Chunyan; Wang, Yanbing; Li, Weijing; Zhang, Gongqing; Qiao, Zhixin; He, Min; Wang, Xuanlin; Wang, Yu; Jiang, Xingwei; Su, Lihua; He, Yuezhong; Ren, Suping; Yu, Qun
A disturbance of energy metabolism reduces cardiac function in acute severe hemorrhagic patients. Alternatively, adequate energy supply reduces heart failure and increases survival. However, the approach to regulating energy metabolism conductive to vital organs is limited, and the underlying molecular mechanism remains unknown. This study assesses the ability of histone deacetylase inhibitors (HDACIs) to preserve cardiac energy metabolism during lethal hemorrhagic injury. In the lethally hemorrhagic rat and hypoxic myocardial cells, energy metabolism and heart function were well maintained following HDACI treatment, as evident by continuous ATP production with normal cardiac contraction. Valproic acid (VPA) regulated the energy metabolism of hemorrhagic heart by reducing lactate synthesis and protecting the mitochondrial ultrastructure and respiration, which were attributable to the inhibition of lactate dehydrogenase A activity and the increased myeloid cell leukemia-1 (mcl-1) gene expression, ultimately facilitating ATP production and consumption. MCL-1, the key target of VPA, mediated this cardioprotective effect under acute severe hemorrhage conditions. Our results suggest that HDACIs promote cardioprotection by improving energy metabolism during hemorrhagic injury and could therefore be an effective strategy to counteract this process in the clinical setting. PMID:27910887
Kuai, Qiyuan; Wang, Chunyan; Wang, Yanbing; Li, Weijing; Zhang, Gongqing; Qiao, Zhixin; He, Min; Wang, Xuanlin; Wang, Yu; Jiang, Xingwei; Su, Lihua; He, Yuezhong; Ren, Suping; Yu, Qun
A disturbance of energy metabolism reduces cardiac function in acute severe hemorrhagic patients. Alternatively, adequate energy supply reduces heart failure and increases survival. However, the approach to regulating energy metabolism conductive to vital organs is limited, and the underlying molecular mechanism remains unknown. This study assesses the ability of histone deacetylase inhibitors (HDACIs) to preserve cardiac energy metabolism during lethal hemorrhagic injury. In the lethally hemorrhagic rat and hypoxic myocardial cells, energy metabolism and heart function were well maintained following HDACI treatment, as evident by continuous ATP production with normal cardiac contraction. Valproic acid (VPA) regulated the energy metabolism of hemorrhagic heart by reducing lactate synthesis and protecting the mitochondrial ultrastructure and respiration, which were attributable to the inhibition of lactate dehydrogenase A activity and the increased myeloid cell leukemia-1 (mcl-1) gene expression, ultimately facilitating ATP production and consumption. MCL-1, the key target of VPA, mediated this cardioprotective effect under acute severe hemorrhage conditions. Our results suggest that HDACIs promote cardioprotection by improving energy metabolism during hemorrhagic injury and could therefore be an effective strategy to counteract this process in the clinical setting.
Zarbock, Alexander; Schmidt, Christoph; Van Aken, Hugo; Wempe, Carola; Martens, Sven; Zahn, Peter K; Wolf, Britta; Goebel, Ulrich; Schwer, Christian I; Rosenberger, Peter; Haeberle, Helene; Görlich, Dennis; Kellum, John A; Meersch, Melanie
No interventions have yet been identified to reduce the risk of acute kidney injury in the setting of cardiac surgery. To determine whether remote ischemic preconditioning reduces the rate and severity of acute kidney injury in patients undergoing cardiac surgery. In this multicenter trial, we enrolled 240 patients at high risk for acute kidney injury, as identified by a Cleveland Clinic Foundation score of 6 or higher, between August 2013 and June 2014 at 4 hospitals in Germany. We randomized them to receive remote ischemic preconditioning or sham remote ischemic preconditioning (control). All patients completed follow-up 30 days after surgery and were analyzed according to the intention-to-treat principle. Patients received either remote ischemic preconditioning (3 cycles of 5-minute ischemia and 5-minute reperfusion in one upper arm after induction of anesthesia) or sham remote ischemic preconditioning (control), both via blood pressure cuff inflation. The primary end point was the rate of acute kidney injury defined by Kidney Disease: Improving Global Outcomes criteria within the first 72 hours after cardiac surgery. Secondary end points included use of renal replacement therapy, duration of intensive care unit stay, occurrence of myocardial infarction and stroke, in-hospital and 30-day mortality, and change in acute kidney injury biomarkers. Acute kidney injury was significantly reduced with remote ischemic preconditioning (45 of 120 patients [37.5%]) compared with control (63 of 120 patients [52.5%]; absolute risk reduction, 15%; 95% CI, 2.56%-27.44%; P = .02). Fewer patients receiving remote ischemic preconditioning received renal replacement therapy (7 [5.8%] vs 19 [15.8%]; absolute risk reduction, 10%; 95% CI, 2.25%-17.75%; P = .01), and remote ischemic preconditioning reduced intensive care unit stay (3 days [interquartile range, 2-5]) vs 4 days (interquartile range, 2-7) (P = .04). There was no significant effect of remote ischemic
Oliveira, João Fernando Picollo; Burdmann, Emmanuel A.
Dengue is presently the most relevant viral infection transmitted by a mosquito bite that represents a major threat to public health worldwide. Acute kidney injury (AKI) is a serious and potentially lethal complication of this disease, and the actual incidence is unknown. In this review, we will assess the most relevant epidemiological and clinical data regarding dengue and the available evidence on the frequency, etiopathogenesis, outcomes and treatment of dengue-associated AKI. PMID:26613023
Aspirin is thought to be a relatively safe drug in adults. The association of aspirin and Reye syndrome in children is well documented. We report a 41-year-old female with pericarditis who was treated with high-dose aspirin and developed subsequent acute liver injury. After discontinuation of aspirin, liver enzyme elevation and right upper quadrant pain both resolved. We conclude that high-dose aspirin should be considered as a potentially hepatotoxic agent. PMID:26157904
In most patients, wasp stings cause local reactions and rarely anaphylaxis. Acute kidney injury and rhabdomyolysis are unusual complications of wasp stings. We report a case of acute kidney injury and rhabdomyolysis secondary to multiple wasp stings. A 55-year-old farmer developed multi organ dysfunction with acute kidney injury and rhabdomyolysis 3 days after he had sustained multiple wasp stings. The etiology of acute kidney injury is probably both rhabdomyolysis and acute tubular necrosis. He improved completely after hemodialysis and intensive care. PMID:25097363
Murray, Katie N.; Parry-Jones, Adrian R.; Allan, Stuart M.
Inflammation is the key host-defense response to infection and injury, yet also a major contributor to a diverse range of diseases, both peripheral and central in origin. Brain injury as a result of stroke or trauma is a leading cause of death and disability worldwide, yet there are no effective treatments, resulting in enormous social and economic costs. Increasing evidence, both preclinical and clinical, highlights inflammation as an important factor in stroke, both in determining outcome and as a contributor to risk. A number of inflammatory mediators have been proposed as key targets for intervention to reduce the burden of stroke, several reaching clinical trial, but as yet yielding no success. Many factors could explain these failures, including the lack of robust preclinical evidence and poorly designed clinical trials, in addition to the complex nature of the clinical condition. Lack of consideration in preclinical studies of associated co-morbidities prevalent in the clinical stroke population is now seen as an important omission in previous work. These co-morbidities (atherosclerosis, hypertension, diabetes, infection) have a strong inflammatory component, supporting the need for greater understanding of how inflammation contributes to acute brain injury. Interleukin (IL)-1 is the prototypical pro-inflammatory cytokine, first identified many years ago as the endogenous pyrogen. Research over the last 20 years or so reveals that IL-1 is an important mediator of neuronal injury and blocking the actions of IL-1 is beneficial in a number of experimental models of brain damage. Mechanisms underlying the actions of IL-1 in brain injury remain unclear, though increasing evidence indicates the cerebrovasculature as a key target. Recent literature supporting this and other aspects of how IL-1 and systemic inflammation in general contribute to acute brain injury are discussed in this review. PMID:25705177
Turk, Elisabeth E; Tsang, Yee-Wah; Champaneri, Anisha; Pueschel, Klaus; Byard, Roger W
Motor vehicle accidents contribute widely to population morbidity and mortality around the world, and cardiac injuries are a major factor determining outcome. Autopsy reports from 380 motor vehicle occupants who died in motor vehicle crashes in Adelaide, Australia, and Hamburg, Germany, over a 6-year period were reviewed, analysing the presence and type of cardiac injuries and their correlation with factors such as crash type, presence of seatbelt/airbag and vehicle speed as well as with the presence of other injuries which might predict the presence of cardiac injuries in a clinical setting. 21.1% had cardiac injuries identified macroscopically autopsy or histology. Cardiac injuries were the only cause of death or contributed to a fatal outcome in 76% of these cases. Sternal fractures and left-sided serial rib fractures were predictive of cardiac injury.
Moore, Lynne; Evans, David; Yanchar, Natalie L; Thakore, Jaimini; Stelfox, Henry Thomas; Hameed, Sayed Morad; Simons, Richard; Kortbeek, John; Clément, Julien; Lauzier, François; Turgeon, Alexis F
Acute care injury outcomes vary substantially across Canadian provinces and trauma centres. Our aim was to develop Canadian benchmarks to monitor mortality and hospital length of stay (LOS) for injury admissions. Benchmarks were derived using data from the Canadian National Trauma Registry on patients with major trauma admitted to any level I or II trauma centre in Canada and from the following patient subgroups: isolated traumatic brain injury (TBI), isolated thoracoabdominal injury, multisystem blunt injury, age 65 years or older. We assessed predictive validity using measures of discrimination and calibration, and performed sensitivity analyses to assess the impact of replacing analytically complex methods (multiple imputation, shrinkage estimates and flexible modelling) with simple models that can be implemented locally. The mortality risk adjustment model had excellent discrimination and calibration (area under the receiver operating characteristic curve 0.886, Hosmer-Lemeshow 36). The LOS risk-adjustment model predicted 29% of the variation in LOS. Overall, observed:expected ratios of mortality and mean LOS generated by an analytically simple model correlated strongly with those generated by analytically complex models (r > 0.95, κ on outliers > 0.90). We propose Canadian benchmarks that can be used to monitor quality of care in Canadian trauma centres using Excel (see the appendices, available at canjsurg.ca). The program can be implemented using local trauma registries, providing that at least 100 patients are available for analysis.
Yang, Jingzhen; Tibbetts, Abigail S.; Covassin, Tracey; Cheng, Gang; Nayar, Saloni; Heiden, Erin
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
Kossaify, Antoine; Garcia, Annie; Succar, Sami; Ibrahim, Antoine; Moussallem, Nicolas; Kossaify, Mikhael; Grollier, Gilles
Biomarkers in acute cardiac care are gaining increasing interest given their clinical benefits. This study is a review of the major conditions in acute cardiac care, with a focus on biomarkers for diagnostic and prognostic assessment. Through a PubMed search, 110 relevant articles were selected. The most commonly used cardiac biomarkers (cardiac troponin, natriuretic peptides, and C-reactive protein) are presented first, followed by a description of variable acute cardiac conditions with their relevant biomarkers. In addition to the conventional use of natriuretic peptides, cardiac troponin, and C-reactive protein, other biomarkers are outlined in variable critical conditions that may be related to acute cardiac illness. These include ST2 and chromogranin A in acute dyspnea and acute heart failure, matrix metalloproteinase in acute chest pain, heart-type fatty acid binding protein in acute coronary syndrome, CD40 ligand and interleukin-6 in acute myocardial infarction, blood ammonia and lactate in cardiac arrest, as well as tumor necrosis factor-alpha in atrial fibrillation. Endothelial dysfunction, oxidative stress and inflammation are involved in the physiopathology of most cardiac diseases, whether acute or chronic. In summary, natriuretic peptides, cardiac troponin, C-reactive protein are currently the most relevant biomarkers in acute cardiac care. Point-of-care testing and multi-markers use are essential for prompt diagnostic approach and tailored strategic management.
Kossaify, Antoine; Garcia, Annie; Succar, Sami; Ibrahim, Antoine; Moussallem, Nicolas; Kossaify, Mikhael; Grollier, Gilles
Biomarkers in acute cardiac care are gaining increasing interest given their clinical benefits. This study is a review of the major conditions in acute cardiac care, with a focus on biomarkers for diagnostic and prognostic assessment. Through a PubMed search, 110 relevant articles were selected. The most commonly used cardiac biomarkers (cardiac troponin, natriuretic peptides, and C-reactive protein) are presented first, followed by a description of variable acute cardiac conditions with their relevant biomarkers. In addition to the conventional use of natriuretic peptides, cardiac troponin, and C-reactive protein, other biomarkers are outlined in variable critical conditions that may be related to acute cardiac illness. These include ST2 and chromogranin A in acute dyspnea and acute heart failure, matrix metalloproteinase in acute chest pain, heart-type fatty acid binding protein in acute coronary syndrome, CD40 ligand and interleukin-6 in acute myocardial infarction, blood ammonia and lactate in cardiac arrest, as well as tumor necrosis factor-alpha in atrial fibrillation. Endothelial dysfunction, oxidative stress and inflammation are involved in the physiopathology of most cardiac diseases, whether acute or chronic. In summary, natriuretic peptides, cardiac troponin, C-reactive protein are currently the most relevant biomarkers in acute cardiac care. Point-of-care testing and multi-markers use are essential for prompt diagnostic approach and tailored strategic management. PMID:24046510
Long-term exposure to PM has been associated with cardiac injury in rats. The purpose of this study was to investigate if cardiac injury was due to soluble metals (i.e., zinc), insoluble PM, or pulmonary injury/inflammation. Male Wistar Kyoto rats (n=8) were exposed intratracheal...
Long-term exposure to PM has been associated with cardiac injury in rats. The purpose of this study was to investigate if cardiac injury was due to soluble metals (i.e., zinc), insoluble PM, or pulmonary injury/inflammation. Male Wistar Kyoto rats (n=8) were exposed intratracheal...
Halm, M A
Gastrointestinal problems, with an incidence of about 1%, may complicate the postoperative period after cardiovascular surgery, increasing morbidity, length of stay, and mortality. Several risk factors for the development of these complications, including preexisting conditions; advancing age; surgical procedure, especially valve, combined bypass/valve, emergency, reoperative, and aortic dissection repair; iatrogenic conditions; stress; ischemia; and postpump complications, have been identified in multiple research studies. Ischemia is the most significant of these risk factors after cardiovascular surgery. Mechanisms that have been implicated include longer cardiopulmonary bypass and aortic cross-clamp times and hypoperfusion states, especially if inotropic or intra-aortic balloon pump support is required. These risk factors have been linked to upper and lower gastrointestinal bleeding, paralytic ileus, intestinal ischemia, acute diverticulitis, acute cholecystitis, hepatic dysfunction, hyperamylasemia, and acute pancreatitis. Gastrointestinal bleeding accounts for almost half of all complications, followed by hepatic dysfunction, intestinal ischemia, and acute cholecystitis. Identification of these gastrointestinal complications may be difficult because manifestations may be masked by postoperative analgesia or not reported by patients because they are sedated or require prolonged mechanical ventilation. Furthermore, clinical manifestations may be nonspecific and not follow the "classic" clinical picture. Therefore, astute assessment skills are needed to recognize these problems in high-risk patients early in their clinical course. Such early recognition will prompt aggressive medical and/or surgical management and therefore improve patient outcomes for the cardiovascular surgical population.
Shank, C D; Walters, B C; Hadley, M N
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.
Russ, Kirk B.; Stevens, Todd M; Singal, Ashwani K.
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
Cisneros, Luis Natera; Reiriz, Juan Sarasquete
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.
Soong, Thing Rinda; Pathak, Arvind; Asano, Hiroshi; Fox-Talbot, Karen; Baldwin, William M
Background: Severed donor heart lymphatics are not anastomosed to recipient lymphatics in cardiac transplantation. We evaluated the effects of cellular infiltrates of T cells and macrophages on the morphology of lymphatics in heart grafts. Methods: Dark Agouti (DA) hearts were transplanted to Lewis or control DA rats on sub-therapeutic doses of cyclosporin. Transplants were examined by immunohistology and quantitative immunofluorescence microscopy using LYVE-1 as a lymphatic marker and CD8 and CD68 as markers for cellular infiltration at selected intervals from 1 to 8 weeks post-transplantation. Results: Allograft inner myocardial lymphatic density decreased by more than 30-fold at 1 week, and recovered to only 15% of the native level at 8 weeks post-transplantation. In contrast, allograft lymphatics in and near the epicardium showed no significant density decline, but increased in size by more than 5-fold at 2 weeks, and sustained about a 3-fold increase at 8 weeks post-transplantation. Lymphatic changes correlated temporally with the extent of T cell and macrophage infiltration in allografts, which peaked at 2-3 weeks post-transplantation. When grafts were retransplanted from allogeneic to isogeneic recipients at 3 weeks post-transplantation, inner lymphatic density returned close to native level within 2 weeks after retransplantation. Conclusions: This is the first characterization of regional and morphological effects of immunological responses on heart lymphatics after transplantation. Elimination of alloimmune responses produces rapid restoration of inner lymphatic vessels, suggesting that lymphatics injured during rejection can recover when rejection is reversed during the post-transplantation course. PMID:20118845
Stine, Jonathan G; Newton, Kelly; Vinayak, Ajeet G
Primary malignant tumors of the heart, specifically cardiac sarcomas, are rare and mainly diagnosed at autopsy. Acute Budd-Chiari syndrome is a recognized cause of acute liver failure and has been associated with several rare cardiac tumors: atrial myxoma, caval rhabdomyosarcoma, and primary cardiac adenocarcinoma. We present the first case of a fatal, highly differentiated cardiac synovial sarcoma that presented as acute liver failure from Budd-Chiari syndrome.
Eun, John C.; Moore, Ernest E.; Mauchley, David C.; Johnson, Chris A.; Meng, Xianzhong; Banerjee, Anirban; Wohlauer, Max V.; Zarini, Simona; Gijón, Miguel A.; Murphy, Robert C.
The cellular and biochemical mechanisms leading to acute lung injury and subsequent multiple organ failure are only partially understood. In order to study the potential role of eicosanoids, particularly leukotrienes, as possible mediators of acute lung injury, we used a murine experimental model of acute lung injury induced by hemorrhagic shock after blood removal via cardiac puncture. Neutrophil sequestration as shown by immunofluorescence, and protein leakage into the alveolar space, were measured as markers of injury. We used liquid chromatography coupled to tandem mass spectrometry to unequivocally identify several eicosanoids in the bronchoalveolar lavage fluid of experimental animals. MK886, a specific inhibitor of the 5-lipoxygenase pathway, as well as transgenic mice deficient in 5-lipoxygenase, were used to determine the role of this enzymatic pathway in this model. Leukotriene B4 and leukotriene C4 were consistently elevated in shock-treated mice compared to sham-treated mice. MK886 attenuated neutrophil infiltration and protein extravasation induced by hemorrhagic shock. 5-lipoxygenase-deficient mice showed reduced neutrophil infiltration and protein extravasation after shock treatment, indicating greatly reduced lung injury. These results support the hypothesis that 5-lipoxygenase, most likely through the generation of leukotrienes, plays an important role in the pathogenesis of acute lung injury induced by hemorrhagic shock in mice. This pathway could represent a new target for pharmacological intervention to reduce lung damage following severe primary injury. PMID:22392149
Vikrant, Sanjay; Verma, Balbir Singh
Envenomations by venomous lizards are rare. Monitor lizard bite-induced acute kidney injury (AKI) is a previously unreported complication in humans. A 55-year-old female was bitten on her right leg during farming activity by a monitor lizard (Varanus bengalensis). The patient experienced severe local pain and bleeding from the wound, coagulopathy, hemolysis, rhabdomyolysis, sepsis, and AKI. Patient was treated with supportive care and peritoneal dialysis but succumbed to a sudden cardiac arrest. Post mortem kidney biopsy revealed pigment induced-acute tubular injury. AKI after monitor lizard envenomation is caused by acute tubular injury in the setting of intravascular hemolysis, rhabdomyolysis and sepsis. Coagulopathy and direct nephrotoxicity may be the other contributory factors in causing AKI.
Stelter, Zachary; Strakova, Jana; Yellamilli, Amritha; Fischer, Kaleb; Sharpe, Katharine
Duchenne muscular dystrophy (DMD) is a disease of progressive destruction of striated muscle, resulting in muscle weakness with progressive respiratory and cardiac failure. Respiratory and cardiac disease are the leading causes of death in DMD patients. Previous studies have suggested an important link between cardiac dysfunction and hypoxia in the dystrophic heart; these studies aim to understand the mechanism underlying this connection. Here we demonstrate that anesthetized dystrophic mice display significant mortality following acute exposure to hypoxia. This increased mortality is associated with a significant metabolic acidosis, despite having significantly higher levels of arterial Po2. Chronic hypoxia does not result in mortality, but rather is characterized by marked cardiac fibrosis. Studies in isolated hearts reveal that the contractile function of dystrophic hearts is highly susceptible to short bouts of ischemia, but these hearts tolerate prolonged acidosis better than wild-type hearts, indicating an increased sensitivity of the dystrophic heart to hypoxia. Dystrophic hearts display decreased cardiac efficiency and oxygen extraction. Isolated dystrophic cardiomyocytes and hearts have normal levels of FCCP-induced oxygen consumption, and mitochondrial morphology and content are normal in the dystrophic heart. These studies demonstrate reductions in cardiac efficiency and oxygen extraction of the dystrophic heart. The underlying cause of this reduced oxygen extraction is not clear; however, the current studies suggest that large disruptions of mitochondrial respiratory function or coronary flow regulation are not responsible. This finding is significant, as hypoxia is a common and largely preventable component of DMD that may contribute to the progression of the cardiac disease in DMD patients. PMID:26851247
Stelter, Zachary; Strakova, Jana; Yellamilli, Amritha; Fischer, Kaleb; Sharpe, Katharine; Townsend, DeWayne
Duchenne muscular dystrophy (DMD) is a disease of progressive destruction of striated muscle, resulting in muscle weakness with progressive respiratory and cardiac failure. Respiratory and cardiac disease are the leading causes of death in DMD patients. Previous studies have suggested an important link between cardiac dysfunction and hypoxia in the dystrophic heart; these studies aim to understand the mechanism underlying this connection. Here we demonstrate that anesthetized dystrophic mice display significant mortality following acute exposure to hypoxia. This increased mortality is associated with a significant metabolic acidosis, despite having significantly higher levels of arterial Po2 Chronic hypoxia does not result in mortality, but rather is characterized by marked cardiac fibrosis. Studies in isolated hearts reveal that the contractile function of dystrophic hearts is highly susceptible to short bouts of ischemia, but these hearts tolerate prolonged acidosis better than wild-type hearts, indicating an increased sensitivity of the dystrophic heart to hypoxia. Dystrophic hearts display decreased cardiac efficiency and oxygen extraction. Isolated dystrophic cardiomyocytes and hearts have normal levels of FCCP-induced oxygen consumption, and mitochondrial morphology and content are normal in the dystrophic heart. These studies demonstrate reductions in cardiac efficiency and oxygen extraction of the dystrophic heart. The underlying cause of this reduced oxygen extraction is not clear; however, the current studies suggest that large disruptions of mitochondrial respiratory function or coronary flow regulation are not responsible. This finding is significant, as hypoxia is a common and largely preventable component of DMD that may contribute to the progression of the cardiac disease in DMD patients.
Porcel, José M
Pleural effusions are frequent in the context of acute idiopathic pericarditis and following pericardiotomy, but they have seldom been characterized. This review summarizes their most relevant clinical features. In acute idiopathic pericarditis, pleural effusions tend to be left-sided and, if bilateral, they are usually larger on the left. Less than 5% are unilateral right-sided. About 90% of the effusions occupy less than one-third of the hemithorax, and 99% meet Light's exudative criteria with a predominance of lymphocytes in three fourths of the cases. Although postcardiac injury syndrome (PCIS)-related effusions share similar characteristics, they present some differential features: more than 15% are unilateral on the right (except for Dressler syndrome), one-fourth opacify half or more of the hemithorax, and nearly two thirds are bloody. The combination of nonsteroidal anti-inflammatory drugs and colchicine, along with therapeutic thoracenteses for moderate-to-large effusions, is the mainstay treatment approach. The postoperative use of colchicine is also a reasonable option for preventing PCIS in patients who have undergone cardiac surgery. Pleural effusions because of pericardial diseases remain a clinical diagnosis. If unilateral right-sided, massive, or transudative effusions are seen, an alternative diagnosis to acute pericarditis should be considered.
Papasotiriou, Marios; Betsi, Grigoria; Tsironi, Maria; Assimakopoulos, Georgios
Rhabdomyolysis is usually caused by muscle injury, drugs or alcohol and presents with muscle weakness and pain. It is characterized by rise in serum creatine kinase, aminotransferases and electrolytes as well as myoglobinuria. Myoglobinuria may cause acute kidney injury by direct proximal tubule cytotoxicity, renal vasoconstriction, intraluminal cast formation and distal tubule obstruction. Muscle pain and weakness as well as vascular injury have been reported after acupuncture. We report a case of severe rhabdomyolysis and acute kidney injury after acupuncture sessions.
Di Siena, S; Gimmelli, R; Nori, S L; Barbagallo, F; Campolo, F; Dolci, S; Rossi, P; Venneri, M A; Giannetta, E; Gianfrilli, D; Feigenbaum, L; Lenzi, A; Naro, F; Cianflone, E; Mancuso, T; Torella, D; Isidori, A M; Pellegrini, M
The role of endogenous c-Kit receptor activation on cardiac cell homeostasis and repair remains largely unexplored. Transgenic mice carrying an activating point mutation (TgD814Y) in the kinase domain of the c-Kit gene were generated. c-KitTgD814Y receptor was expressed in the heart during embryonic development and postnatal life, in a similar timing and expression pattern to that of the endogenous gene, but not in the hematopoietic compartment allowing the study of a cardiac-specific phenotype. c-KitTgD814Y mutation produced a constitutive active c-Kit receptor in cardiac tissue and cells from transgenic mice as demonstrated by the increased phosphorylation of ERK1/2 and AKT, which are the main downstream molecular effectors of c-Kit receptor signaling. In adult transgenic hearts, cardiac morphology, size and total c-Kit+ cardiac cell number was not different compared with wt mice. However, when c-KitTgD814Y mice were subjected to transmural necrotic heart damage by cryoinjury (CI), all transgenic survived, compared with half of wt mice. In the sub-acute phase after CI, transgenic and wt mice showed similar heart damage. However, 9 days after CI, transgenic mice exhibited an increased number of c-Kit+CD31+ endothelial progenitor cells surrounding the necrotic area. At later follow-up, a consistent reduction of fibrotic area, increased capillary density and increased cardiomyocyte replenishment rate (as established by BrdU incorporation) were observed in transgenic compared with wt mice. Consistently, CD45−c-Kit+ cardiac stem cells isolated from transgenic c-KitTgD814Y mice showed an enhanced endothelial and cardiomyocyte differentiation potential compared with cells isolated from the wt. Constitutive activation of c-Kit receptor in mice is associated with an increased cardiac myogenic and vasculogenic reparative potential after injury, with a significant improvement of survival. PMID:27468693
Malka, Assaf; Ertracht, Offir; Bachner-Hinenzon, Noa; Reiter, Irina; Binah, Ofer
Following acute myocardial infarction (MI), early and successful reperfusion is the most effective strategy for reducing infarct size and improving the clinical outcome. However, immediate restoration of blood flow to the ischemic zone results in myocardial damage, defined as "reperfusion-injury". Whereas we previously reported that TVP1022 (the S-isomer of rasagiline, FDA-approved anti-Parkinson drug) decreased infarct size 24 h post ischemia reperfusion (I/R) in rats, in this study we investigated the chronic cardioprotective efficacy of TVP1022 14 days post-I/R. To simulate the clinical settings of acute MI followed by reperfusion therapy, we employed a rat model of left anterior descending artery occlusion for 30 min followed by reperfusion and a follow-up for 14 days. TVP1022 was initially administered postocclusion-prereperfusion, followed by chronic daily administrations. Cardiac performance and remodeling were evaluated using customary and advanced echocardiographic methods, hemodynamic measurements by Millar Mikro-Tip(®) catheter, and histopathological techniques. TVP1022 administration markedly decreased the remodeling process as illustrated by attenuation of left ventricular enlargement and cardiac hypertrophy (both at the whole heart and the cellular level). Furthermore, TVP1022 inhibited cardiac fibrosis and reduced ventricular BNP levels. Functionally, TVP1022 treatment preserved cardiac wall motion. Specifically, the echocardiographic and most of the direct hemodynamic measures were pronouncedly improved by TVP1022. Collectively, these findings indicate that TVP1022 provides prominent cardioprotection against I/R injury and post-MI remodeling in this I/R model.
Jamuar, Saumya S; Newton, Stephanie A; Prabhu, Sanjay P; Hecht, Leah; Costas, Karen C; Wessel, Ann E; Harris, David J; Anselm, Irina; Berry, Gerard T
An 8-½ year old boy with glutaric aciduria type I (GA1) and chronic dystonia presented with severe rhabdomyolysis in association with a febrile illness. His clinical course was complicated by acute renal failure, cardiac arrest and hypoxic ischemic encephalopathy. As acute neurological decompensation is typically not seen in patients with GA1 beyond early childhood, this case report serves as an important reminder that patients with GA1 and status dystonicus may be at risk for acute life-threatening rhabdomyolysis, renal failure and further neurological injury at any age. Copyright © 2012 Elsevier Inc. All rights reserved.
Jamal, Faisal; Prabhakar, Sharma
Synthetic cannabinoids (SCB) are a family of chemicals that bind to cannabinoid receptors and cause psychoactive effects. Over the past few years, they have been increasingly used for recreational purposes, especially by young adults, and have been reported to have many adverse effects. Acute kidney injury (AKI) has been recently reported; the pathophysiology of SCB-induced AKI is unknown. We report three cases of AKI in the setting of SCB use. The peak serum creatinine levels ranged from 3.0 to 5.7 mg/dL; one patient required hemodialysis. SCB can induce AKI. PMID:26424946
Campbell, G Adam; Hu, Daniel; Okusa, Mark D
Acute kidney injury (AKI) is a frequent and significant complication of cancer and cancer therapy. Cancer patients frequently encounter risk factors for AKI including older age, CKD, prerenal conditions, sepsis, exposure to nephrotoxins, and obstructive physiology. AKI can also be secondary to paraneoplastic conditions, including glomerulonephritis and microangiopathic processes. This complication can have significant consequences, including effects on patients' ability to continue to receive therapy for their malignancy. This review will serve to summarize potential etiologies of AKI that present in patients with cancer as well as to highlight specific patient populations, such as the critically ill cancer patient.
Rosner, Mitchell H
Most patients who develop acute kidney injury (AKI) are older than 65 years. Specific structural and functional changes that occur in the aging kidney predispose the elderly patient to AKI. This risk is further compounded by comorbid conditions, polypharmacy, and the need for invasive procedures. When AKI does occur, it is associated with significant morbidity and mortality. Although morbidity and mortality increases with advancing age, many elderly patients can survive AKI and do well. Thus, decision making should be thoughtful and individualized, and not dependent on age. Whenever possible, preventive approaches should be pursued to lessen the burden of AKI.
Makris, Konstantinos; Spanou, Loukia
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
Nwoko, Rosemary; Plecas, Darko; Garovic, Vesna D
Acute kidney injury (AKI) is costly and is associated with increased mortality and morbidity. An understanding of the renal physiologic changes that occur during pregnancy is essential for proper evaluation, diagnosis, and management of AKI. As in the general population, AKI can occur from prerenal, intrinsic, and post-renal causes. Major causes of pre-renal azotemia include hyperemesis gravidarum and uterine hemorrhage in the setting of placental abruption. Intrinsic etiologies include infections from acute pyelonephritis and septic abortion, bilateral cortical necrosis, and acute tubular necrosis. Particular attention should be paid to specific conditions that lead to AKI during the second and third trimesters, such as preeclampsia, HELLP syndrome, acute fatty liver of pregnancy, and TTP-HUS. For each of these disorders, delivery of the fetus is the recommended therapeutic option, with additional therapies indicated for each specific disease entity. An understanding of the various etiologies of AKI in the pregnant patient is key to the appropriate clinical management, prevention of adverse maternal outcomes, and safe delivery of the fetus. In pregnant women with pre-existing kidney disease, the degree of renal dysfunction is the major determining factor of pregnancy outcomes, which may further be complicated by a prior history of hypertension.
Cowley, Alice; Dobson, Laura; Kurian, John; Saunderson, Christopher
Isolated myocardial involvement in tuberculosis is exceedingly rare but there are reports it can present with sudden cardiac death, atrioventricular block, ventricular arrhythmias or congestive cardiac failure. We report the case of a 33-year-old male, of South Asian descent, who presented with chest pain, shortness of breath and an abnormal ECG. The patient had no significant past medical history and coronary angiogram showed no evidence of coronary artery disease. Of note, the patient had recently been discharged from a local district hospital with an episode of myocarditis. The patient was found to be severely hypoxic with evidence of severe biventricular failure on echocardiography. Computed tomography of the chest demonstrated hilar lymphadenopathy, and the differential diagnosis was thought to be tuberculosis or sarcoidosis. A TB Quantiferon gold test performed at the district hospital was positive; however, fine needle aspiration was negative for acid-fast bacilli. Despite aggressive diuresis, the patient became increasingly hypoxic and suffered a cardiac arrest. Post-mortem confirmed a diagnosis of myocardial tuberculosis - a rare case of acute decompensated heart failure. Tuberculosis myocarditis is a rare diagnosis but should be considered in at risk individuals presenting with acute fulminant myocarditis.Cardiac failure can occur even in the absence of disseminated tubercular disease.TB myocarditis is not just a disease of the immunocompromised.Definitive diagnosis of cardiac tuberculosis during life requires a myocardial biopsy.Echocardiography is a vital tool for the assessment of cardiac function, filling pressures and fluid status in the critically unwell patient. © 2017 The authors.
Yap, Steven C.; Lee, H. Thomas
Purpose of Review Acute Kidney Injury (AKI) is a major clinical problem without effective therapy. Development of AKI among hospitalized patients drastically increases mortality, and morbidity. With increases in complex surgical procedures together with a growing elderly population, the incidence of AKI is rising. Renal adenosine receptor (AR) manipulation may have great therapeutic potential in mitigating AKI. In this review, we discuss renal AR biology and potential clinical therapies for AKI. Recent Findings The 4 AR subtypes (A1AR, A2AAR, A2BAR and A3AR) have diverse effects on the kidney. The pathophysiology of AKI may dictate the specific AR subtype activation needed to produce renal protection. The A1AR activation in renal tubules and endothelial cells produces beneficial effects against ischemia and reperfusion (IR) injury by modulating metabolic demand, decreasing necrosis, apoptosis and inflammation. The A2AAR protects against AKI by modulating leukocyte-mediated renal and systemic inflammation whereas the A2BAR activation protects by direct activation of renal parenchymal ARs. In contrast, the A1AR antagonism may play a protective role in nephrotoxic AKI and radiocontrast induced nephropathy by reversing vascular constriction and inducing naturesis and diuresis. Furthermore, as the A3AR-activation exacerbates apoptosis and tissue damage due to renal IR, selective A3AR antagonism may hold promise to attenuate renal IR injury. Finally, renal A1AR activation also protects against renal endothelial dysfunction caused by hepatic IR injury. Summary Despite the current lack of therapies for the treatment and prevention of AKI, recent research suggests that modulation of renal ARs holds promise in treating AKI and extrarenal injury. PMID:22080856
Magalhães, Patrícia Andréa da Fonseca; de Brito, Teresinha Silva; Freire, Rosemayre Souza; da Silva, Moisés Tolentino Bento; dos Santos, Armênio Aguiar; Vale, Mariana Lima; de Menezes, Dalgimar Beserra; Martins, Alice Maria Costa; Libório, Alexandre Braga
Ischemia/reperfusion (I/R) injury and metabolic acidosis (MA) are two critical conditions that may simultaneously occur in clinical practice. The result of this combination can be harmful to the kidneys, but this issue has not been thoroughly investigated. The present study evaluated the influence of low systemic pH on various parameters of kidney function in rats that were subjected to an experimental model of renal I/R injury. Metabolic acidosis was induced in male Wistar rats by ingesting ammonium chloride (NH4Cl) in tap water, beginning 2 days before ischemic insult and maintained during the entire study. Ischemia/reperfusion was induced by clamping both renal arteries for 45 min, followed by 48 h of reperfusion. Four groups were studied: control (subjected to sham surgery, n=8), I/R (n=8), metabolic acidosis (MA; 0.28 M NH4Cl solution and sham surgery, n=6), and MA+I/R (0.28 M NH4Cl solution plus I/R, n=9). Compared with I/R rats, MA+I/R rats exhibited higher mortality (50 vs. 11%, p=0.03), significant reductions of blood pH, plasma bicarbonate (pBic), and standard base excess (SBE), with a severe decline in the glomerular filtration rate and tubular function. Microscopic tubular injury signals were detected. Immunofluorescence revealed that the combination of MA and I/R markedly increased nuclear factor κB (NF-κB) and heme-oxygenase 1 (HO-1), but it did not interfere with the decrease in endothelial nitric oxide synthase (eNOS) expression that was caused by I/R injury. Acute ischemic kidney injury is exacerbated by acidic conditions. Copyright © 2016 Elsevier Inc. All rights reserved.
Caruso, Deborah; Carter, William E; Cifu, David X; Carne, William
Survivability characteristics after cardiopulmonary resuscitation in the population with spinal cord injury (SCI) are unclear but may be useful for advanced care planning discussions with patients. Retrospective evaluation from records of all SCI patients over 10 yr at a Department of Veterans Affairs medical center who experienced in-hospital cardiac arrest was performed. Demographic data and other common measurements were recorded. Thirty-six male subjects were identified, and only two patients survived to discharge (5.5% survival rate), both of whom were admitted for nonacute issues and were asymptomatic shortly before the cardiac arrest. The mean age at the time of cardiopulmonary arrest was 62.4 yr, with a mean time from cardiac arrest to death of 3.02 d. No significant demographic parameters were identified. Overall, SCI likely portends worse outcome for acutely ill patients in the situation of a cardiac arrest. Conclusions are limited by sample size.
We have recently demonstrated that PM containing water-soluble zinc may cause cardiac injury following pulmonary exposure. To investigate if pulmonary zinc exposure causes systemic metal imbalance and direct cardiac effects, we intratracheally (IT) instilled male Wistar Kyoto (WK...
We have recently demonstrated that PM containing water-soluble zinc may cause cardiac injury following pulmonary exposure. To investigate if pulmonary zinc exposure causes systemic metal imbalance and direct cardiac effects, we intratracheally (IT) instilled male Wistar Kyoto (WK...
Quindry, John C; Hamilton, Karyn L
Cardiovascular disease (CVD), including ischemia reperfusion (IR) injury, remains a major cause of morbidity and mortality in industrialized nations. Ongoing research is aimed at uncovering therapeutic interventions against IR injury. Regular exercise participation is recognized as an important lifestyle intervention in the prevention and treatment of CVD and IR injury. More recent understanding reveals that moderate intensity aerobic exercise is also an important experimental model for understanding the cellular mechanisms of cardioprotection against IR injury. An important discovery in this regard was the observation that one-to-several days of exercise will attenuate IR injury. This phenomenon has been observed in young and old hearts of both sexes. Due to the short time course of exercise induced protection, IR injury prevention must be mediated by acute biochemical alterations within the myocardium. Research over the last decade reveals that redundant mechanisms account for exercise induced cardioprotection against IR. While much is now known about exercise preconditioning against IR injury, many questions remain. Perhaps most pressing, is what mechanisms mediate cardioprotection in aged hearts and what sex-dependent differences exist. Given that that exercise preconditioning is a polygenic effect, it is likely that multiple mediators of exercise induced cardioprotection have yet to be uncovered. Also unknown, is whether post translational modifications due to exercise are responsible for IR injury prevention. This review will provide an overview the major mechanisms of IR injury and exercise preconditioning. The discussion highlights many promising avenues for further research and describes how exercise preconditioning may continue to be an important scientific paradigm in the translation of cardioprotection research to the clinic. PMID:23909636
Hägglund, Martin; Waldén, Markus
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.
Moledina, Dennis G; Hall, Isaac E; Thiessen-Philbrook, Heather; Reese, Peter P; Weng, Francis L; Schröppel, Bernd; Doshi, Mona D; Wilson, F Perry; Coca, Steven G; Parikh, Chirag R
The diagnosis of acute kidney injury (AKI), which is currently defined as an increase in serum creatinine (Scr) concentration, provides little information on the condition's actual cause. To improve phenotyping of AKI, many urinary biomarkers of tubular injury are being investigated. Because AKI cases are not frequently biopsied, the diagnostic accuracy of concentrations of Scr and urinary biomarkers for histologic acute tubular injury is unknown. Cross-sectional analysis from multicenter prospective cohort. Hospitalized deceased kidney donors on whom kidney biopsies were performed at the time of organ procurement for histologic evaluation. (1) AKI diagnosed by change in Scr concentration during donor hospitalization and (2) concentrations of urinary biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], liver-type fatty acid-binding protein [L-FABP], interleukin 18 [IL-18], and kidney injury molecule 1 [KIM-1]) measured at organ procurement. Histologic acute tubular injury. Of 581 donors, 98 (17%) had mild acute tubular injury and 57 (10%) had severe acute tubular injury. Overall, Scr-based AKI had poor diagnostic performance for identifying histologic acute tubular injury and 49% of donors with severe acute tubular injury did not have AKI. The area under the receiver operating characteristic curve (AUROC) of change in Scr concentration for diagnosing severe acute tubular injury was 0.58 (95% CI, 0.49-0.67) and for any acute tubular injury was 0.52 (95% CI, 0.45-0.58). Compared with Scr concentration, NGAL concentration demonstrated higher AUROC for diagnosing both severe acute tubular injury (0.67; 95% CI, 0.60-0.74; P=0.03) and any acute tubular injury (0.60; 95% CI, 0.55-0.66; P=0.005). In donors who did not have Scr-based AKI, NGAL concentrations were higher with increasing severities of acute tubular injury (subclinical AKI). However, compared with Scr concentration, AUROCs for acute tubular injury diagnosis were not significantly higher for urinary L
Whitaker, Ryan M.; Stallons, L. Jay; Kneff, Joshua E.; Alge, Joseph L.; Harmon, Jennifer L.; Rahn, Jennifer J.; Arthur, John M.; Beeson, Craig C.; Chan, Sherine L.; Schnellmann, Rick G.
Recent studies show the importance of mitochondrial dysfunction in the initiation and progression of acute kidney injury (AKI). However, no biomarkers exist linking renal injury to mitochondrial function and integrity. To this end, we evaluated urinary mitochondrial DNA (UmtDNA) as a biomarker of renal injury and function in humans with AKI following cardiac surgery. mtDNA was isolated from the urine of patients following cardiac surgery and quantified by qPCR. Patients were stratified into no AKI, stable AKI and progressive AKI groups based on Acute Kidney Injury Network (AKIN) staging. UmtDNA was elevated in progressive AKI patients, and was associated with progression of patients with AKI at collection to higher AKIN stages. To evaluate the relationship of UmtDNA to measures of renal mitochondrial integrity in AKI, mice were subjected to sham surgery or varying degrees of ischemia followed by 24 hours of reperfusion. UmtDNA increased in mice after 10-15 minutes of ischemia and positively correlated with ischemia time. Furthermore, UmtDNA was predictive of AKI in the mouse model. Finally, UmtDNA levels were negatively correlated with renal cortical mtDNA and mitochondrial gene expression. These translational studies demonstrate that UmtDNA is associated with recovery from AKI following cardiac surgery by serving as an indicator of mitochondrial integrity. Thus, UmtDNA may serve as valuable biomarker for the development of mitochondrial targeted therapies in AKI. PMID:26287315
Munnur, Ravi Kiran; Cameron, James D.; Ko, Brian S.; Meredith, Ian T.
Coronary computed tomographic angiography (CCTA) is a robust non-invasive method to assess coronary artery disease (CAD). Qualitative and quantitative assessment of atherosclerotic coronary stenosis with CCTA has been favourably compared with invasive coronary angiography (ICA) and intravascular ultrasound (IVUS). Importantly, it allows the study of preclinical stages of atherosclerotic disease, may help improve risk stratification and monitor the progressive course of the disease. The diagnostic accuracy of CCTA in the assessment of coronary artery bypass grafts (CABG) is excellent and the constantly improving technology is making the evaluation of stents feasible. Novel techniques are being developed to assess the functional significance of coronary stenosis. The excellent negative predictive value of CCTA in ruling out disease enables early and safe discharge of patients with suspected acute coronary syndromes (ACS) in the Emergency Department (ED). In addition, CCTA is useful in predicting clinical outcomes based on the extent of coronary atherosclerosis and also based on individual plaque characteristics such as low attenuation plaque (LAP), positive remodelling and spotty calcification. In this article, we review the role of CCTA in the detection of coronary atherosclerosis in native vessels, stented vessels, calcified arteries and grafts; the assessment of plaque progression, evaluation of chest pain in the ED, assessment of functional significance of stenosis and the prognostic significance of CCTA. PMID:25610801
Barnason, Susan; Steinke, Elaine; Mosack, Victoria; Wright, David W
: The purpose of this study was to examine the differences between outpatient cardiac rehabilitation (CR) and acute care nurses perceived barriers and clinical practices of providing sexual counseling for myocardial infarction patients. : A nonexperimental descriptive, comparative research design with convenience sampling was used to survey CR and acute care nurses using the Survey of Sexuality Related Nursing Practice-Myocardial Infarction questionnaire. : A total of 320 nurses (81 CR nurses, 239 acute care nurses), in midwestern states completed the survey. Using ANCOVA analyses with age, work status, and education level as covariates, findings demonstrated CR nurses had significantly higher levels of role responsibility (F[4, 315] = 5.4, P < .05) and implementation of sexual counseling in clinical practice (F[4, 315] = 9.1, P < .0001). : Findings from this study further elucidate the influence of practice settings on the actual implementation of patient education and counseling of cardiac patients regarding sexual functioning. Outpatient CR nurses reported fewer barriers and reported higher rates of implementing sexual counseling into their practice. These findings support the importance of CR referral to provide both physical and psychosocial rehabilitation after a cardiac event. Findings bring to light the need to address the gap in practice to meet the perceived unmet needs of patients regarding their concerns of sexual functioning while hospitalized and for those patients who may not enroll in CR after hospital discharge.
Pozzato, Marco; Ferrari, Fiorenza; Livigni, Sergio; Quarello, Francesco
Acute kidney injury (AKI) occurs in 5-45% of critically ill patients, and renal replacement therapy (RRT) is required in 4-10% of patients with AKI. AKI has long been considered to be hemodynamic damage from low blood flow resulting in shock, and efforts have been made to prevent and cure it by increasing the renal blood flow and improving the cardiac output and perfusion pressure. In recent years, new experimental studies on patients with septic AKI have shown that the renal blood flow remains unaltered or even increases in septic shock. An important mechanism in the pathophysiology of sepsis and septic shock appears to be apoptosis rather than ischemic necrosis. The type of treatment as well as the dose and timing of initiation of RRT seem to have strategic importance in the recovery of AKI in patients admitted to the ICU. In critically ill (often postsurgical and septic) patients with acute renal failure the use of new anticoagulation strategies has permitted to perform treatments for a sufficient number of hours to achieve the correct level of purification by minimizing the downtime and the bleeding risk. In our center the use of protocols for different methods and different types of anticoagulants has simplified the treatment of all patients with AKI and septic shock admitted to the ICU.
Orts, M; Ribera, J M; Calatrava, A; Larrouse, E; Catalán, R; Navarro, J T; Millá, F; Feliu, E
Although cardiac infiltration is common in advanced stage of acute leukaemia, it is not usually diagnosed at life and it is extremely rare for it to become pseudotumoral. A 25-years-old patient with an acute monoblastic leukaemia who had a leukaemic infiltration which affected the main part of the left ventricle at the time of diagnosis, is referred. The heart infiltration was detected by a two dimension echocardiography. In spite of a massive infiltration, heart failure was not present and the left ventricle's ejection fraction was 50%. Even though chemotherapy was administered, the patient died four days after diagnosis due to septic shock of respiratory origin. The most relevant autopsy finding was a widespread pseudotumoral infiltration of the left ventricle, the back side of the right ventricle and the interventricular wall. The pseudotumoral infiltration of the heart by acute leukaemia is uncommon and must be differentiated from granulocytic sarcoma. The usefulness of the different diagnostic procedures is discussed.
Liang, Shao; Aiqun, Ma; Figtree, Gemma; Ping, Zhang
Acute hypoxia and reoxygenation injury, as a common environmental stress condition, is a basic condition of most pathophysiological processes. It has been approve that autophagy and oxidant stress could contribute to acute hypoxia and reoxygenation injury. This study is aimed to examine the effect of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) silence on cell injury with acute hypoxia and reoxygenation injury by autophagy and antioxidant stress pathway. GAPDH expression was silenced by siRNA in H9C2 cardiomyoblasts with acute hypoxia and reoxygenation injury. Autophagy was detected by western blot for autophagy proteins and monodansylcadaverine (MDC) staining for acidic substances. Pro-apoptosis protein and flow cytometry were used to assess cell apoptosis and death and intracellular adenosine triphosphate (ATP) relative concentration was measured. Oxidant stress was assessed by measuring 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA), thiobarbituric acid reactive substances (TBARS), glutathione (GSH) and super oxide dismutase (SOD). In this study, GAPDH-silence enhanced autophagy in H9C2 cells with acute hypoxia and reoxygenation injury, decreased oxidant stress and increased antioxidant pathways; and reduced cell apoptosis and death. However, GAPDH-silence had no significant effect on cell energy. GAPDH pre-silence by siRNA reduces H9C2 cell death occurring via autophagy and anti-oxidative stress pathway in acute hypoxia and reoxygenation injury. This study enriches the understanding of GAPDH pathophysiology role, and provides potential new therapeutic targets for cardiac disease states characterized by oxidative stress. Copyright © 2015 Elsevier B.V. All rights reserved.
Deng, Ruoxian; Xiong, Wei; Jia, Xiaofeng
Reliable prognostic methods for cerebral functional outcome of post cardiac-arrest (CA) patients are necessary, especially since therapeutic hypothermia (TH) as a standard treatment. Traditional neurophysiological prognostic indicators, such as clinical examination and chemical biomarkers, may result in indecisive outcome predictions and do not directly reflect neuronal activity, though they have remained the mainstay of clinical prognosis. The most recent advances in electrophysiological methods—electroencephalography (EEG) pattern, evoked potential (EP) and cellular electrophysiological measurement—were developed to complement these deficiencies, and will be examined in this review article. EEG pattern (reactivity and continuity) provides real-time and accurate information for early-stage (particularly in the first 24 h) hypoxic-ischemic (HI) brain injury patients with high sensitivity. However, the signal is easily affected by external stimuli, thus the measurements of EP should be combined with EEG background to validate the predicted neurologic functional result. Cellular electrophysiology, such as multi-unit activity (MUA) and local field potentials (LFP), has strong potential for improving prognostication and therapy by offering additional neurophysiologic information to understand the underlying mechanisms of therapeutic methods. Electrophysiology provides reliable and precise prognostication on both global and cellular levels secondary to cerebral injury in cardiac arrest patients treated with TH. PMID:26528970
McMaster, Jason; Desai, Pathik J.; Desai, Sapan S.; Kuy, SreyRam; Mata, Maggy; Cooper, Jamie
The treatment of isolated sternal fractures (ISF) throughout the world is heterogeneous. This study aimed to identify the incidence, morbidity, and mortality associated with isolated fractures of the sternum and describe current practice for diagnosis and management of ISF and cardiac injury at a level I trauma center in the UK. A retrospective cohort study of adult patients (>16 years) with ISF presenting from 2006 to 2010 was conducted. Eighty-eight patients with ISF were identified. Most patients (88%, 77) were admitted to hospital with 66% (58) of them discharged within 48 hours. Two (2%) patients had an ER EKG with abnormality but both resolved to normal sinus rhythm within 6 hours of follow-up. Serum CEs were drawn from 55 (63%) patients with only 2 (2%) having a rise in serum troponin >0.04; however, in both of these patients troponin quickly normalized. Six (7%) patients underwent echocardiograms without significant findings. In all 88 patients with ISF, no cases of clinically significant cardiac injury were identified. Patients presenting with an isolated sternal fracture with no changes on EKG or chest X-ray do not warrant an admission to hospital and may be discharged from the ER. PMID:24653859
Roberts, George H
Transfusion is an inevitable event in the life of many individuals. Transfusion medicine personnel attempt to provide blood products that will result in a safe and harmless transfusion. However, this is not always possible since no laboratory test gives totally accurate and reliable results all the time and testing in routine transfusion services is devoted primarily to the identification of red blood cell problems. Thus, when patients are transfused, several possible adverse effects may occur in the transfused patient even though quality testing indicates no potential problem. These adverse events include infectious complications, hemolytic reactions, anaphylaxis, urticaria, circulatory overload, transfusion-associated graft-versus-host disease, chills and fever, immunomodulation, and transfusion-related acute lung injury (TRALI).
Approximately one person in 5,000 will experience an episode of transfusion-related acute lung injury (TRALI) in conjunction with the transfusion of whole blood or blood components. Its hallmarks include hypoxemia, dyspnea, fever, hypotension, and bilateral pulmonary edema (noncardiogenic). The mortality for reported cases is 16.3%. The incidence and mortality may be even higher than estimated because of under-recognition and under-reporting. Although TRALI was identified as a clinical entity in the 1980s, a lack of consensus regarding a definition was present until 2004. An exact cause has yet to be identified; however, there are two theories regarding the etiology: the "antibody" and the "two-hit" theories. These theories involve both donor and recipient factors. Further education and research are needed to assist in the development of strategies for the prevention and treatment of TRALI.
Goldstein, Stuart L
Fluid management in critical illness has undergone extensive reevaluation in the past decade. Since a significant percentage of critically ill patients develop acute kidney injury (AKI), optimal fluid management is even more paramount to prevent the ill effects of either underhydration or overhydration. The concepts of early goal-directed fluid therapy (EGDT) and conservative late fluid management permeate current clinical research, and the independent association between fluid accumulation and mortality has been repeatedly demonstrated. A number of prospective randomized trials are planned to provide an adequately powered assessment of the effect of EGDT or earlier renal replacement therapy initiation in patients with, or at risk for AKI. The aim of this analytical review is to use existing clinical and physiological studies to support a 3-phase model of fluid management in the critically ill patient with AKI. © The Author(s) 2012.
Goldstein, Stuart L
The present article will review the current state of our understanding of nephrotoxic medication-associated acute kidney injury (AKI) and provide strategies to reduce its impact. Nephrotoxic medications contribute to a substantial proportion of AKI in hospitalized patients. The previous perspective of nephrotoxic medication-associated AKI as a nonmodifiable necessary evil of providing appropriate therapy to ill patients had led to an incomplete understanding of its epidemiology and provided little impetus to reduce its occurrence. Recent work on understanding specific combinations, thresholds for nephrotoxic burden and systematic kidney function assessment had mitigated, and even in some cases reduced, nephrotoxic AKI rates and severity. Current initiatives are underway to further refine specific nephrotoxic medication AKI risk via novel urinary biomarkers and genetic susceptibility.
Liu, Wen-wu; Han, Cui-hong; Zhang, Pei-xi; Zheng, Juan; Liu, Kan; Sun, Xue-jun
Hyperoxic acute lung injury (HALI) refers to the damage to the lungs secondary to exposure to elevated oxygen partial pressure. HALI has been a concern in clinical practice with the development of deep diving and the use of normobaric as well as hyperbaric oxygen in clinical practice. Although the pathogenesis of HALI has been extensively studied, the findings are still controversial. Nitric oxide (NO) is an intercellular messenger and has been considered as a signaling molecule involved in many physiological and pathological processes. Although the role of NO in the occurrence and development of pulmonary diseases including HALI has been extensively studied, the findings on the role of NO in HALI are conflicting. Moreover, inhalation of NO has been approved as a therapeutic strategy for several diseases. In this paper, we briefly summarize the role of NO in the pathogenesis of HALI and the therapeutic potential of inhaled NO in HALI. PMID:27867474
Moore, Elizabeth; Bellomo, Rinaldo
Erythropoietin (EPO) is a 30.4 kDa glycoprotein produced by the kidney, and is mostly well-known for its physiological function in regulating red blood cell production in the bone marrow. Accumulating evidence, however, suggests that EPO has additional organ protective effects, which may be useful in the prevention or treatment of acute kidney injury. These protective mechanisms are multifactorial in nature and include inhibition of apoptotic cell death, stimulation of cellular regeneration, inhibition of deleterious pathways, and promotion of recovery.In this article, we review the physiology of EPO, assess previous work that supports the role of EPO as a general tissue protective agent, and explain the mechanisms by which it may achieve this tissue protective effect. We then focus on experimental and clinical data that suggest that EPO has a kidney protective effect.
Suen, Christopher F D Li Wai; Boyapati, Ray; Simpson, Ian; Dev, Anouk
Sertraline is widely prescribed to treat depression and anxiety disorders. However, hepatitis secondary to its use is a rare entity. We report the case of a 26-year-old woman in her 20th week of pregnancy presented with nausea, vomiting, malaise and dark urine. This occurred 6 months after sertraline 50 mg daily was started for the treatment of depression. Three weeks prior to her presentation, the dose of sertraline was increased to 100 mg daily. The patient's liver biochemical profile demonstrated increased transaminases. The biopsy of the liver showed lobular hepatitis, with a mild prominence of eosinophils, suggestive of a drug-induced or toxin-induced aetiology. Extensive biochemical work-up failed to show any other pathology to account for her hepatitis. Liver function tests normalised after cessation of sertraline, indicating a probable association between sertraline use and acute hepatocellular injury in our patient.
Coca, Steven G
The incidence rate of acute kidney injury (AKI) is highest in elderly patients, who make up an ever-growing segment of the population at large. AKI in these patients is associated with an increased risk of short- and long-term death and chronic kidney disease, including end-stage renal disease. Whether AKI in older individuals carries a larger relative risk for these outcomes compared with younger individuals is unclear at this time. Other domains, such as health-related quality of life, may be mildly impacted on after an episode of AKI. No effective therapies for AKI currently are available for widespread use. However, because the incidence of AKI is highest in the elderly and the phenotype is not discernibly different from AKI in all populations, future randomized controlled trials of interventions for AKI should be performed in the elderly population.
Coca, Steven G.
The incidence rate of acute kidney injury (AKI) is highest in elderly patients, who comprise an ever-growing segment of the population at large. AKI in these patients is associated with an increased risk of short-term and long-term death and chronic kidney disease, including end-stage renal disease. Whether AKI in older individuals carries a larger relative risk for these outcomes compared to younger individuals in unclear at this time. Other domains such as health-related quality of life may be mildly impacted after an episode of AKI. No effective therapies for AKI are currently available for wide-spread use. However, since the incidence of AKI is highest in the elderly and the phenotype is not discernibly different from AKI in all populations, future randomized controlled trials of interventions for AKI should be performed in the elderly population. PMID:20346560
Raised intracranial pressure (ICP) is an important complication of severe brain injury, and is associated with a high mortality rate. Barbiturates are believed to reduce intracranial pressure by suppressing cerebral metabolism, thus reducing cerebral metabolic demands and cerebral blood volume. However, barbiturates also reduce blood pressure and therefore may adversely effect cerebral perfusion pressure. To assess the effects of barbiturates in reducing raised intracranial pressure, mortality and morbidity in people with acute traumatic brain injury. To quantify any side effects resulting from the use of barbiturates. The review draws largely on the search strategy developed for the Cochrane Injuries Group as a whole. However, in addition the Cochrane Library was searched in December 1996 using the text terms "barbiturate*," "pentobarb*," "phenobarb*," "head," and "brain." An updated search was done in April 1999. Randomised or quasi randomised trials of any one or more of the barbiturate class of drugs (amobarbital, barbital, hexobarbital, mephobarbital, methohexital, murexide, pentobarbital, phenobarbital, secobarbital, thiobarbiturate) where study participants had a clinically diagnosed acute traumatic brain injury of any severity. The reviewer extracted the data and assessed the quality of allocation concealment in the trials. The pooled relative risk for death (barbiturate vs no barbiturate) was 1.09 (95%CI 0.81 to 1.47). The pooled effect of barbiturates on adverse neurological outcome, measured using the Glasgow Outcome Scale (death, persistent vegetative state or severe disability) was 1.15 (95% 0.81 to 1.64). Two studies examined the effect of barbiturate therapy on intracranial pressure. In the study by Eisenberger et al, a smaller proportion of patients in the barbiturate group had uncontrolled ICP (68% vs 83%). The relative risk for uncontrolled ICP was 0.81 (95%CI 0.62 to 1.06). Similarly, in the study by Ward et al, mean ICP was lower in the
Mahmood, Ismail; El-Menyar, Ayman; Dabdoob, Wafer; Abdulrahman, Yassir; Siddiqui, Tarriq; Atique, Sajid; Arumugam, Suresh Kumar; Latifi, Rifat; Al-Thani, Hassan
Background: Serum troponin T (TnT) is a common marker of myocardial injury. However, its implication in the absence of clinical evidence of cardiac reason is not well established. Aims: The aim of this study was to identify the implications of positive TnT in traumatic chest injury (TCI) patients regardless of the cardiac involvement. Materials and Methods: We conducted a retrospective analysis of all TCI patients admitted to level 1 trauma center between 2008 and 2011. Patients who underwent TnT testing were divided into two groups: Group 1 (positive TnT) and Group 2 (negative TnT). The two groups were analyzed and compared, and multivariate regression analyses were performed to identify predictors of TnT positivity and mortality. Results: Out of 993 blunt TCI patients, 19.3% had positive TnT (Group 1). On comparison to Group 2, patients in Group 1 were 5 years younger and more likely to have head, cardiac, hepatic, splenic, and pelvic injuries, in addition to lung contusion. Positive TnT was associated with higher Injury Severity Score (ISS) (P = 0.001), higher chest Abbreviated Injury Score (AIS) (P = 0.001), and longer hospital stay (P = 0.03). In addition, Group 1 patients were more likely to undergo chest tube insertion, exploratory laparotomy, mechanical ventilation, and tracheostomy. Twenty patients had cardiac involvement, and of them 14 had positive TnT. Among 973 patients who showed no evidence of cardiac involvement, 178 had positive TnT (18.3%). There were 104 deaths (60% in Group 1). On multivariate regression analysis, the predictors of hospital mortality were positive TnT, head injury, and high ISS, whereas, the predictors of TnT positivity were cardiac, hepatic, and pelvic injuries; higher ISS; and age. Conclusions: Positive TnT in blunt TCI patients is a common challenge, particularly in polytrauma cases. Patients with positive TnT tend to have the worst outcome even in the absence of clinical evidence of acute cardiac involvement. Positive TnT is
Chen, Yu-Wei; Sim, Ming-Ming; Smith, Eric E
Diagnostic and interventional percutaneous coronary catheterization is associated with stroke. Many of such strokes are asymptomatic, but some are devastating. Once the diagnosis of acute cerebral infarction is confirmed, thrombolytic therapy should be administrated within the time window of 3 hours. We report a 61-year-old woman who suffered from an acute cerebral infarction during diagnostic cardiac catheterization for unstable angina, which manifested as sudden onset of global aphasia, right hemiplegia and gaze preponderance to the left side. Computed tomography of the head performed immediately after recognition of the symptoms showed a hyperdense middle cerebral artery (MCA) sign. Following prompt recognition and diagnosis, intravenous thrombolytic therapy was administered 2 hours after symptom onset. The patient had a favorable outcome. Initially, National Institutes of Health Stroke Scale score was 21, and 24 hours later it improved to 9. The hyperdense MCA lesion had resolved on the 24-hour follow-up scan. This case illustrates the clinical benefit of thrombolytic therapy in the setting of acute stroke associated with cardiac catheterization.
He, Liyu; Livingston, Man J; Dong, Zheng
Acute kidney injury (AKI) is a major kidney disease associated with a poor clinical outcome both in the short and long term. Autophagy is a cellular stress response that plays important roles in the pathogenesis of various diseases. Autophagy is induced in proximal tubules during AKI. A renoprotective role of autophagy in AKI has been demonstrated by pharmacological and genetic inhibition studies. The role of autophagy in kidney recovery and repair from AKI, however, remains largely unknown. A dynamic change in autophagy during the recovery phase of AKI seems to be important for tubular proliferation and repair. In renal fibrosis, autophagy may either promote this via the induction of tubular atrophy and decomposition, or prevent it via effects on the intracellular degradation of excessive collagen. Further research is expected to improve the understanding of the regulation of autophagy in kidney injury and repair, elucidate the pathological roles of autophagy in renal fibrosis, and discover therapeutic targets for treating AKI and preventing its progression to chronic kidney disease.
Oddo, Mauro; Crippa, Ilaria Alice; Mehta, Sangeeta; Menon, David; Payen, Jean-Francois; Taccone, Fabio Silvio; Citerio, Giuseppe
Daily interruption of sedative therapy and limitation of deep sedation have been shown in several randomized trials to reduce the duration of mechanical ventilation and hospital length of stay, and to improve the outcome of critically ill patients. However, patients with severe acute brain injury (ABI; including subjects with coma after traumatic brain injury, ischaemic/haemorrhagic stroke, cardiac arrest, status epilepticus) were excluded from these studies. Therefore, whether the new paradigm of minimal sedation can be translated to the neuro-ICU (NICU) is unclear. In patients with ABI, sedation has 'general' indications (control of anxiety, pain, discomfort, agitation, facilitation of mechanical ventilation) and 'neuro-specific' indications (reduction of cerebral metabolic demand, improved brain tolerance to ischaemia). Sedation also is an essential therapeutic component of intracranial pressure therapy, targeted temperature management and seizure control. Given the lack of large trials which have evaluated clinically relevant endpoints, sedative selection depends on the effect of each agent on cerebral and systemic haemodynamics. Titration and withdrawal of sedation in the NICU setting has to be balanced between the risk that interrupting sedation might exacerbate brain injury (e.g. intracranial pressure elevation) and the potential benefits of enhanced neurological function and reduced complications. In this review, we provide a concise summary of cerebral physiologic effects of sedatives and analgesics, the advantages/disadvantages of each agent, the comparative effects of standard sedatives (propofol and midazolam) and the emerging role of alternative drugs (ketamine). We suggest a pragmatic approach for the use of sedation-analgesia in the NICU, focusing on some practical aspects, including optimal titration and management of sedation withdrawal according to ABI severity.
Soltaninejad, Kambiz; Beyranvand, Mohammad-Reza; Momenzadeh, Seyed-Akbar; Shadnia, Shahin
Aluminium phosphide (AlP) poisoning has a high mortality due to cardiovascular involvement. In this study, we evaluated the frequency of cardiac manifestations and electrocardiographic (ECG) findings in 20 patients with acute AlP poisoning, who were admitted to the intensive care unit (ICU) in Tehran, Iran, over a period of 6 months (between October 2008 and April 2009). The sex, age, cause and manner of ingestion, number of ingested AlP tablets, cardiac and ECG manifestations, creatine phosphokinase (CPK), CPK-myocardial band (CPK-mb) and troponin-T (TnT) were extracted from the patients' files. All data were analysed with Statistical Package for the Social Sciences (SPSS) software. The majority (60%) of patients were male. The mean age was 27 ± 8.7 years. The mortality rate was 40%. In all of the patients, the cause of poisoning was intentional suicide and ingestion was the route of exposure. The mean number of ingested AlP tablets per patient was 2.2 ± 1.1. The average time interval between admission and cardiovascular manifestations or ECG findings was 168.8 ± 116.2 min. The range of systolic (SBP) and diastolic blood pressure was 60-130 mmHg and 40-70 mmHg, respectively. Dysrhythmia was observed in nine (45%) cases. Elevation of the ST segment was seen in nine cases (45%). Seven patients (35%) had prolonged QTc intervals. Bundle branch block (BBB) was observed in four (20%) patients. In nine (45%) patients, the serum cardiac TnT qualitative assay was positive. There were no significant differences between normal and abnormal ECG groups according to sex, age, number and manner of ingested AlP tablets and SBP. There was a significant correlation between cardiac manifestations and ECG findings and TnT-positive results with mortality in acute AlP poisoning.
Berbel, Marina Nogueira; Pinto, Milene Peron Rodrigues; Ponce, Daniela; Balbi, André Luís
Nutritional assessment is an indispensable tool for the evaluation and clinical monitoring of patients with acute kidney injury (AKI). Acute loss of renal function interferes with the metabolism of all macronutrients, responsible for proinflammatory, pro-oxidative and hypercatabolic situations. The major nutritional disorders in AKI patients are hypercatabolism, hyperglycemia, and hypertriglyceridemia. Those added to the contributions of the underlying disease, complications, and the need for renal replacement therapy can interfere in the nutritional depletion of those patients. Malnutrition in AKI patients is associated with increased incidence of complications, longer hospitalization, and higher hospital mortality. However, there are few studies evaluating the nutritional status of AKI patients. Anthropometric parameters, such as body mass index, arm circumference, and thickness of skin folds, are difficult to interpret due to changes in hydration status in those patients. Biochemical parameters commonly used in clinical practice are also influenced by non-nutritional factors like loss of liver function and inflammatory status. Although there are no prospective data about the behavior of nutritional markers, some authors demonstrated associations of some parameters with clinical outcomes. The use of markers like albumin, cholesterol, prealbumin, IGF-1, subjective global assessment, and calculation of the nitrogen balance seem to be useful as screening parameters for worse prognosis and higher mortality in AKI patients. In patients with AKI on renal replacement therapy, a caloric intake of 25 to 30 kcal/kg and a minimum amount of 1.5 g/kg/day of protein is recommended to minimize protein catabolism and prevent metabolic complications.
Groeneveld, A B Johan; Polderman, Kees H
Acute lung injury or acute respiratory distress syndrome (ALI/ARDS) in the course of sepsis is thought to result from increased pulmonary capillary permeability and resultant edema. However, when the edema is assessed at the bedside by measuring the extravascular thermal volume by transpulmonary dilution, some ALI/ARDS patients with sepsis may have normal extravascular lung water (EVLW). Conversely, a raised EVLW may be present even when criteria for ALI/ARDS are not met, according to GS Martin and colleagues in this issue of Critical Care. This commentary puts the findings into a broader perspective and focuses on the difficulty, at the bedside, in recognizing and separating various types of pulmonary edema. Some of these forms of edema, classically differentiated on the basis of increased permeability and cardiogenic/hydrostatic factors, may overlap, whereas the criteria for ALI/ARDS may be loose, poorly reproducible, relatively insensitive and nonspecific, and highly therapy-dependent. Overhydration is particularly difficult to recognize. Additional diagnostics may be required to improve the delineation of pulmonary edema so as to redirect or redefine treatment and improve patient morbidity and, perhaps, mortality. Monitoring EVLW by single transpulmonary thermal dilution, for instance, might have a future role in this process.
Schweisfurth, H; Sopivnik, I; Moog, R
Transfusion-related acute lung injury (TRALI) is primarily caused by transfusion of fresh frozen plasma or platelet concentrates and occurs by definition within 6 hours after transfusion with acute shortness of breath, hypoxemia and radiographically detectable bilateral infiltrates of the lung. Mostly leucocyte antibodies in the plasma of the blood donor (immunogenic TRALI) are responsible. Apart from antibodies, other substances such as biologically active lipids, mainly arising from the storage of platelet and red blood cell concentrates, can activate neutrophilic granulocytes and trigger a non-immunogenic TRALI. Pathophysiologically, granulocytes in the capillaries of the lung vessels release oxygen radicals and enzymes which damage the endothelial cells and cause pulmonary edema. Therapeutically, nasal oxygen administration may be sufficient. In severe cases, mechanical ventilation, invasive hemodynamic monitoring and fluid intake are required. Diuretics should be avoided. The administration of glucocorticoids is controversial. Antibody-related TRALI reactions occurred mainly after transfusion of fresh frozen plasma, which had been obtained from womenimmunized during pregnancy against leukocyte antigens. Therefore, in Germany, since 2009 only plasma from female donors without a history of prior or current pregnancy or negative testing for antibodies against HLA I, II or HNA has been used with the result that since then no TRALI-related death has been registered.
Philips, Barbara; MacPhee, Iain
Statins were introduced as lipid-lowering agents with a specific action to decrease plasma cholesterol concentrations and they have led to significant reductions in cardiovascular morbidity and mortality. Since their introduction, they have been found to have highly pleiotropic effects and potential use in many medical conditions well beyond cardiovascular disease alone. With their widespread and increasing use, adverse effects have also become apparent and it is suggested from the interrogation of observational data from large datasets that an early complication of statin use may be acute kidney injury (AKI). This review explores the evidence relating to statins and the risks of AKI. The pathophysiology of AKI is considered and the statins are compared and contrasted. Statins have also been attributed with reno-protective effects and the literature relating to these circumstances are reviewed. The question of whether statins cause AKI remains unresolved. Evidence suggests that statins may both protect or harm kidneys acutely and that risk varies with the condition and the dose and type of statin used. However, any current adverse data should not deter prescription of statins in patients where there is clear evidence for either primary or secondary prevention of cardiovascular events.
Li, Philip Kam Tao; Burdmann, Emmanuel A; Mehta, Ravindra L
Acute kidney injury (AKI) is increasingly prevalent in developing and developed countries and is associated with severe morbidity and mortality. Most etiologies of AKI can be prevented by interventions at the individual, community, regional and in-hospital levels. Effective measures must include community-wide efforts to increase an awareness of the devastating effects of AKI and provide guidance on preventive strategies, as well as early recognition and management. Efforts should be focused on minimizing causes of AKI, increasing awareness of the importance of serial measurements of serum creatinine in high-risk patients, and documenting urine volume in acutely ill people to achieve early diagnosis; there is as yet no definitive role for alternative biomarkers. Protocols need to be developed to systematically manage prerenal conditions and specific infections. More accurate data about the true incidence and clinical impact of AKI will help to raise the importance of the disease in the community, and increase awareness of AKI by governments, the public, general and family physicians and other healthcare professionals to help prevent the disease. Prevention is the key to avoid the heavy burden of mortality and morbidity associated with AKI.
Mathew, Ashish Jacob; George, Jacob
Acute kidney injury (AKI) is one of the most challenging problems faced by clinicians in the tropics owing to its fast-changing burden. AKI in the tropics is strikingly different from that in the developed world in terms of etiology and presentation. In addition, there is a stark contrast between well-developed and poor areas in the tropics. The true epidemiological picture of AKI in the tropics is not well understood due to the late presentation of patients to tertiary centers. Infections remain the major culprit in most cases of AKI, with high mortality rates in the tropics. Human immunodeficiency virus–related AKI, related to nephrotoxicity due to antiretroviral therapy, is on the rise. Acute tubular necrosis and thrombotic microangiopathy are the most common mechanisms of AKI. A notable problem in the tropics is the scarcity of resources in health centers to support patients who require critical care due to AKI. This article reviews the unique and contrasting nature of AKI in the tropics and describes its management in each situation. PMID:21911980
Mathew, Ashish Jacob; George, Jacob
Acute kidney injury (AKI) is one of the most challenging problems faced by clinicians in the tropics owing to its fast-changing burden. AKI in the tropics is strikingly different from that in the developed world in terms of etiology and presentation. In addition, there is a stark contrast between well-developed and poor areas in the tropics. The true epidemiological picture of AKI in the tropics is not well understood due to the late presentation of patients to tertiary centers. Infections remain the major culprit in most cases of AKI, with high mortality rates in the tropics. Human immunodeficiency virus-related AKI, related to nephrotoxicity due to antiretroviral therapy, is on the rise. Acute tubular necrosis and thrombotic microangiopathy are the most common mechanisms of AKI. A notable problem in the tropics is the scarcity of resources in health centers to support patients who require critical care due to AKI. This article reviews the unique and contrasting nature of AKI in the tropics and describes its management in each situation.
Peres, Luis Alberto Batista; Bredt, Luis Cesar; Cipriani, Raphael Flavio Fachini
Currently, partial hepatectomy is the treatment of choice for a wide variety of liver and biliary conditions. Among the possible complications of partial hepatectomy, acute kidney injury (AKI) should be considered as an important cause of increased morbidity and postoperative mortality. Difficulties in the data analysis related to postoperative AKI after liver resections are mainly due to the multiplicity of factors to be considered in the surgical patients, moreover, there is no consensus of the exact definition of AKI after liver resection in the literature, which hampers comparison and analysis of the scarce data published on the subject. Despite this multiplicity of risk factors for postoperative AKI after partial hepatectomy, there are main factors that clearly contribute to its occurrence. First factor relates to large blood losses with renal hypoperfusion during the operation, second factor relates to the occurrence of post-hepatectomy liver failure with consequent distributive circulatory changes and hepatorenal syndrome. Eventually, patients can have more than one factor contributing to post-operative AKI, and frequently these combinations of acute insults can be aggravated by sepsis or exposure to nephrotoxic drugs. PMID:27478539
Dhanapriya, Jeyachandran; Dineshkumar, Thanigachalam; Sakthirajan, Ramanathan; Shankar, Palaniselvam; Gopalakrishnan, Natarajan; Balasubramaniyan, Thoppalan
Background Wasp stings are a common form of envenomation in tropical countries, especially in farmers. The aim of this study was to document the clinical presentation, treatment and outcomes of patients with acute kidney injury (AKI) due to multiple wasp stings in a tertiary care hospital. Methods We conducted a retrospective observational study of patients with multiple wasp stings and AKI at the Department of Nephrology between July 2011 and August 2015. The clinical features, laboratory data, treatment details and outcomes were noted. Results A total of 11 patients were included. All were from rural areas. All of them were males with age ranging from 21 to 70 years, mean age 45 ± 23 years. Six had oliguria and two had hypotension. All 11 patients had evidence of rhabdomyolysis and three also had hemolysis. Ten patients required hemodialysis with a mean number of hemodialysis sessions of 8.7 ± 2.8. Renal biopsy carried out on four patients, showed acute interstitial nephritis (AIN) in one patient, acute tubular necrosis (ATN) in two patients, and one patient had both AIN and ATN. The two patients with AIN were given steroids, while all other patients were managed with supportive measures. One patient died within 48 h of presentation due to shock. At a mean follow-up of 24 months, one had progressed to chronic kidney disease and the remaining nine had normal renal function. Conclusions Wasp sting is an occupational hazard. AKI was most commonly due to rhabdomyolysis. Early renal biopsy is indicated in those patients who do not respond to supportive measures. Timely dialysis and steroid in the case of AIN improves renal survival. PMID:26985369
Hahn, Kai; Kanbay, Mehmet; Lanaspa, Miguel A; Johnson, Richard J; Ejaz, A Ahsan
Acute kidney injury causes great morbidity and mortality in both the community and hospital settings. Understanding the etiological factors and the pathophysiological principles resulting in acute kidney injury is essential in prompting appropriate therapies. Recently hyperuricemia has been recognized as a potentially modifiable risk factor for acute kidney injury, including that associated with cardiovascular surgery, radiocontrast administration, rhabdomyolysis, and associated with heat stress. This review discussed the evidence that repeated episodes of acute kidney injury from heat stress and dehydration may also underlie the pathogenesis of the chronic kidney disease epidemic that is occurring in Central America (Mesoamerican nephropathy). Potential mechanisms for how uric acid might contribute to acute kidney injury are also discussed, including systemic effects on renal microvasculature and hemodynamics, and local crystalline and noncrystalline effects on the renal tubules. Pilot clinical trials also show potential benefits of lowering uric acid on acute kidney injury associated with a variety of insults. In summary, there is mounting evidence that hyperuricemia may have a significant role in the development of acute kidney injury. Prospective, placebo controlled, randomized trials are needed to determine the potential benefit of uric acid lowering therapy on kidney and cardio-metabolic diseases.
Berthiaume, Yves; Matthay, Michael A
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 beta-adrenergic agonists which has generated considerable interest and is a promising therapy for clinical acute lung injury.
Roberts, Ian; Sydenham, Emma
Raised intracranial pressure (ICP) is an important complication of severe brain injury, and is associated with high mortality. Barbiturates are believed to reduce ICP by suppressing cerebral metabolism, thus reducing cerebral metabolic demands and cerebral blood volume. However, barbiturates also reduce blood pressure and may, therefore, adversely effect cerebral perfusion pressure. To assess the effects of barbiturates in reducing mortality, disability and raised ICP in people with acute traumatic brain injury. To quantify any side effects resulting from the use of barbiturates. The following electronic databases were searched on 26 September 2012: CENTRAL (The Cochrane Library), MEDLINE (Ovid SP), PubMed, EMBASE (Ovid SP), PsycINFO (Ovid SP), PsycEXTRA (Ovid SP), ISI Web of Science: Science Citation Index and Conference Proceedings Citation Index-Science. Searching was not restricted by date, language or publication status. We also searched the reference lists of the included trials and review articles. We contacted researchers for information on ongoing studies. Randomised controlled trials of one or more of the barbiturate class of drugs, where study participants had clinically diagnosed acute traumatic brain injury of any severity. Two review authors screened the search results, extracted data and assessed the risk of bias in the trials. Data from seven trials involving 341 people are included in this review.For barbiturates versus no barbiturate, the pooled risk ratio (RR) of death from three trials was 1.09 (95% confidence interval (CI) 0.81 to 1.47). Death or disability, measured using the Glasgow Outcome Scale was assessed in two trials, the RR with barbiturates was 1.15 (95% CI 0.81 to 1.64). Two trials examined the effect of barbiturate therapy on ICP. In one, a smaller proportion of patients in the barbiturate group had uncontrolled ICP (68% versus 83%); the RR for uncontrolled ICP was 0.81 (95% CI 0.62 to 1.06). In the other, mean ICP was also lower in
Tator, C H; Fehlings, M G
In patients with spinal cord injury, the primary or mechanical trauma seldom causes total transection, even though the functional loss may be complete. In addition, biochemical and pathological changes in the cord may worsen after injury. To explain these phenomena, the concept of the secondary injury has evolved for which numerous pathophysiological mechanisms have been postulated. This paper reviews the concept of secondary injury with special emphasis on vascular mechanisms. Evidence is presented to support the theory of secondary injury and the hypothesis that a key mechanism is posttraumatic ischemia with resultant infarction of the spinal cord. Evidence for the role of vascular mechanisms has been obtained from a variety of models of acute spinal cord injury in several species. Many different angiographic methods have been used for assessing microcirculation of the cord and for measuring spinal cord blood flow after trauma. With these techniques, the major systemic and local vascular effects of acute spinal cord injury have been identified and implicated in the etiology of secondary injury. The systemic effects of acute spinal cord injury include hypotension and reduced cardiac output. The local effects include loss of autoregulation in the injured segment of the spinal cord and a marked reduction of the microcirculation in both gray and white matter, especially in hemorrhagic regions and in adjacent zones. The microcirculatory loss extends for a considerable distance proximal and distal to the site of injury. Many studies have shown a dose-dependent reduction of spinal cord blood flow varying with the severity of injury, and a reduction of spinal cord blood flow which worsens with time after injury. The functional deficits due to acute spinal cord injury have been measured electrophysiologically with techniques such as motor and somatosensory evoked potentials and have been found proportional to the degree of posttraumatic ischemia. The histological effects
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
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
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
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.
Chawla, Lakhmir S; Amdur, Richard L; Faselis, Charles; Li, Ping; Kimmel, Paul L; Palant, Carlos E
Pneumonia is a common cause of hospitalization and can be complicated by the development of acute kidney injury. Acute kidney injury is associated with major adverse kidney events (death, dialysis, and durable loss of renal function [chronic kidney disease]). Because pneumonia and acute kidney injury are in part mediated by inflammation, we hypothesized that when acute kidney injury complicates pneumonia, major adverse kidney events outcomes would be exacerbated. We sought to assess the frequency of major adverse kidney events after a hospitalization for either pneumonia, acute kidney injury, or the combination of both. We conducted a retrospective database analysis of the national Veterans Affairs database for patients with a admission diagnosis of International Classification of Diseases-9 code 584.xx (acute kidney injury) or 486.xx (pneumonia) between October 1, 1999, and December 31, 2005. Three groups of patients were created, based on the diagnosis of the index admission and serum creatinine values: 1) acute kidney injury, 2) pneumonia, and 3) pneumonia with acute kidney injury. Patients with mean baseline estimated glomerular filtration rate less than 45 mL/min/1.73 m were excluded. The primary endpoint was major adverse kidney events defined as the composite of death, chronic dialysis, or a permanent loss of renal function after the primary discharge. The observations of 54,894 subjects were analyzed. Mean age was 68.7 ± 12.3 years. The percentage of female was 2.4, 73.3% were Caucasian, and 19.7% were African-American. Differences across the three diagnostic groups were significant for death, 25% decrease in estimated glomerular filtration rate from baseline, major adverse kidney events following admission, and major adverse kidney events during admission (all p < 0.0001). Death alone and major adverse kidney events after discharge were most common in the pneumonia + acute kidney injury group (51% died and 62% reached major adverse kidney events). In both
Veron Esquivel, Daniel; Aello, Gerardo; Batiz, Fernando; Fernandez Barrera, Alejandro
A 41-year-old Hispanic man was admitted to our hospital with the diagnosis of acute pancreatitis due to hypertriglyceridemia. During his stay, he developed sudden haemodynamic instability and clinical presentation suggestive of cardiac tamponade. A transthoracic echocardiogram confirmed the diagnosis. Echocardiography-guided pericardiocentesis was performed with immediate haemodynamic improvement. The patient's condition underwent favourable evolution. The pancreatitis was resolved and a control transthoracic echocardiography was performed showing no pericardial effusion. The pathophysiology of this rare entity is unknown. Early diagnosis and treatment are crucial. Although pericardiocentesis is the treatment of choice, there have been a few reports of medical treatment with encouraging results. Although the association of acute pancreatitis and tamponade are anecdotal in literature, medics should be aware of this association in order to perform prompt diagnosis.
Zahra, Michael; Samdani, Amer; Piggott, Kurt; Gonzalez-Brito, Manuel; Solano, Juan; De Los Santo, Roosevelt; Buitrago, Juan C; Alam, Farid; He, Dansha; Gaughan, John P; Betz, Randal; Dietrich, Dalton; Kuluz, John
Spinal cord injury (SCI) produces acute hemodynamic alterations through disruption of sympathetic output of the autonomic nervous system and places individuals with SCI at high risk of secondary ischemic insult to the spinal cord as well as to other organs. The purpose of this study was to examine hemodynamics and serum vasopressin concentration in the acute period following complete cervical SCI in piglets. We developed a new model of traumatic complete cervical SCI in piglets and measured acute hemodynamic variables and serum arginine vasopressin (AVP) concentrations at baseline and for 4 h after SCI under fentanyl anesthesia. Complete cervical SCI caused an immediate tachycardia which lasted for approximately 1 h, immediate hypotension which was sustained for the 4-h duration of the study, decreases in both systemic and pulmonary vascular resistance, and a compensatory increase in cardiac output, which resulted initially from an increase in heart rate (HR) but was later sustained after resolution of tachycardia by an increase in cardiac stroke volume. Serum AVP concentration increased significantly after SCI and did not change in the control group. Neurogenic shock did not occur due to the robust increase in cardiac output and cardiac stroke volume. Complete cervical SCI produces hemodynamic alterations consistent with the withdrawal of sympathetic tone. Although mean arterial pressure (MAP) decreased significantly after SCI, the increase in serum vasopressin may have played a role in maintaining blood pressure and preventing circulatory collapse, a complication which is encountered frequently in patients with cervical and upper thoracic SCI.
Simonsen, Michelle L; Alessio, Helaine M; White, Peter; Newsom, David L; Hagerman, Ann E
Regular bouts of physical activity may cause changes in gene expression that accumulate over time and ultimately affect phenotypes, such as body weight, blood lipid profile and tumour development. Furthermore, acute activity may affect gene expression and phenotypes differently depending on whether the individual is regularly inactive or active. One-month-old male Sprague-Dawley rats (n = 72) were equally divided into SED (standard laboratory cage, n = 24), PA (large activity box, n = 24) and EX groups (exercise wheel inside standard cage, n = 24). At 3 months of age, half the animals from each group were killed at rest and the other half following 30 min of physical activity. The RNA was extracted from cardiac tissue, and microarray analysis was performed on 27,000 genes. Select gene results were validated using quantitative PCR. No gene expression differences occurred when comparing all 3-month-old groups at rest. A relatively small percentage of genes (1.9%) were differentially expressed (P < 0.05) following acute swimming activity in all groups, but only 37 unique and identifiable genes reached or exceeded twofold differences in expression. The genes Atf3, Fos, Apold1 and Pxdn were expressed differently among SED, PA and EX following acute activity, with a clear separation of the magnitude in gene expression with SED > PA > EX. Differences in gene expression levels in young physically inactive and active animals following acute activity have different regulatory roles in gene networks that affect health-related phenotypes.
Haji, Altaf Gauhar; Sharma, Shekhar; Vijaykumar, DK; Paul, Jerry
Introduction Transfusion-related acute lung injury is emerging as a common cause of transfusion-related adverse events. However, awareness about this entity in the medical fraternity is low and it, consequently, remains a very under-reported and often an under-diagnosed complication of transfusion therapy. Case presentation We report a case of a 46-year old woman who developed acute respiratory and hemodynamic instability following a single unit blood transfusion in the postoperative period. Investigation results were non-specific and a diagnosis of transfusion-related acute lung injury was made after excluding other possible causes of acute lung injury. She responded to symptomatic management with ventilatory and vasopressor support and recovered completely over the next 72 hours. Conclusion The diagnosis of transfusion-related acute lung injury relies on excluding other causes of acute pulmonary edema following transfusion, such as sepsis, volume overload, and cardiogenic pulmonary edema. All plasma containing blood products have been implicated in transfusion-related acute lung injury, with the majority being linked to whole blood, packed red blood cells, platelets, and fresh-frozen plasma. The pathogenesis of transfusion-related acute lung injury may be explained by a "two-hit" hypothesis, involving priming of the inflammatory machinery and then activation of this primed mechanism. Treatment is supportive, with prognosis being substantially better than for most other causes of acute lung injury. PMID:18957111
Alcan, K E; Zabetakis, P M; Marino, N D; Franzone, A J; Michelis, M F; Bruno, M S
Eighteen patients with cardiac tamponade were treated by subxiphoid pericardiotomy performed with the patients under local anesthesia. This group included 9 cases of uremic pericarditis (50%), 5 cases of metastatic cancer (28%), 2 cases of trauma (11%), 1 case of tuberculosis (5.5%), and 1 case of unknown cause. Immediate relief from acute cardiac tamponade was obtained in all 18 cases with only minor and self-limiting postoperative complications, including transient supraventricular arrhythmias (five cases) and fever (five cases). There were no deaths related to either the operative procedure or reaccumulation of the pericardial effusion. The drainage period averaged 9.6 days (range, three to 28 days). Pericardial biopsy was performed in 15 of 18 cases. We conclude that subxiphoid pericardiotomy is a safe and effective method for the management of pericardial effusion of diverse causes. The ability to perform this technique safely using local anesthesia and the capacity to obtain a biopsy specimen under direct visualization make this technique superior to both needle pericardiocentesis and pericardiectomy in the acutely ill patient.
Gainor, B J; Piotrowski, G; Puhl, J; Allen, W C; Hagen, R
The throw and its modifications are integral components of many sports. This study correlates case histories of acute injuries in throwing with a biomechanical analysis of the throwing mechanism. Comparisons are made with a similar analysis of the kick analyzed by the same film technique and computer program. Just prior to ball release, the pitching arm extends through an arc of about 73 degress in 40 msec, beginning with the elbow flexed at 80 degrees. This produces an axial load on the humerus and coincides with a pulse of external torque at the shoulder. This acts as stress protection to the humerus which is developing an internal torque of 14,000 inch-lb prior to ball release. The change in angular velocity, or the angular acceleration, during the throw is acquired in a much shorter time than in the kick. Torque is directly proportional to angular acceleration. This necessitates the development of substantially higher torques in the humerus during the throw than about the knee during a kick. The kinetic energy in the arm is 27,000 inch-lb during the throw. This is much higher than the kinetic energy in the kicking leg because the kinetic energy varies proportionally with the square of the angular velocity of the extremity. The angular velocity of the arm is about twice that of the leg. Thus, the pitching arm contains about four times as much kinetic energy as the kicking leg. These severe overloading conditions predispose the upper extremity to injury in the throwing mechanism.
Kang, Kyung-Wook; Shin, Young Ho; Kang, Seungcheol
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.
Likhvantsev, Valery V; Landoni, Giovanni; Grebenchikov, Oleg A; Skripkin, Yuri V; Zabelina, Tatiana S; Zinovkina, Liudmila A; Prikhodko, Anastasia S; Lomivorotov, Vladimir V; Zinovkin, Roman A
To measure the release of plasma nuclear deoxyribonucleic acid (DNA) and to assess the relationship between nuclear DNA level and acute kidney injury occurrence in patients undergoing cardiac surgery. Cardiovascular anesthesiology and intensive care unit of a large tertiary-care university hospital. Prospective observational study. Fifty adult patients undergoing cardiac surgery. Nuclear DNA concentration was measured in the plasma. The relationship between the level of nuclear DNA and the incidence of acute kidney injury after coronary artery bypass grafting was investigated. Cardiac surgery leads to significant increase in plasma nuclear DNA with peak levels 12 hours after surgery (median [interquartile range] 7.0 [9.6-22.5] µg/mL). No difference was observed between off-pump and on-pump surgical techniques. Nuclear DNA was the only predictor of acute kidney injury between baseline and early postoperative risk factors. The authors found an increase of nuclear DNA in the plasma of patients who had undergone coronary artery bypass grafting, with a peak after 12 hours and an association of nuclear DNA with postoperative acute kidney injury. Copyright © 2017 Elsevier Inc. All rights reserved.
Verrier, R.L.; Mills, A.K.; Skornik, W.A. )
The objective of this project was to determine the effects of acute carbon monoxide exposure on cardiac electrical stability. To obtain a comprehensive assessment, diverse biological models were employed. These involved cardiac electrical testing in the normal and ischemic heart in anesthetized and conscious dogs. The experimental plan was designed both to examine the direct effects of carbon monoxide exposure on the myocardium and to evaluate possible indirect influences through alterations in platelet aggregability or changes in central nervous system activity in the conscious animal. Our results indicate that exposure to relatively high levels of carbon monoxide, leading to carboxyhemoglobin concentrations of up to 20 percent, is without significant effect on ventricular electrical stability. This appears to be the case in the acutely ischemic heart as well as in the normal heart. It is important to note that the total exposure period was in the range of 90 to 124 minutes. The possibility that longer periods of exposure or exacerbation from nicotine in cigarette smoke could have a deleterious effect cannot be excluded. We also examined whether or not alterations in platelet aggregability due to carbon monoxide exposure could be a predisposing factor for cardiac arrhythmias. A model involving partial coronary artery stenosis was used to simulate the conditions under which platelet plugs could lead to myocardial ischemia and life-threatening arrhythmias. We found no changes either in the cycle frequency of coronary blood flow oscillations or in platelet aggregability during carbon monoxide exposure. Thus, carbon monoxide exposure does not appear to alter platelet aggregability or its effect on coronary blood flow during stenosis. In the final series of experiments, we examined the effects of carbon monoxide exposure in the conscious state.
Bruells, C S; Dembinski, R
Treatment of patients suffering from acute lung injury is a challenge for the treating physician. In recent years ventilation of patients with acute hypoxic lung injury has changed fundamentally. Besides the use of low tidal volumes, the most beneficial setting of positive end-expiratory pressure (PEEP) has been in the focus of researchers. The findings allow adaption of treatment to milder forms of acute lung injury and severe forms. Additionally computed tomography techniques to assess the pulmonary situation and recruitment potential as well as bed-side techniques to adjust PEEP on the ward have been modified and improved. This review gives an outline of recent developments in PEEP adjustment for patients suffering from acute hypoxic and hypercapnic lung injury and explains the fundamental pathophysiology necessary as a basis for correct treatment.
Regunath, Hariharan; Ariyamuthu, Venkatesh Kumar; Dalal, Pranavkumar; Misra, Madhukar
Traditional bath salts contain a combination of inorganic salts like Epsom salts, table salt, baking soda, sodium metaphosphate, and borax that have cleansing properties. Since 2010, there have been rising concerns about a new type of substance abuse in the name of "bath salts." They are beta-ketone amphetamine analogs and are derivates of cathinone, a naturally occurring amphetamine analog found in the "khat" plant (Catha edulis). Effects reported with intake included increased energy, empathy, openness, and increased libido. Serious adverse effects reported with intoxication included cardiac, psychiatric, and neurological signs and symptoms. Not much is known about the toxicology and metabolism of these compounds. They inhibit monoamine reuptake (dopamine, nor epinephrine, etc.) and act as central nervous system stimulants with high additive and abuse potential because of their clinical and biochemical similarities to effects from use of cocaine, amphetamine, and 3,4-methylenedioxy-N-methylamphetamine. Deaths associated with use of these compounds have also been reported. We report a case of acute kidney injury associated with the use of "bath salt" pills that improved with hemodialysis.
Angeli, Paolo; Tonon, Marta; Pilutti, Chiara; Morando, Filippo; Piano, Salvatore
Acute kidney injury (AKI) is a common and life-threatening complication in patients with cirrhosis. Recently, new criteria for the diagnosis of AKI have been proposed in patients with cirrhosis by the International Club of Ascites. Almost all types of bacterial infections can induce AKI in patients with cirrhosis representing its most common precipitating event. The bacterial infection-induced AKI usually meets the diagnostic criteria of hepatorenal syndrome (HRS). Well in keeping with the "splanchnic arterial vasodilation hypothesis", it has been stated that HRS develops as a consequence of a severe reduction of effective circulating volume related to splanchnic arterial vasodilation and to an inadequate cardiac output. Nevertheless, the role of bacterial infections in precipitating organ failures, including renal failure, is enhanced when their course is characterized by the development of a systemic inflammatory response syndrome (SIRS), thus, when sepsis occurs. Sepsis has been shown to be capable to induce "per se" AKI in animals as well as in patients conditioning also the features of renal damage. This observation suggests that when precipitated by sepsis, the pathogenesis and the clinical course of AKI also in patients with cirrhosis may differentiate to a certain extent from AKI with another or no precipitating factor. The purpose of this review is to describe the features of AKI precipitated by bacterial infections and to highlight whether infection and/or the development of SIRS may influence its clinical course, and, in particular, the response to treatment.
Basile, David P
Acute kidney injury following folate administration is characterized by a vascular remodeling that is initially proliferative but subsequently results in vascular endothelial loss. Interventions directed toward promoting endothelial growth may preserve vascular structure and therefore renal function. However, angiopoietin-1 therapy in the setting of folate-induced acute kidney injury resulted in an expanded fibrotic response despite apparent preservation of the vasculature, indicating that renal repair responses are complex and vascular-directed therapies should be approached with caution.
Symons, Jordan M; Picca, Stefano
Pediatric nephrologists and critical care physicians are faced with a heterogeneous patient population with varied epidemiology caring for children with acute kidney injury or other diseases that may require renal replacement therapy provision. We have composed 4 detailed case scenarios to highlight the challenges and interdisciplinary approach required for optimal care provision to children, and that serve to direct the different articles contained in this special issue of Seminars of Nephrology devoted to acute kidney injury in children.
Farhan, Serdar; Vogel, Birgit; Tentzeris, Ioannis; Jarai, Rudolf; Freynhofer, Matthias Karl; Smetana, Peter; Egger, Florian; Kautzky-Willer, Alexandra; Huber, Kurt
The aim of the study was to investigate predictors of contrast induced acute kidney injury, in-hospital and long-term mortality in patients with acute coronary syndrome treated by percutaneous coronary intervention. We investigated 536 consecutive patients with acute coronary syndrome who underwent percutaneous coronary intervention. Contrast induced acute kidney injury was classified according to risk, injury, failure, loss of kidney function and end-stage kidney disease/acute kidney injury network (RIFLE/AKIN) criteria into those with normal kidney function, risk, RIFLE stage I and those with stage ⩾ II. We investigated in-hospital, all-cause mortality during index hospitalization and long-term all-cause mortality during the follow-up period of 94 months (interquartile 81.6-108.9 months) in adjustment with parameters of the Global Risk of Acute Coronary Events score. Patients with contrast induced acute kidney injury had worse baseline clinical characteristics and displayed more co-morbidities than patients with normal kidney function. In multivariate logistic regression analysis intra-aortic balloon pump use, congestive heart failure, age >75 years and admission serum creatinine >1.5mg/dl were independent predictors of contrast induced acute kidney injury development. contrast induced acute kidney injury RIFLE stage ⩾ II was an independent predictor of in-hospital mortality (odds ratio 33.16, confidence interval 1.426-770.79, p=0.029) and long-term mortality (hazard ratio 4.713, confidence interval 1.53-14.51, p=0.007) even after adjustment for confounders (variables of Global Risk of Acute Coronary Events score). Contrast induced acute kidney injury is a common complication of acute coronary syndrome patients treated by percutaneous coronary intervention. Advanced deterioration in renal function after percutaneous coronary intervention is an independent predictor for in-hospital and long-term mortality. © The European Society of Cardiology 2015.
Pahwa, Naresh; Bharani, Rajesh; Kumar, Ravindra
To determine the risk factors, course of hospital stay and mortality rate among women with post-partum acute kidney injury (AKI), we studied (of 752 patients with AKI admitted to a tertiary care center during the study period between November 2009 and August 2012) 27 (3.59%) women with post-partum AKI. The data regarding age, parity, cause of renal failure, course of hospital stay and requirement of dialysis were recorded. Sepsis was the major cause (70.3%) of post-partum AKI. Other causes included disseminated intravascular coagulation (55.5%), pre-eclampsia/eclampsia (40.7%), ante- and post-partum hemorrhage (40.7% and 22.2%) and hemolytic anemia and elevated liver enzymes and low platelet count syndrome (29.6%); most patients had more than one cause of AKI. We found a very high prevalence (18.5%) of cortical necrosis in our study patients. A significant correlation was also found between the creatinine level on admission and the period of onset of disease after delivery. In conclusion, several factors are involved in causing post-partum AKI in our population, and sepsis was the most common of them.
Costalonga, Elerson Carlos; Costa e Silva, Verônica Torres; Caires, Renato; Hung, James; Yu, Luis; Burdmann, Emmanuel A
Acute kidney injury (AKI) is associated with extended hospital stays, high risks of in-hospital and long-term mortality, and increased risk of incident and progressive chronic kidney disease. Patients with urological diseases are a high-risk group for AKI owing to the coexistence of obstructive uropathy, older age, and preexistent chronic kidney disease. Nonetheless, precise data on the incidence and outcomes of postoperative AKI in urological procedures are lacking. Benign prostatic hyperplasia and prostate cancer are common diagnoses in older men and are frequently treated with surgical procedures. Whereas severe AKI after prostate surgery in general appears to be unusual, AKI associated with transurethral resection of the prostate (TURP) syndrome and with rhabdomyolysis (RM) after radical prostatectomy have been frequently described. The purpose of this review is to discuss the current knowledge regarding the epidemiology, risk factors, outcomes, prevention, and treatment of AKI associated with prostatic surgery. The mechanisms of TURP syndrome and RM following prostatic surgeries will be emphasized. PMID:25374813
Müller, G. A.
Diabetes mellitus (DM) significantly increases the overall morbidity and mortality, particularly by elevating the cardiovascular risk. The kidneys are severely affected as well, partly as a result of intrarenal athero- and arteriosclerosis but also due to noninflammatory glomerular damage (diabetic nephropathy). DM is the most frequent cause of end-stage renal disease in our society. Acute kidney injury (AKI) remains a clinical and prognostic problem of fundamental importance since incidences have been increased in recent years while mortality has not substantially been improved. As a matter of fact, not many studies particularly addressed the topic “AKI in diabetes mellitus.” Aim of this article is to summarize AKI epidemiology and outcomes in DM and current recommendations on blood glucose control in the intensive care unit with regard to the risk for acquiring AKI, and finally several aspects related to postischemic microvasculopathy in AKI of diabetic patients shall be discussed. We intend to deal with this relevant topic, last but not least with regard to increasing incidences and prevalences of both disorders, AKI and DM. PMID:27974972
Prieto-García, Laura; Pericacho, Miguel; Sancho-Martínez, Sandra M; Sánchez, Ángel; Martínez-Salgado, Carlos; López-Novoa, José Miguel; López-Hernández, Francisco J
Pre-renal acute kidney injury (AKI) results from glomerular haemodynamic alterations leading to reduced glomerular filtration rate (GFR) with no parenchymal compromise. Renin-angiotensin system inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor antagonists (ARAs), non-steroidal anti-inflammatory drugs (NSAIDs) and diuretics, are highly prescribed drugs that are frequently administered together. Double and triple associations have been correlated with increased pre-renal AKI incidence, termed "double whammy" and "triple whammy", respectively. This article presents an integrative analysis of the complex interplay among the effects of NSAIDs, ACEIs/ARAs and diuretics, acting alone and together in double and triple therapies. In addition, we explore how these drug combinations alter the equilibrium of regulatory mechanisms controlling blood pressure (renal perfusion pressure) and GFR to increase the odds of inducing AKI through the concomitant reduction of blood pressure and distortion of renal autoregulation. Using this knowledge, we propose a more general model of pre-renal AKI based on a multi whammy model, whereby several factors are necessary to effectively reduce net filtration. The triple whammy was the only model associated with pre-renal AKI accompanied by a course of other risk factors, among numerous potential combinations of clinical circumstances causing hypoperfusion in which renal autoregulation is not operative or is deregulated. These factors would uncouple the normal BP-GFR relationship, where lower GFR values are obtained at every BP value. Copyright © 2016 Elsevier Inc. All rights reserved.
Eirin, Alfonso; Lerman, Amir; Lerman, Lilach O.
Hypertension remains an important modifiable risk factor for cardiovascular disease, associated with increased morbidity and mortality. Deciphering the mechanisms involved in the pathogenesis of hypertension is critical, as its prevalence continues increasing worldwide. Mitochondria, the primary cellular energy producers, are numerous in parenchymal cells of the heart, kidney, and brain, major target organs in hypertension. These membrane-bound organelles not only maintain cellular respiration but also modulate several functions of the cell including proliferation, apoptosis, generation of reactive oxygen species, and intracellular calcium homeostasis. Therefore, mitochondrial damage and dysfunction compromise overall cell functioning. In recent years, significant advances increased our understanding of mitochondrial morphology, bioenergetics, and homeostasis, and in turn of their role in several diseases, so that mitochondrial abnormalities and dysfunction have been identified in experimental models of hypertension. In this review, we summarize current knowledge of the contribution of dysfunctional mitochondria to the pathophysiology of hypertension-induced cardiac damage, as well as available evidence of mitochondrial injury-induced damage in other organs. Finally, we discuss the capability of antihypertensive therapy to ameliorate hypertensive mitochondrial injury, and the potential position of mitochondria as therapeutic targets in patients with hypertension. PMID:25385092
Huang, Kuo-Chin; Hsu, Wei-Hsiu; Wang, Ting-Chung
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.
Shao, Xinghua; Tian, Lei; Xu, Weijia; Zhang, Zhen; Wang, Chunlin; Qi, Chaojun; Ni, Zhaohui; Mou, Shan
Urinary Kidney Injury Molecule 1 (KIM-1) is a proximal tubular injury biomarker for early detection of acute kidney injury (AKI), with variable performance characteristics depending on clinical and population settings. Meta-analysis was performed to assess the diagnostic value of urinary KIM-1 in AKI. Relevant studies were searched from MEDLINE, EMBASE, Pubmed, Elsevier Science Direct, Scopus, Web of Science, Google Scholar and Cochrane Library. Meta-analysis methods were used to pool sensitivity and specificity and to construct summary receiver operating characteristic (SROC) curves. A total of 2979 patients from 11 eligible studies were enrolled in the analysis. Five prospective cohorts, two cross-sectional and four case-control studies were identified for meta-analysis. The estimated sensitivity of urinary KIM-1 for the diagnosis of AKI was 74.0% (95% CI, 61.0%-84.0%), and specificity was 86.0% (95% CI, 74.0%-93.0%). The SROC analysis showed an area under the curve of 0.86(0.83-0.89). Subgroup analysis suggested that population settings and detection time were the key factors affecting the efficiency of KIM-1 for AKI diagnosis. Various population settings, different definition of AKI and Serum creatinine level used as the standard might have influence on AKI diagnosis. The relatively small number of studies and heterogeneity between them also affected the evaluation. Urinary KIM-1 may be a promising biomarker for early detection of AKI with considerable predictive value, especially for cardiac surgery patients, and its potential value needs to be validated in large studies and across a broader scope of clinical settings.
Galeiras Vázquez, R; Ferreiro Velasco, M E; Mourelo Fariña, M; Montoto Marqués, A; Salvador de la Barrera, S
Traumatic spinal cord injury requires a multidisciplinary approach both for specialized treatment of the acute phase and for dealing with the secondary complications. A suspicion or diagnosis of spinal cord injury is the first step for a correct management. A review is made of the prehospital management and characteristics of the acute phase of spinal cord injury. Respiratory monitoring for early selective intubation, proper identification and treatment of neurogenic shock are essential for the prevention of secondary spinal cord injury. The use of corticosteroids is currently not a standard practice in neuroprotective treatment, and hemodynamic monitoring and early surgical decompression constitute the cornerstones of adequate management. Traumatic spinal cord injury usually occurs as part of multiple trauma, and this can make diagnosis difficult. Neurological examination and correct selection of radiological exams prevent delayed diagnosis of spinal cord injuries, and help to establish the prognosis.
DeGracia, Donald J.; Tri Anggraini, Fika; Taha, Doaa Taha Metwally; Huang, Zhi-Feng
Many clinically relevant forms of acute injury, such as stroke, traumatic brain injury, and myocardial infarction, have resisted treatments to prevent cell death following injury. The clinical failures can be linked to the currently used inductive models based on biological specifics of the injury system. Here we contrast the application of inductive and deductive models of acute cell injury. Using brain ischemia as a case study, we discuss limitations in inductive inferences, including the inability to unambiguously assign cell death causality and the lack of a systematic quantitative framework. These limitations follow from an overemphasis on qualitative molecular pathways specific to the injured system. Our recently developed nonlinear dynamical theory of cell injury provides a generic, systematic approach to cell injury in which attractor states and system parameters are used to quantitatively characterize acute injury systems. The theoretical, empirical, and therapeutic implications of shifting to a deductive framework are discussed. We illustrate how a deductive mathematical framework offers tangible advantages over qualitative inductive models for the development of therapeutics of acutely injured biological systems. PMID:27437490
van den Bekerom, Michel P J; Kerkhoffs, Gino M M J; McCollum, Graham A; Calder, James D F; van Dijk, C Niek
Inversion injuries involve about 25 % of all injuries of the musculoskeletal system and about 50 % of these injuries are sport-related. This article reviews the acute lateral ankle injuries with special emphasis on a rationale for treatment of these injuries in athletes. A narrative review was performed using Pubmed/Medline, Ovid and Embase using key words: ankle ligaments, injury, lateral ligament, ankle sprain and athlete. Articles related to the topic were included and reviewed. It is estimated that one inversion injury of the ankle occurs for every 10,000 people each day. Ankle sprains constitute 7-10 % of all admissions to hospital emergency departments. Inversion injuries involve about 25 % of all injuries of the musculoskeletal system, and about 50 % of these injuries are sport-related. The lateral ankle ligament complex consists of three ligaments: the anterior talofibular ligament, the calcaneofibular ligament and the posterior talofibular ligament. The most common trauma mechanism is supination and adduction (inversion) of the plantar-flexed foot. Delayed physical examination provides a more accurate diagnosis. Ultrasound and MRI can be useful in diagnosing associated injury and are routine investigations in professional athletes. Successful treatment of grade II and III acute lateral ankle ligament injuries can be achieved with individualized aggressive, non-operative measures. RICE therapy is the treatment of choice for the first 4-5 days to reduce pain and swelling. Initially, 10-14 days of immobilization in a below the knee cast/brace is beneficial followed by a period in a lace-up brace or functional taping reduces the risk of recurrent injury. Acute repair of the lateral ankle ligaments in grade III injuries in professional athletes may give better results.
Decock, Mathieu; De Wilde, Lieven; Vanden Bossche, Luc; Steyaert, Adelheid; Van Tongel, Alexander
Despite the ever-increasing popularity of bicycle racing, the high perceived risk of acute injuries and the recent media attention, studies of acute injuries in road cyclists are rather scarce. The goal of this study is to evaluate the incidence, aetiology and patterns of acute injuries in non-professional competitive road cyclists during cycling races in Flanders. All acute injuries that occurred during competition in Flanders in 2002 and 2012, collected in the injury registry, were analysed. The incidence, injury rate, diagnosis, circumstances and level of performance were evaluated. A total of 777 documented reports of accidents (1230 injuries) were retrieved for the years 2002 and 2012. There was no significant difference between incidence and injury rate between 2002 and 2012. There was a strong significant difference in the incidence between the different levels of performance in both seasons. Severe injuries were seen in 29.5% in 2002 and in 30.1% in 2012. The most common location of a severe injury was the hand. Collision with another rider was the most common cause of injury. Almost 1 out of 6 non-professional competitive road cyclists had an accident during cycling races in 2002 and 2012 in Flanders and collision with other riders was the most important cause of a crash. The most common lesion was abrasion, but almost one out of three riders had a severe injury. 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/
Warner, M; Baker, S P; Li, G; Smith, G S
Motor vehicle manufacturing, with its varied tasks, challenging work environment, and diverse worker populations, presents many hazards to employees. This study examined routinely collected surveillance data from a major motor vehicle manufacturer to identify injury types, high-risk workers, causes of injury, and factors associated with work loss. Injury and personnel data were used to calculate injury rates. Injury data were from the routinely collected medical and safety surveillance system on occupational injuries. The number of persons working in the plants was estimated using year-end personnel reports. Key word searches supplementing the analyses provided insight into the specific circumstances of injury. The most common injuries were sprains/strains (39% of the total), lacerations (22%), and contusions (15%). Forty-nine percent of the injuries resulted in one or more lost or restricted workdays; 25% resulted in 7 or more lost or restricted workdays. The injuries most likely to result in work loss were amputations, hernias and fractures. Sprains/strains accounted for 65% of all lost workdays. Injury rates ranged from 13.8 per 100 person-years at stamping plants to 28.7 at parts depots. Even within similar types of plants, injury rates varied widely, with a twofold difference among the individual assembly plants in overall injury rates. Injury surveillance systems with descriptive data on injury events shed light on the circumstances under which certain types of injuries occur and can provide the basis for preventive interventions. Sources of variation and potential biases are discussed, providing guidance for those interested in designing and using surveillance systems for occupational injuries.
Atalan, Hakan K; Gucyetmez, Bulent; Aslan, Serdar; Yazar, Serafettin; Polat, Kamil Y
There are many risk factors for postoperative acute kidney injury in liver transplantation. The aim of this study is to investigate the risk factors for postoperative acute kidney injury in living donor liver transplantation recipients. 220 living donor liver transplantation recipients were retrospectively evaluated in the study. According to the Kidney Disease Improving Global Outcomes Guidelines, acute kidney injury in postoperative day 7 was investigated for all patients. The patient's demographic data, preoperative and intraoperative parameters, and outcomes were recorded. Acute kidney injury was found in 27 (12.3%) recipients. In recipients with acute kidney injury, female population, model for end-stage liver disease score, norepinephrine requirement, duration of mean arterial pressure less than 60 mmHg, the usage of gelatin and erythrocyte suspension and blood loss were significantly higher than recipients with nonacute kidney injury (for all p<0.05). In multivariate analyses, the likelihood of acute kidney injury on postoperative day 7 were increased 2.8-fold (1.1-7.0), 2.7-fold (1.02-7.3), 3.4-fold (1.2-9.9) and 5.1-fold (1.7-15.0) by postoperative day 7, serum tacrolimus level ≥10.2 ng dL-1, intraoperative blood loss ≥14.5 mL kg-1, the usage of gelatin >5 mL kg-1 and duration of MAP less than 60 mmHg ≥5.5 minutes respectively (for all p<0.05). In living donor liver transplantation recipients, serum tacrolimus levels, intraoperative blood loss, hypotension period and the usage of gelatin may be risk factors for acute kidney injury in the early postoperative period.
Nadkarni, Girish N; Patel, Achint A; Konstantinidis, Ioannis; Mahajan, Abhimanyu; Agarwal, Shiv Kumar; Kamat, Sunil; Annapureddy, Narender; Benjo, Alexandre; Thakar, Charuhas V
The epidemiology of dialysis requiring acute kidney injury (AKI-D) in acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) admissions is poorly understood with previous studies being from a single center or year. We used the Nationwide Inpatient Sample to evaluate the yearly incidence trends of AKI-D in hospitalizations with AIS and ICH from 2002 to 2011. We also evaluated the trend of impact of AKI-D on in-hospital mortality and adverse discharge using adjusted odds ratios (aOR) after adjusting for demographics and comorbidity indices. We extracted a total of 3,937,928 and 696,754 hospitalizations with AIS and ICH, respectively. AKI-D occurred in 1.5 and 3.5 per 1000 in AIS and ICH admissions, respectively. Incidence of admissions complicated by AKI-D doubled from 0.9/1000 to 1.7/1000 in AIS and from 2.1/1000 to 4.3/1000 in ICH admissions. In AIS admissions, AKI-D was associated with 30% higher odds of mortality (aOR, 1.30; 95% confidence interval, 1.12-1.48; P<0.001) and 18% higher odds of adverse discharge (aOR, 1.18; 95% confidence interval, 1.02-1.37; P<0.001). Similarly, in ICH admissions, AKI-D was associated with twice the odds of mortality (aOR, 1.95; 95% confidence interval, 1.61-2.36; P<0.01) and 74% higher odds of adverse discharge (aOR, 1.74; 95% confidence interval, 1.34-2.24; P<0.01). Attributable risk percent of mortality was high with AKI-D (98%-99%) and did not change significantly over the study period. Incidence of AKI-D complicating hospitalizations with cerebrovascular accident continues to grow and is associated with increased mortality and adverse discharge. This highlights the need for early diagnosis, better risk stratification, and preparedness for need for complex long-term care in this vulnerable population. © 2015 American Heart Association, Inc.
Leskovar, A; Turek, J; Borgens, R B
Using a cell-isolation and -culture procedure specific for macrophages, we report the existence of giant (more than 50 microm diameter), multinucleated macrophages within an acute, 5-day-old adult rat spinal cord injury. The size and multinuclearity of these isolated giant cells was confirmed using transmission electron microscopy. Giant macrophages are markers for long-term infection, disease, and chronic injury in other soft tissues and are unexpected in the acute inflammatory stage of central nervous system injury. To our knowledge, this descriptive report is the first confirming the existence of giant macrophages in any injured nervous tissue, with additional data suggesting some of these cells to be multinucleated.
Chan, P S; Steinberg, D R; Bozentka, D J
A question commonly asked of physicians focuses on the possible deleterious effects of knuckle cracking. Patients are usually concerned that the risk of arthritis is increased by the habit; however, reports addressing the potential long-term consequence are controversial. We present two cases in which acute injuries were suffered while the patients were attempting to crack their knuckles. Both injuries responded well to conservative treatment. Our investigation shows that acute injuries can result from the forceful manipulation needed to achieve the audible pop of cracking knuckles and that patients should be counseled accordingly.
Martín Cleary, Catalina; Moreno, Juan Antonio; Fernández, Beatriz; Ortiz, Alberto; Parra, Emilio G; Gracia, Carolina; Blanco-Colio, Luis M; Barat, Antonio; Egido, Jesús
Macroscopic haematuria of glomerular origin has been associated with acute kidney injury. We report a patient with IgA nephropathy, macroscopic haematuria and acute kidney injury. Systemic anticoagulation may have aggravated haematuria. There was extensive interstitial and intratubular red blood cell extravasation, and interstitial haemosiderin deposits. The abundant presence of macrophages expressing the haemoglobin scavenger receptor CD163 and of cells stained for oxidative stress markers (NADPH-p22 phox and heme-oxigenase-1) in areas of interstitial haemorrhage and red blood cell cast-containing tubules provided evidence for a role for free haemoglobin in tubulointerstitial renal injury in human glomerular disease.
Lavallee, Mark E; Balam, Tucker
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.
McNeely, Jonathan; Parikh, Samir; Valentine, Christopher; Haddad, Nabil; Shidham, Ganesh; Rovin, Brad; Hebert, Lee; Agarwal, Anil
Bath salts are substance of abuse that are becoming more common and are difficult to recognize due to negative toxicology screening. Acute kidney injury due to bath salt use has not previously been described. We present the case of a previously healthy male who developed acute kidney injury and dialysis dependence after bath salt ingestion and insufflation. This was self-reported with negative toxicology screening. Clinical course was marked by severe hyperthermia, hyperkalemia, rhabdomyolysis, disseminated intravascular coagulation, oliguria, and sepsis. We discuss signs and symptoms, differential diagnoses, potential mechanisms of injury, management, and review of the literature related to bath salt toxicity. PMID:24555135
McNeely, Jonathan; Parikh, Samir; Valentine, Christopher; Haddad, Nabil; Shidham, Ganesh; Rovin, Brad; Hebert, Lee; Agarwal, Anil
Bath salts are substance of abuse that are becoming more common and are difficult to recognize due to negative toxicology screening. Acute kidney injury due to bath salt use has not previously been described. We present the case of a previously healthy male who developed acute kidney injury and dialysis dependence after bath salt ingestion and insufflation. This was self-reported with negative toxicology screening. Clinical course was marked by severe hyperthermia, hyperkalemia, rhabdomyolysis, disseminated intravascular coagulation, oliguria, and sepsis. We discuss signs and symptoms, differential diagnoses, potential mechanisms of injury, management, and review of the literature related to bath salt toxicity.
Hadjizacharia, Pantelis; Beale, Elizabeth O; Inaba, Kenji; Chan, Linda S; Demetriades, Demetrios
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 Scale
Ho, Phoebe Wing-Lam; Pang, Wing-Fai; Szeto, Cheuk-Chun
Acute kidney injury (AKI) is a common complication associated with high morbidity and mortality in hospitalized patients. One potential mechanism underlying renal injury is ischaemia/reperfusion injury (IRI), which attributed the organ damage to the inflammatory and oxidative stress responses induced by a period of renal ischaemia and subsequent reperfusion. Therapeutic strategies that aim at minimizing the effect of IRI on the kidneys may prevent AKI and improve clinical outcomes significantly. In this review, we examine the technique of remote ischaemic preconditioning (rIPC), which has been shown by several trials to confer organ protection by applying transient, brief episodes of ischaemia at a distant site before a larger ischaemic insult. We provide an overview of the current clinical evidence regarding the renoprotective effect of rIPC in the key clinical settings of cardiac or vascular surgery, contrast-induced AKI, pre-existing chronic kidney disease (CKD) and renal transplantation, and discuss key areas for future research.
Onan, Burak; Demirhan, Recep; Öz, Kürşad; Onan, Ismihan Selen
Cardiovascular injuries after trauma present with high mortality. The aim of the study was to present our experience in cardiac and great vessel injuries after chest trauma. During the 10-year period, 104 patients with cardiac (n=94) and great vessel (n=10) injuries presented to our hospital. The demographic data, mechanism of injury, location of injury, other associated injuries, timing of surgical intervention, surgical approach, and clinical outcome were reviewed. Eighty-eight (84.6%) males presented after chest trauma. The mean age of the patients was 32.5±8.2 years (range: 12-76). Penetrating injuries (62.5%) were the most common cause of trauma. Computed tomography was performed in most cases and echocardiography was used in some stable cases. Cardiac injuries mostly included the right ventricle (58.5%). Great vessel injuries involved the subclavian vein in 6, innominate vein in 1, vena cava in 1, and descending aorta in 2 patients. Early operations after admission to the emergency were performed in 75.9% of the patients. Thoracotomy was performed in 89.5% of the patients. Operative mortality was significantly high in penetrating injuries (p=0.01). Clinicians should suspect cardiac and great vessel trauma in every patient presenting to the emergency unit after chest trauma. Computed tomography and echocardiography are beneficial in the management of chest trauma. Operative timing depends on hemodynamic status, and a multidisciplinary team approach improves the patient's prognosis.
Tujjar, Omar; Belloni, Ilaria; Hougardy, Jean-Michel; Scolletta, Sabino; Vincent, Jean-Louis; Creteur, Jacques; Taccone, Fabio S
Acute kidney injury (AKI) is common in critically ill patients and may contribute to poor outcome. Few data are available on the incidence and impact of AKI in patients suffering from nontraumatic subarachnoid hemorrhage (SAH). We reviewed all patients admitted to our Department of Intensive Care with SAH over a 3-year period. Exclusion criteria were time from SAH symptoms to intensive care unit (ICU) admission >96 hours and ICU stay <48 hours. AKI was defined as sustained oligoanuria (urine output <0.5 mL/kg/h for 24 h) or an increase in plasma creatinine (≥0.3 mg/dL or a 1.5-fold increase from baseline level within 48 h). Neurological status was assessed at day 28 using the Glasgow Outcome Scale (GOS) (from 1=death to 5=good recovery; favorable outcome=GOS 4 to 5). Of 243 patients admitted for SAH during the study period, 202 met the inclusion/exclusion criteria (median age 56 y, 78 male). Twenty-five patients (12%) developed AKI, a median of 8 (4 to 10) days after admission. Independent predictors of AKI were development of clinical vasospasm, and treatment with vancomycin. AKI was more frequent in ICU nonsurvivors than in survivors (11/50 vs. 14/152, P=0.03), and in patients with an unfavorable neurological outcome than in other patients (17/93 vs. 8/109, P=0.03). Nevertheless, in multivariable regression analysis, AKI was not an independent predictor of outcome. AKI occurred in >10% of patients after SAH. These patients had more severe neurological impairment and needed more aggressive ICU therapy; AKI did not significantly influence outcome.
Matheny, Michael E; Peterson, Josh F; Eden, Svetlana K; Hung, Adriana M; Speroff, Theodore; Abdel-Kader, Khaled; Parr, Sharidan K; Ikizler, T Alp; Siew, Edward D
Patients with hospitalized acute kidney injury (AKI) are at increased risk for accelerated loss of kidney function, morbidity, and mortality. We sought to inform efforts at improving post-AKI outcomes by describing the receipt of renal-specific laboratory test surveillance among a large high-risk cohort. We acquired clinical data from the Electronic health record (EHR) of 5 Veterans Affairs (VA) hospitals to identify patients hospitalized with AKI from January 1st, 2002 to December 31st, 2009, and followed these patients for 1 year or until death, enrollment in palliative care, or improvement in renal function to estimated GFR (eGFR) ≥ 60 L/min/1.73 m(2). Using demographic data, administrative codes, and laboratory test data, we evaluated the receipt and timing of outpatient testing for serum concentrations of creatinine and any as well as quantitative proteinuria recommended for CKD risk stratification. Additionally, we reported the rate of phosphorus and parathyroid hormone (PTH) monitoring recommended for chronic kidney disease (CKD) patients. A total of 10,955 patients admitted with AKI were discharged with an eGFR<60 mL/min/1.73 m2. During outpatient follow-up at 90 and 365 days, respectively, creatinine was measured on 69% and 85% of patients, quantitative proteinuria was measured on 6% and 12% of patients, PTH or phosphorus was measured on 10% and 15% of patients. Measurement of creatinine was common among all patients following AKI. However, patients with AKI were infrequently monitored with assessments of quantitative proteinuria or mineral metabolism disorder, even for patients with baseline kidney disease.
Matheny, Michael E.; Peterson, Josh F.; Eden, Svetlana K.; Hung, Adriana M.; Speroff, Theodore; Abdel-Kader, Khaled; Parr, Sharidan K.; Ikizler, T. Alp; Siew, Edward D.
Background Patients with hospitalized acute kidney injury (AKI) are at increased risk for accelerated loss of kidney function, morbidity, and mortality. We sought to inform efforts at improving post-AKI outcomes by describing the receipt of renal-specific laboratory test surveillance among a large high-risk cohort. Methods We acquired clinical data from the Electronic health record (EHR) of 5 Veterans Affairs (VA) hospitals to identify patients hospitalized with AKI from January 1st, 2002 to December 31st, 2009, and followed these patients for 1 year or until death, enrollment in palliative care, or improvement in renal function to estimated GFR (eGFR) ≥60 L/min/1.73 m2. Using demographic data, administrative codes, and laboratory test data, we evaluated the receipt and timing of outpatient testing for serum concentrations of creatinine and any as well as quantitative proteinuria recommended for CKD risk stratification. Additionally, we reported the rate of phosphorus and parathyroid hormone (PTH) monitoring recommended for chronic kidney disease (CKD) patients. Results A total of 10,955 patients admitted with AKI were discharged with an eGFR<60 mL/min/1.73 m2. During outpatient follow-up at 90 and 365 days, respectively, creatinine was measured on 69% and 85% of patients, quantitative proteinuria was measured on 6% and 12% of patients, PTH or phosphorus was measured on 10% and 15% of patients. Conclusions Measurement of creatinine was common among all patients following AKI. However, patients with AKI were infrequently monitored with assessments of quantitative proteinuria or mineral metabolism disorder, even for patients with baseline kidney disease. PMID:25117447
Simonini, Marco; Lanzani, Chiara; Bignami, Elena; Casamassima, Nunzia; Frati, Elena; Meroni, Roberta; Messaggio, Elisabetta; Alfieri, Ottavio; Hamlyn, John; Body, Simon C.; Collard, C. David; Zangrillo, Alberto; Manunta, Paolo; Body, Simon C.; Daniel Muehlschlegel, J.; Shernan, Stanton K.; Fox, Amanda A.; David Collard, C.
Background Acute kidney injury (AKI) is an important complication of cardiac surgery. Recently, elevated levels of endogenous ouabain (EO), an adrenal stress hormone with haemodynamic and renal effects, have been associated with worse renal outcome after cardiac surgery. Our aim was to develop and evaluate a new risk model of AKI using simple preoperative clinical parameters and to investigate the utility of EO. Methods The primary outcome was AKI according to Acute Kidney Injury Network stage II or III. We selected the Northern New England Cardiovascular Disease Study Group (NNECDSG) as a reference model. We built a new internal predictive risk model considering common clinical variables (CLIN-RISK), compared this model with the NNECDSG model and determined whether the addition of preoperative plasma EO improved prediction of AKI. Results All models were tested on >800 patients admitted for elective cardiac surgery in our hospital. Seventy-nine patients developed AKI (9.9%). Preoperative EO levels were strongly associated with the incidence of AKI and clinical complication (total ICU stay and in-hospital mortality). The NNECDSG model was confirmed as a good predictor of AKI (AUC 0.74, comparable to the NNECDSG reference population). Our CLIN-RISK model had improved predictive power for AKI (AUC 0.79, CI 95% 0.73–0.84). Furthermore, addition of preoperative EO levels to both clinical models improved AUC to 0.79 and to 0.83, respectively (ΔAUC +0.05 and +0.04, respectively, P < 0.01). Conclusion In a population where the predictive power of the NNECDSG model was confirmed, CLIN-RISK was more powerful. Both clinical models were further improved by the addition of preoperative plasma EO levels. These new models provide improved predictability of the relative risk for the development of AKI following cardiac surgery and suggest that EO is a marker for renal vascular injury. PMID:24920842
Ma, Junpeng; Huang, Siqing; Qin, Shu; You, Chao; Zeng, Yunhui
Traumatic brain injury (TBI) is a leading cause of death and disability, and the identification of effective, inexpensive and widely practicable treatments for brain injury is of great public health importance worldwide. Progesterone is a naturally produced hormone that has well-defined pharmacokinetics, is widely available, inexpensive, and has steroidal, neuroactive and neurosteroidal actions in the central nervous system. It is, therefore, a potential candidate for treating TBI patients. However, uncertainty exists regarding the efficacy of this treatment. This is an update of our previous review of the same title, published in 2012. To assess the effects of progesterone on neurologic outcome, mortality and disability in patients with acute TBI. To assess the safety of progesterone in patients with acute TBI. We updated our searches of the following databases: the Cochrane Injuries Group's Specialised Register (30 September 2016), the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 9, 2016), MEDLINE (Ovid; 1950 to 30 September 2016), Embase (Ovid; 1980 to 30 September 2016), Web of Science Core Collection: Conference Proceedings Citation Index-Science (CPCI-S; 1990 to 30 September 2016); and trials registries: Clinicaltrials.gov (30 September 2016) and the World Health Organization (WHO) International Clinical Trials Registry Platform (30 September 2016). We included randomised controlled trials (RCTs) of progesterone versus no progesterone (or placebo) for the treatment of people with acute TBI. Two review authors screened search results independently to identify potentially relevant studies for inclusion. Independently, two review authors selected trials that met the inclusion criteria from the results of the screened searches, with no disagreement. We included five RCTs in the review, with a total of 2392 participants. We assessed one trial to be at low risk of bias; two at unclear risk of bias (in one multicentred trial the possibility of
Machado, Susana; Figueiredo, Nuno; Borges, Andreia; São José Pais, Maria; Freitas, Luís; Moura, Paulo; Campos, Mário
The incidence of acute kidney injury in pregnancy declined significantly over the second half of the 20th century; however, it is still associated with major maternal and perinatal morbidity and mortality. A set of systemic and renal physiological adaptive mechanisms occur during a normal gestation that will constrain several changes in laboratory parameters of renal function, electrolytes, fluid and acid-base balances. The diagnosis of acute kidney injury in pregnancy is based on the serum creatinine increase. The usual formulas for estimating glomerular filtration rate are not validated in this population. During the first trimester of gestation, acute kidney injury develops most often due to hyperemesis gravidarum or septic abortion. In the third trimester, the differential diagnosis is more challenging for the obstetrician and the nephrologist and comprises some pathologies that are reviewed in this article: preeclampsia/HELLP syndrome, acute fatty liver of pregnancy and thrombotic microangiopathies.
Chirumamilla, Vasu; Prabhakaran, Kartik; Patrizio, Petrone; Savino, John A.; Marini, Corrado P.; Zoha, Zobair
Introduction Work site injuries involving high projectile tools such as nail guns can lead to catastrophic injuries. Generally, penetrating cardiac injuries are associated with a high mortality rate. Presentation of case A construction worker was brought to the emergency room having sustained a nail gun injury to the chest. The patient was hypotensive, tachycardic with prominent jugular venous distention, and had a profound lactic acidosis. Bedside ultrasound confirmed the presence of pericardial fluid. Pericardiocentesis was performed twice using a central venous catheter inserted into the pericardial space, resulting in improvement in the patient’s hemodynamics. Thereafter he underwent left anterolateral thoracotomy and repair of a right atrial laceration. He recovered uneventfully. Discussion Penetrating cardiac injuries caused by nail guns, although rare, have been previously described. However, pericardiocentesis, while retaining a role in the management of medical causes of cardiac tamponade, has been reported only sporadically in the setting of trauma. We report a rare case of penetrating nail gun injury to the heart where pericardiocentesis was used as a temporizing measure to stabilize the patient in preparation for definitive but timely operative intervention. Conclusion We propose awareness that percardiocentesis can serve as a temporary life saving measure in the setting of trauma, particularly as a bridge to definitive therapy. To our knowledge, this represents the first reported case of catheter pericardiocentesis used to stabilize a patient until definitive repair of a penetrating cardiac injury caused by a nail gun. PMID:27107304
Vogiatzis, I; Dapcevic, I
Background Coronary artery dissection is a rare complication of blunt thoracic trauma which can become rapidly lethal necessitating prompt diagnosis and treatment. Most reported cases of coronary artery injury, including dissection, involve the left anterior descending coronary artery, given its anatomical location in relation to the impact. Description of case A 72-year-old male, who was involved in a vehicular accident, sustained blunt thoracic trauma which resulted in isolated right coronary artery dissection and acute myocardial infarction. The culprit lesion was found in coronary angiography in the proximal right coronary artery and was successfully repaired with percutaneous coronary intervention and one drug-eluting stent placement. Conclusion Traumatic dissection of coronary arteries must be suspected in blunt thoracic trauma. It can be treated with interventional management and results in a fairly good prognosis. Hippokratia 2015; 19 (3): 278-280. PMID:27418793
Yang, Seo Hee; Song, Yeon Han; Kim, Tae Hoon; Kim, Su Bin; Han, Sang Youb; Kim, Han-Seong
Multiple wasp stings can induce multiple organ dysfunction by toxic reactions. However, acute pancreatitis is a rare manifestation in wasp sting injury. A 74-year-old woman visited the emergency department by anaphylactic shock because of multiple wasp stings. Acute kidney injury, rhabdomyolysis, hepatotoxicity, and coagulopathy were developed next day. Serum amylase and lipase were elevated and an abdominal computed tomography revealed an acute pancreatitis. Urine output was recovered after 16 days of oliguria (below 500 ml/day). Her kidney, liver, and pancreas injury gradually improved after sessions of renal replacement therapy. PMID:28706746
Siegmund, Gunter P; Winkelstein, Beth A; Ivancic, Paul C; Svensson, Mats Y; Vasavada, Anita
Whiplash injury is the most common motor vehicle injury, yet it is also one of the most poorly understood. Here we examine the evidence supporting an organic basis for acute and chronic whiplash injuries and review the anatomical sites within the neck that are potentially injured during these collisions. For each proposed anatomical site--facet joints, spinal ligaments, intervertebral discs, vertebral arteries, dorsal root ganglia, and neck muscles--we present the clinical evidence supporting that injury site, its relevant anatomy, the mechanism of and tolerance to injury, and the future research needed to determine whether that site is responsible for some whiplash injuries. This article serves as a snapshot of the current state of whiplash biomechanics research and provides a roadmap for future research to better understand and ultimately prevent whiplash injuries.
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).
Dixon, B; Smith, R; Santamaria, J D; Orford, N R; Wakefield, B J; Ives, K; McKenzie, R; Zhang, B; Yap, C H
Cardiac surgery with cardiopulmonary bypass triggers an acute inflammatory response in the lungs. This response gives rise to fibrin deposition in the microvasculature and alveoli of the lungs. Fibrin deposition in the microvasculature increases alveolar dead space, while fibrin deposition in alveoli causes shunting. We investigated whether prophylactic nebulised heparin could limit this form of lung injury. We undertook a single-centre double-blind randomised trial. Forty patients undergoing elective cardiac surgery with cardiopulmonary bypass were randomised to prophylactic nebulised heparin (50,000 U) or placebo. The primary endpoint was the change in arterial oxygen levels over the operative period. Secondary endpoints included end-tidal CO₂, the alveolar dead space fraction and bleeding complications. We found nebulised heparin did not improve arterial oxygen levels. Nebulised heparin was, however, associated with a lower alveolar dead space fraction (P <0.05) and lower tidal volumes at the end of surgery (P <0.01). Nebulised heparin was not associated with bleeding complications. In conclusion, prophylactic nebulised heparin did not improve oxygenation, but was associated with evidence of better alveolar perfusion and CO₂elimination at the end of surgery.
Pongkan, Wanpitak; Chattipakorn, Siriporn C; Chattipakorn, Nipon
Testosterone is an anabolic steroid hormone, which is the major circulating androgen hormone in males. Testosterone levels decreasing below the normal physiological levels lead to a status known as androgen deficiency. Androgen deficiency has been shown to be a major risk factor in the development of several disorders, including obesity, metabolic syndrome, and ischemic heart disease. In the past decades, although several studies from animal models as well as clinical studies demonstrated that testosterone exerted cardioprotection, particularly during ischemia-reperfusion (I/R) injury, other preclinical and clinical studies have shown an inverse relationship between testosterone levels and cardioprotective effects. As a result, the effects of testosterone replacement on the heart remain controversial. In this review, reports regarding the roles of testosterone replacement in the heart following I/R injury are comprehensively summarized and discussed. At present, it may be concluded that chronic testosterone replacement at a physiological dose demonstrated cardioprotective effects, whereas acute testosterone replacement can cause adverse effects in the I/R heart. © The Author(s) 2015.
Lenarczyk, Marek; Lam, Vy; Jensen, Eric; Fish, Brian L; Su, Jidong; Koprowski, Stacy; Komorowski, Richard A; Harmann, Leanne; Migrino, Raymond Q; Li, X Allen; Hopewell, John W; Moulder, John E; Baker, John E
The objective of this study was to determine whether radiation-induced injury to the heart after 10 Gy total body irradiation (TBI) is direct or indirect. Young male WAG/RijCmcr rats received a 10 Gy single dose using TBI, upper hemi-body (UHB) irradiation, lower hemi-body (LHB) irradiation, TBI with the kidneys shielded, or LHB irradiation with the intestines shielded. Age-matched, sham-irradiated rats served as controls. The lipid profile, kidney injury, heart and liver morphology and cardiac function were determined up to 120 days after irradiation. LHB, but not UHB irradiation, increased the risk factors for cardiac disease as well as the occurrence of cardiac and kidney injury in a way that was quantitatively and qualitatively similar to that observed after TBI. Shielding of the kidneys prevented the increases in risk factors for cardiac disease. Shielding of the intestines did not prevent the increases in risk factors for cardiac disease. There was no histological evidence of liver injury 120 days after irradiation. Injury to the heart from irradiation appears to be indirect, supporting the notion that injury to abdominal organs, principally the kidneys, is responsible for the increased risk factors for and the occurrence of cardiac disease after TBI and LHB irradiation. PMID:23919311
Lombi, Fernando; Muryan, Alexis; Canzonieri, Romina; Trimarchi, Hernán
Acute kidney injury in the critically ill represents an independent risk factor of morbidity and mortality in the short and long terms, with significant economic impacts in terms of public health costs. Currently its diagnosis is still based on the presence of oliguria and/or a gradual increase in serum creatinine, which make the diagnosis a delayed event and to detriment of the so-called 'therapeutic window'. The appearance of new biomarkers of acute kidney injury could potentially improve this situation, contributing to the detection of 'subclinical acute kidney injury', which could allow the precocious employment of multiple treatment strategies in order to preserve kidney function. However these new biomarkers display sensitive features that may threaten their full capacity of action, which focus specifically on their additional contribution in the early approach of the situation, given the lack of specific validated treatments for acute kidney injury. This review aims to analyze the strengths and weaknesses of these new tools in the early management of acute kidney injury.
Raupach, Jan Ferko, Alexander; Lojik, Miroslav; Krajina, Antonin; Harrer, Jan; Dominik, Jan
Our aim is to present midterm results after endovascular repair of acute and chronic blunt aortic injury. Between December 1999 and December 2005, 13 patients were endovascularly treated for blunt aortic injury. Ten patients, 8 men and 2 women, mean age 38.7 years, were treated for acute traumatic injury in the isthmus region of thoracic aorta. Stent-graftings were performed between the fifth hour and the sixth day after injury. Three patients (all males; mean age, 66 years; range, 59-71 years) were treated due to the presence of symptoms of chronic posttraumatic pseudoaneurysm of the thoracic aorta (mean time after injury, 29.4 years, range, 28-32). Fifteen stent-grafts were implanted in 13 patients. In the group with acute aortic injury one patient died due to failure of endovascular technique. Lower leg paraparesis appeared in one patient; the other eight patients were regularly followed up (1-72 months; mean, 35.6 months), without complications. In the group with posttraumatic pseudoaneurysms all three patients are alive. One patient suffered postoperatively from upper arm claudication, which was treated by carotidosubclavian bypass. We conclude that the endoluminal technique can be used successfully in the acute repair of aortic trauma and its consequences. Midterm results are satisfactory, with a low incidence of neurologic complications.
Rowe, Rachel K.; Striz, Martin; Bachstetter, Adam D.; Van Eldik, Linda J.; Donohue, Kevin D.; O'Hara, Bruce F.; Lifshitz, Jonathan
Objective Clinical observations report excessive sleepiness immediately following traumatic brain injury (TBI); however, there is a lack of experimental evidence to support or refute the benefit of sleep following a brain injury. The aim of this study is to investigate acute post-traumatic sleep. Methods Sham, mild or moderate diffuse TBI was induced by midline fluid percussion injury (mFPI) in male C57BL/6J mice at 9:00 or 21:00 to evaluate injury-induced sleep behavior at sleep and wake onset, respectively. Sleep profiles were measured post-injury using a non-invasive, piezoelectric cage system. In separate cohorts of mice, inflammatory cytokines in the neocortex were quantified by immunoassay, and microglial activation was visualized by immunohistochemistry. Results Immediately after diffuse TBI, quantitative measures of sleep were characterized by a significant increase in sleep (>50%) for the first 6 hours post-injury, resulting from increases in sleep bout length, compared to sham. Acute post-traumatic sleep increased significantly independent of injury severity and time of injury (9:00 vs 21:00). The pro-inflammatory cytokine IL-1β increased in brain-injured mice compared to sham over the first 9 hours post-injury. Iba-1 positive microglia were evident in brain-injured cortex at 6 hours post-injury. Conclusion Post-traumatic sleep occurs for up to 6 hours after diffuse brain injury in the mouse regardless of injury severity or time of day. The temporal profile of secondary injury cascades may be driving the significant increase in post-traumatic sleep and contribute to the natural course of recovery through cellular repair. PMID:24416145
Thompson, Karol L; Boitier, Eric; Chen, Tao; Couttet, Philippe; Ellinger-Ziegelbauer, Heidrun; Goetschy, Manuela; Guillemain, Gregory; Kanki, Masayuki; Kelsall, Janet; Mariet, Claire; de La Moureyre-Spire, Catherine; Mouritzen, Peter; Nassirpour, Rounak; O'Lone, Raegan; Pine, P Scott; Rosenzweig, Barry A; Sharapova, Tatiana; Smith, Aaron; Uchiyama, Hidefumi; Yan, Jian; Yuen, Peter S; Wolfinger, Russ
Extracellular microRNAs (miRNAs) represent a promising new source of toxicity biomarkers that are sensitive indicators of site of tissue injury. In order to establish reliable approaches for use in biomarker validation studies, the HESI technical committee on genomics initiated a multi-site study to assess sources of variance associated with quantitating levels of cardiac injury induced miRNAs in biofluids using RT-qPCR. Samples were generated at a central site using a model of acute cardiac injury induced in male Wistar rats by 0.5 mg/kg isoproterenol. Biofluid samples were sent to 11 sites for measurement of 3 cardiac enriched miRNAs (miR-1-3p, miR-208a-3p, and miR-499-5p) and 1 miRNA abundant in blood (miR-16-5p) or urine (miR-192-5p) by absolute quantification using calibration curves of synthetic miRNAs. The samples included serum and plasma prepared from blood collected at 4 h, urine collected from 6 to 24 h, and plasma prepared from blood collected at 24 h post subcutaneous injection. A 3 parameter logistic model was utilized to fit the calibration curve data and estimate levels of miRNAs in biofluid samples by inverse prediction. Most sites observed increased circulating levels of miR-1-3p and miR-208a-3p at 4 and 24 h after isoproterenol treatment, with no difference seen between serum and plasma. The biological differences in miRNA levels and sample type dominated as sources of variance, along with outlying performance by a few sites. The standard protocol established in this study was successfully implemented across multiple sites and provides a benchmark method for further improvements in quantitative assays for circulating miRNAs. Published by Oxford University Press on behalf of the Society of Toxicology 2016. This work is written by US Government employees and is in the public domain in the US.
Coelho, Filipe Utuari de Andrade; Watanabe, Mirian; Fonseca, Cassiane Dezoti da; Padilha, Katia Grillo; Vattimo, Maria de Fátima Fernandes
to evaluate the nursing workload in intensive care patients with acute kidney injury (AKI). A quantitative study, conducted in an intensive care unit, from April to August of 2015. The Nursing Activities Score (NAS) and Kidney Disease Improving Global Outcomes (KDIGO) were used to measure nursing workload and to classify the stage of AKI, respectively. A total of 190 patients were included. Patients who developed AKI (44.2%) had higher NAS when compared to those without AKI (43.7% vs 40.7%), p <0.001. Patients with stage 1, 2 and 3 AKI showed higher NAS than those without AKI. A relationship was identified between stage 2 and 3 with those without AKI (p = 0.002 and p <0.001). The NAS was associated with the presence of AKI, the score increased with the progression of the stages, and it was associated with AKI, stage 2 and 3. avaliar a carga de trabalho de enfermagem em pacientes de terapia intensiva com lesão renal aguda (LRA). estudo quantitativo, em Unidade de Terapia Intensiva, no período de abril a agosto de 2015. O Nursing Activities Score (NAS) e o Kidney Disease Improving Global Outcomes (KDIGO) foram utilizados para medir a carga de trabalho de enfermagem e classificar o estágio da LRA, respectivamente. foram incluídos 190 pacientes. Os pacientes que desenvolveram LRA (44,2%) possuíam NAS superiores quando comparados aos sem LRA (43,7% vs 40,7%), p<0,001. Os pacientes com LRA nos estágios 1, 2 e 3 de LRA demonstraram NAS superiores aos sem LRA, houve relação entre os estágios 2 e 3 com os sem LRA, p=0,002 e p<0,001. o NAS apresentou associação com a existência de LRA, visto que seu valor aumenta com a progressão dos estágios, tendo associação com os estágios 2 e 3 de LRA.
Rana, Indrajeetsinh; Velkoska, Elena; Patel, Sheila K; Burrell, Louise M; Charchar, Fadi J
Cardiovascular disease, including cardiac hypertrophy, is common in patients with kidney disease and can be partially attenuated using blockers of the renin-angiotensin system (RAS). It is unknown whether cardiac microRNAs contribute to the pathogenesis of cardiac hypertrophy or to the protective effect of RAS blockade in kidney disease. Using a subtotal nephrectomy rat model of kidney injury, we investigated changes in cardiac microRNAs that are known to have direct target genes involved in the regulation of apoptosis, fibrosis, and hypertrophy. The effect of treatment with the angiotensin-converting enzyme (ACE) inhibitor ramipril on cardiac microRNAs was also investigated. Kidney injury led to a significant increase in cardiac microRNA-212 and microRNA-132 expression. Ramipril reduced cardiac hypertrophy, attenuated the increase in microRNA-212 and microRNA-132, and significantly increased microRNA-133 and microRNA-1 expression. There was altered expression of caspase-9, B cell lymphoma-2, transforming growth factor-β, fibronectin 1, collagen type 1A1, and forkhead box protein O3, which are all known to be involved in the regulation of apoptosis, fibrosis, and hypertrophy in cardiac cells while being targets for the above microRNAs. ACE inhibitor treatment increased expression of microRNA-133 and microRNA-1. The inhibitory action of ACE inhibitor treatment on increased cardiac NADPH oxidase isoform 1 expression after subtotal nephrectomy surgery suggests that inhibition of oxidative stress is also one of mechanism of ACE inhibitor-mediated cardioprotection. These finding suggests the involvement of microRNAs in the cardioprotective action of ACE inhibition in acute renal injury, which is mediated through an inhibitory action on profibrotic and proapoptotic target genes and stimulatory action on antihypertrophic and antiapoptotic target genes.
Martínez, Gonzalo J; Robertson, Stacy; Barraclough, Jennifer; Xia, Qiong; Mallat, Ziad; Bursill, Christina; Celermajer, David S; Patel, Sanjay
Interleukin (IL)-1β, IL-18, and downstream IL-6 are key inflammatory cytokines in the pathogenesis of coronary artery disease. Colchicine is believed to block the NLRP3 inflammasome, a cytosolic complex responsible for the production of IL-1β and IL-18. In vivo effects of colchicine on cardiac cytokine release have not been previously studied. This study aimed to (1) assess the local cardiac production of inflammatory cytokines in patients with acute coronary syndromes (ACS), stable coronary artery disease and in controls; and (2) determine whether acute administration of colchicine inhibits their production. Forty ACS patients, 33 with stable coronary artery disease, and 10 controls, were included. ACS and stable coronary artery disease patients were randomized to oral colchicine treatment (1 mg followed by 0.5 mg 1 hour later) or no colchicine, 6 to 24 hours prior to cardiac catheterization. Blood samples from the coronary sinus, aortic root (arterial), and lower right atrium (venous) were collected and tested for IL-1β, IL-18, and IL-6 using ELISA. In ACS patients, coronary sinus levels of IL-1β, IL-18, and IL-6 were significantly higher than arterial and venous levels (P=0.017, <0.001 and <0.001, respectively). Transcoronary (coronary sinus-arterial) gradients for IL-1β, IL-18, and IL-6 were highest in ACS patients and lowest in controls (P=0.077, 0.033, and 0.014, respectively). Colchicine administration significantly reduced transcoronary gradients of all 3 cytokines in ACS patients by 40% to 88% (P=0.028, 0.032, and 0.032, for IL-1β, IL-18, and IL-6, respectively). ACS patients exhibit increased local cardiac production of inflammatory cytokines. Short-term colchicine administration rapidly and significantly reduces levels of these cytokines. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
Zhang, Zhengfeng; Zhou, Yue; Wang, Jian; Chu, Tongwei; Li, Changqing; Ren, Xianjun; Wang, Weidong
We retrospectively reviewed acute cervical cord injury after minor trauma in 10 patients with os odontoideum. Their clinical history, neurological symptoms, radiological investigations, follow-up period, American Spinal Injury Association impairment classification and motor score were reviewed. Before their traumatic injury, three patients were asymptomatic and seven reported myelopathic symptoms, including four patients with neck pain, two patients with unsteadiness and one patient with dizziness. Falls were the most common cause of injury (n=6), followed by minor motor vehicle accidents (n=3) and assault (n=1). MRI and dynamic cervical lateral radiographs showed that all patients had atlantoaxial instability and cord compression. Most patients had spinal cord thinning and hyperintensity on T2-weighted MRI. Spinal cord compression was posterior (n=5), or both anterior and posterior (n=5). All patients underwent posterior rigid screw fixation and fusion, including atlantoaxial fusion (n=8) and occipitocervical fusion (n=2). We conclude that patients with asymptomatic or myelopathic atlantoaxial instability secondary to os odontoideum are at risk for acute spinal cord injury after minor traumatic injury. Fixation and fusion should be undertaken as prophylactic treatment for patients at risk of developing myelopathy and to avoid the neurological deterioration associated with acute traumatic cervical cord injury. Copyright 2010 Elsevier Ltd. All rights reserved.
Incorvaia, Angelo N; Poulos, Despina M; Jones, Robert N; Tschirhart, James M
This is a case report of rare cardiac and abdominal organ injuries sustained by an innocent bystander from a New Year's Eve celebratory gun shooting. The force and velocity of a projectile fired into the air as it ascends and returns to earth, along with its potential for bodily injury will be reviewed.
To review: a) the role of extravascular fibrin deposition in the pathogenesis of acute lung injury; b) the abnormalities in the coagulation and fibrinolysis pathways that promote fibrin deposition in the acutely injured lung; and c) the pathways that contribute to the regulation of the fibrinolytic system via the lung epithelium, including newly recognized posttranscriptional and urokinase-dependent pathways. Another objective was to determine how novel anticoagulant or fibrinolytic strategies may be used to protect against acute inflammation or accelerated fibrosis in acute lung injury. Published medical literature. Alveolar fibrin deposition is characteristic of diverse forms of acute lung injury. Intravascular thrombosis or disseminated intravascular coagulation can also occur in the acutely injured lung. Extravascular fibrin deposition promotes lung dysfunction and the acute inflammatory response. In addition, transitional fibrin in the alveolar compartment undergoes remodeling leading to accelerated pulmonary fibrosis similar to the events associated with wound healing, or desmoplasia associated with solid neoplasms. In acute lung injury, alveolar fibrin deposition is potentiated by consistent changes in endogenous coagulation and fibrinolytic pathways. Procoagulant activity is increased in conjunction with depression of fibrinolytic activity in the alveolar compartment. Initiation of the procoagulant response occurs as a result of local overexpression of tissue factor associated with factor VII. Depression of fibrinolytic activity occurs as a result of inhibition of urokinase plasminogen activator (uPA) by plasminogen activators, or series inhibition of plasmin by antiplasmins. Locally increased amplification of plasminogen activator inhibitor-1 (PAI-1) is largely responsible for this fibrinolytic defect. Newly described pathways by which lung epithelial cells regulate expression of uPA, its receptor uPAR, and PAI-1 at the posttranscriptional level have been
Tsukada, K; Azuhata, H; Katoh, H; Kuwano, H
The herbicide, pendimethalin, is used worldwide, but its acute toxicity is not yet widely known. There have been some reported acute pendimethalin poisoning cases in humans and most of them intentionally ingested the concentrated formulation. We describe a 73-year-old man who developed corrosive gastroduodenal injury after accidental ingestion of the diluted (300 times with water) pendimethalin formulation. He had a history of reflux oesophagitis and had been taking omeprazol (10 mg/day) for a year. He consumed alcohol two hours after the accidental ingestion and then had nausea and epigastric pain. Endoscopy performed three days post-exposure revealed gastroduodenal injury. As he had consumed alcohol every day for years and had no history of gastroduodenal ulcer, the accidental ingestion may be associated with this injury. He was successfully treated by increasing his dosage of omeprazol (20 mg/day) for two weeks. This case indicates that ingestion of a small quantity of pendimethalin can provoke gastroduodenal injury.
Kromer, P; Röcker, K; Sommer, A; Baur, H; Konstantinidis, L; Gollhofer, A; Südkamp, N P; Hirschmüller, A
Although paracycling is a growing discipline in high level competitive sports as well as in posttraumatic rehabilitation, epidemiological data of resulting injuries is still missing. Therefore, 19 athletes of the German national paracycling team were asked about their injuries during the 2008 season using a standardized questionnaire. Overall, 18 (94.7 %) of 19 athletes reported overuse injuries; most commonly localized at the back (83.3 %), neck/shoulder (77.8 %), knee (50 %), groin/buttock (50 %) and hands/wrists (38.9 %). Altogether, 18 accidents were registered, corresponding to an injury rate of 0,95 acute injuries per athlete per year (0,07 / 1000 km). The most common acute injuries were abrasions (69.2 %) and contusions (61.5 %), whereas fractures were stated only twice (11.8 %). The anatomical distribution of overuse injuries in disabled cyclists confirms the results of studies in able-bodied cycling, although the incidences in low-back pain and neck/shoulder pain is clearly higher in disabled cycling, as well as the rate of traumatic injuries.
Itoh, Takefumi; Obata, Hiroaki; Murakami, Shinsuke; Hamada, Kaoru; Kangawa, Kenji; Kimura, Hiroshi; Nagaya, Noritoshi
Adrenomedullin (AM), an endogenous peptide, has been shown to have a variety of protective effects on the cardiovascular system. However, the effect of AM on acute lung injury remains unknown. Accordingly, we investigated whether AM infusion ameliorates lipopolysaccharide (LPS)-induced acute lung injury in rats. Rats were randomized to receive continuous intravenous infusion of AM (0.1 microg x kg(-1) x min(-1)) or vehicle through a microosmotic pump. The animals were intratracheally injected with either LPS (1 mg/kg) or saline. At 6 and 18 h after intratracheal instillation, we performed histological examination and bronchoalveolar lavage and assessed the lung wet/dry weight ratio as an index of acute lung injury. Then we measured the numbers of total cells and neutrophils and the levels of tumor necrosis factor (TNF)-alpha and cytokine-induced neutrophil chemoattractant (CINC) in bronchoalveolar lavage fluid (BALF). In addition, we evaluated BALF total protein and albumin levels as indexes of lung permeability. LPS instillation caused severe acute lung injury, as indicated by the histological findings and the lung wet/dry weight ratio. However, AM infusion attenuated these LPS-induced abnormalities. AM decreased the numbers of total cells and neutrophils and the levels of TNF-alpha and CINC in BALF. AM also reduced BALF total protein and albumin levels. In addition, AM significantly suppressed apoptosis of alveolar wall cells as indicated by cleaved caspase-3 staining. In conclusion, continuous infusion of AM ameliorated LPS-induced acute lung injury in rats. This beneficial effect of AM on acute lung injury may be mediated by inhibition of inflammation, hyperpermeability, and alveolar wall cell apoptosis.
Engoren, Milo; Brown, Russell R; Dubovoy, Anna
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.
Hull, Travis D; Bolisetty, Subhashini; DeAlmeida, Angela C; Litovsky, Silvio H; Prabhu, Sumanth D; Agarwal, Anupam; George, James F
The protective effect of heme oxygenase-1 (HO-1) expression in cardiovascular disease has been previously demonstrated using transgenic animal models in which HO-1 is constitutively overexpressed in the heart. However, the temporal requirements for protection by HO-1 induction relative to injury have not been investigated, but are essential to employ HO-1 as a therapeutic strategy in human cardiovascular disease states. Therefore, we generated mice with cardiac-specific, tamoxifen (TAM)-inducible overexpression of a human HO-1 (hHO-1) transgene (myosin heavy chain (MHC)-HO-1 mice) by breeding mice with cardiac-specific expression of a TAM-inducible Cre recombinase (MHC-Cre mice), with mice containing an hHO-1 transgene preceded by a floxed-stop signal. MHC-HO-1 mice overexpress HO-1 mRNA and the enzymatically active protein following TAM administration (40 mg/kg body weight on 2 consecutive days). In MHC-Cre controls, TAM administration leads to severe, acute cardiac toxicity, cardiomyocyte necrosis, and 80% mortality by day 3. This cardiac toxicity is accompanied by a significant increase in inflammatory cells in the heart that are predominantly neutrophils. In MHC-HO-1 mice, HO-1 overexpression ameliorates the depression of cardiac function and high mortality rate observed in MHC-Cre mice following TAM administration and attenuates cardiomyocyte necrosis and neutrophil infiltration. These results highlight that HO-1 induction is sufficient to prevent the depression of cardiac function observed in mice with TAM-inducible Cre recombinase expression by protecting the heart from necrosis and neutrophil infiltration. These findings are important because MHC-Cre mice are widely used in cardiovascular research despite the limitations imposed by Cre-induced cardiac toxicity, and also because inflammation is an important pathological component of many human cardiovascular diseases.
Bagheri, Fereshte; Khori, Vahid; Alizadeh, Ali Mohammad; Khalighfard, Solmaz; Khodayari, Saeed; Khodayari, Hamid
Reperfusion injury is an inherent response to the restoration of blood flow after ischemia. It is a complex process involving numerous mechanisms occurring in the intracellular and extracellular environments, and it is mediated in part by reactive oxygen species (ROS). The imbalance between the cellular formation of free radicals and cells' capacity to defend against them can cause cardiac tissue injuries. In this context, ROS play an essential role in both the organ injury and repair processes. After reperfusion, infiltration into the myocardium of inflammatory leucocytes, such as macrophages and neutrophils, causes further ROS production beyond the initiation of the inflammatory cascade. In this case, ROS overproduction is crucial in cardiac injury, and it can increase the complications related to cardiac reperfusion. In myocardial tissue, ROS can be produced from several sources, such as xanthine oxidase, cytochrome oxidase, cyclooxygenase, mediated unsaturated fatty acid oxidation, oxidation of catecholamines, mitochondrial oxidation, activation of leukocyte nicotinamide adenine dinucleotide phosphate oxidase, iron release, and reduction-oxidation reaction cycling; all of these sources reduce molecular oxygen in the reperfused myocardium. This review discusses about the molecular and therapeutic aspects of cardiac-reperfusion injuries generated by ROS. Experimental and clinical evidence with respect to the use of ischemic preconditioning, Ca(2+), nitric oxide, and conventional antioxidants in cardiac-reperfusion injury are summarized, and causal therapy approaches with various antioxidants are discussed.
van Waes, Judith A R; Grobben, Remco B; Nathoe, Hendrik M; Kemperman, Hans; de Borst, Gert Jan; Peelen, Linda M; van Klei, Wilton A
To evaluate the role of routine troponin surveillance in patients undergoing major noncardiac surgery, unblinded screening with cardiac consultation per protocol was implemented at a tertiary care center. In this study, we evaluated 1-year mortality, causes of death, and consequences of cardiac consultation of this protocol. This observational cohort included 3224 patients ≥60 years old undergoing major noncardiac surgery. Troponin I was measured routinely on the first 3 postoperative days. Myocardial injury was defined as troponin I >0.06 μg/L. Regression analysis was used to determine the association between myocardial injury and 1-year mortality. The causes of death, the diagnoses of the cardiologists, and interventions were determined for different levels of troponin elevation. Postoperative myocardial injury was detected in 715 patients (22%) and was associated with 1-year all-cause mortality (relative risk [RR] 1.4, P = 0.004; RR 1.6, P < 0.001; and RR 2.2, P < 0.001 for minor, moderate, and major troponin elevation, respectively). Cardiac death within 1 year occurred in 3%, 5%, and 11% of patients, respectively, in comparison with 3% of the patients without myocardial injury (P = 0.059). A cardiac consultation was obtained in 290 of the 715 patients (41%). In 119 (41%) of these patients, the myocardial injury was considered to be attributable to a predisposing cardiac condition, and in 111 patients (38%), an intervention was initiated. Postoperative myocardial injury was associated with an increased risk of 1-year all-cause but not cardiac mortality. A cardiac consultation with intervention was performed in less than half of these patients. The small number of interventions may be explained by a low suspicion of a cardiac etiology in most patients and lack of consensus for standardized treatment in these patients.
Radhakrishnan, H; Gopi, M; Arumugam, A
Ammonium dichromate is an inorganic compound frequently used in screen and color printing. Being a strong oxidizing agent, it causes oxygen free radical injury resulting in organ failure. We report a 25-year-old female who presented with acute kidney injury after consumption of ammonium dichromate. She was managed successfully with hemodialysis and supportive measures. This case is reported to highlight the toxicity of ammonium dichromate.
Hartings, Jed A
Spreading depolarizations are unique in being discrete pathologic entities that are well characterized experimentally and also occur commonly in patients with substantial acute brain injury. Here, we review essential concepts in depolarization monitoring, highlighting its clinical significance, interpretation, and future potential. Cortical lesion development in diverse animal models is mediated by tissue waves of mass spreading depolarization that cause the toxic loss of ion homeostasis and limit energy substrate supply through associated vasoconstriction. The signatures of such deterioration are observed in electrocorticographic recordings from perilesional cortex of patients with acute stroke or brain trauma. Experimental work suggests that depolarizations are triggered by energy supply-demand mismatch in focal hotspots of the injury penumbra, and depolarizations are usually observed clinically when other monitoring variables are within recommended ranges. These results suggest that depolarizations are a sensitive measure of relative ischemia and ongoing secondary injury, and may serve as a clinical guide for personalized, mechanistically targeted therapy. Both existing and future candidate therapies offer hope to limit depolarization recurrence. Electrocorticographic monitoring of spreading depolarizations in patients with acute brain injury provides a sensitive measure of relative energy shortage in focal, vulnerable brains regions and indicates ongoing secondary damage. Depolarization monitoring holds potential for targeted clinical trial design and implementation of precision medicine approaches to acute brain injury therapy.
Wang, Yunru; Xu, Peng; Wang, Yang; Liu, Haiyan; Zhou, Yuwen; Cao, Xuebin
Objective. To investigate the protection of salidroside of the heart against acute exhaustive injury and its mechanism of antioxidative stress and MAPKs signal transduction. Method. Adult male SD rats were divided into four groups randomly. Cardiomyocytes ultrastructure was observed by optical microscopy and transmission electron microscopy. The contents of CK, CK-MB, LDH, MDA, and SOD were determined by ELISA method, and the phosphorylation degrees of ERK and p38 MAPK were assayed by Western blotting. Cardiac function of isolated rat heart ischemia/reperfusion was detected by Langendorff technique. Results. Salidroside reduced the myocardium ultrastructure injury caused by exhaustive swimming, decreased the contents of CK, CK-MB, and LDH, improved the LVDP, ±LV dp/dt max under the basic condition, reduced the content of MDA and the phosphorylation degree of p38 MAPK, and increased the content of SOD and the phosphorylation degree of ERK in acute exhaustive rats. Conclusion. Salidroside has the protection of the heart against acute exhaustive injury. The cardioprotection is mainly mediated by antioxidative stress and MAPKs signal transduction through reducing the content of MDA, increasing the content of SOD, and increasing p-ERK and decreasing p-p38 protein expressions in rat myocardium, which might be the mechanisms of the cardioprotective effect of salidroside. PMID:24454984
Fujita, Yoshiro; Hasegawa, Midori; Nabeshima, Kuihiro; Tomita, Makoto; Murakami, Kazutaka; Nakai, Shigeru; Yamakita, Takashi; Matsunaga, Kayoko
Drug rash with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS), is a severe adverse drug reaction affecting multiple organs caused by drug treatment. The current report describes a man who was prescribed zonisamide for epilepsy and subsequently developed widespread skin rash, acute kidney injury, high-grade fever, eosinophilia, liver dysfunction, lymphadenopathy and an increase in antihuman herpesvirus-6 immunoglobulin G titer. Hypersensitivity to zonisamide was confirmed by the skin patch test. Based on these findings, the patient was diagnosed with DRESS/DIHS caused by zonisamide. This is the first report of acute kidney injury due to zonisamide-induced DRESS/DIHS.
Thibault-Halman, Ginette; Casha, Steven; Singer, Shirley
Abstract A systematic review of the literature was performed to address pertinent clinical questions regarding nutritional management in the setting of acute spinal cord injury (SCI). Specific metabolic challenges are present following spinal cord injury. The acute stage is characterized by a reduction in metabolic activity, as well as a negative nitrogen balance that cannot be corrected, even with aggressive nutritional support. Metabolic demands need to be accurately monitored to avoid overfeeding. Enteral feeding is the optimal route following SCI. When oral feeding is not possible, nasogastric, followed by nasojejunal, then by percutaneous endoscopic gastrostomy, if necessary, is suggested. PMID:20373845
Sadeghi, Mohsen Mirmohammad; Gharipour, Mojgan; Nilforoush, Peiman; Shamsolkotabi, Hamid; Sadeghi, Hamid Mirmohammad; Kiani, Amjad; Sadeghi, Pouya Mirmohammad; Farahmand, Niloufar
There is limited data about the influence of timing of cardiac surgery in relation to diagnostic angiography and/or the impact of the amount of contrast media used during angiography on the occurance of acute renal failure (ARF). Therefore, in the present study the effect of the time interval between diagnostic angiography and cardiac surgery and also the amount of contrast media used during the diagnostic procedure on the incidence of ARF after cardiac surgery was investigated. Data of 1177 patients who underwent different types of cardiac surgeries after cardiac catheterization were prospectively examined. The influence of time interval between cardiac catheterization and surgery as well as the amount of contrast agent on postoperative ARF were assessed using multivariable logistic regression. The patients who progressed to ARF were more likely to have received a higher dose of contrast agent compared to the mean dose. However, the time interval between cardiac surgery and last catheterization was not significantly different between the patients with and without ARF (p = 0.05). Overall, postoperative peak creatinine was highest on day 0, then decreased and remained significantly unchanged after this period. Overall prevalence of acute renal failure during follow-up period had a changeable trend and had the highest rates in days 1 (53.57%) and 6 (52.17%) after surgery. Combined coronary bypass and valve surgery were the strongest predictor of postoperative ARF (OR: 4.976, CI = 1.613-15.355 and p = 0.002), followed by intra-aortic balloon pump insertion (OR: 6.890, CI = 1.482-32.032 and p = 0.009) and usage of higher doses of contrast media agent (OR: 1.446, CI = 1.033-2.025 and p = 0.031). Minimizing the amount of contrast agent has a potential role in reducing the incidence of postoperative ARF in patients undergoing cardiac surgery, but delaying cardiac surgery after exposure to these agents might not have this protective effect.
Singaravelu, K. P.; Saya, Rama Prakasha; Pandit, Vinay R.
In India, stab injury is not uncommon, but identifying potential life threatening conditions in the emergency room (ER) and initiating prompt treatment are challenging. This is a case report of a young patient who presented to the ER with assault injury to the chest and shock; timely extended focused assessment with sonography for trauma helped to fast-track the patient to the operating room. A brief review of diagnosis and management of penetrating cardiac injury is presented herewith. PMID:28400940
Korzick, D.H.; Lancaster, T.S.
Despite conflicting evidence for the efficacy of hormone replacement therapy in cardioprotection of postmenopausal women, numerous studies have demonstrated reductions in ischemia/reperfusion (I/R) injury following chronic or acute exogenous estradiol (E2) administration in adult male and female, gonad-intact and gonadectomized animals. It has become clear that ovariectomized adult animals may not accurately represent the combined effects of age and E2 deficiency on reductions in ischemic tolerance seen in the postmenopausal females. E2 is known to regulate the transcription of several cardioprotective genes. Acute, non-genomic E2 signaling can also activate many of the same signaling pathways recruited in cardioprotection. Alterations in cardioprotective gene expression or cardioprotective signal transduction are therefore likely to result within the context of aging and E2 deficiency, and may help explain the reduced ischemic tolerance and loss of cardioprotection in the senescent female heart. Quantification of the mitochondrial proteome as it adapts to advancing age and E2 deficiency may also represent a key experimental approach to uncover proteins associated with disruptions in cardiac signaling contributing to age-associated declines in ischemic tolerance. These alterations have important ramifications for understanding the increased morbidity and mortality due to ischemic cardiovascular disease seen in postmenopausal females. Functional perturbations that occur in mitochondrial respiration and Ca2+ sensitivity with age-associated E2 deficiency may also allow for the identification of alternative therapeutic targets for reducing I/R injury and treatment of the leading cause of death in postmenopausal women. PMID:23525672
Grissom, Colin K.; Morris, Alan H.; Lanken, Paul N.; Ancukiewicz, Marek; Orme, James F.; Schoenfeld, David A.; Thompson, B. Taylor
Objective To correlate physical examination findings, central venous pressure, fluid output, and central venous oxygen saturation with pulmonary artery catheter parameters. Design Retrospective study. Setting Data from the multicenter Fluid and Catheter Treatment Trial of the National Institutes of Health Acute Respiratory Distress Syndrome Network. Patients Five hundred thirteen patients with acute lung injury randomized to treatment with a pulmonary artery catheter. Interventions Correlation of physical examination findings (capillary refill time >2 secs, knee mottling, or cool extremities), central venous pressure, fluid output, and central venous oxygen saturation with parameters from a pulmonary artery catheter. Measurements We determined association of baseline physical examination findings and on-study parameters of central venous pressure and central venous oxygen saturation with cardiac index <2.5 L/min/m2 and mixed venous oxygen saturation <60%. We determined correlation of baseline central venous oxygen saturation and mixed venous oxygen saturation and predictive value of a low central venous oxygen saturation for a low mixed venous oxygen saturation. Measurements and Main Results Prevalence of cardiac index <2.5 and mixed venous oxygen saturation <60% was 8.1% and 15.5%, respectively. Baseline presence of all three physical examination findings had low sensitivity (12% and 8%), high specificity (98% and 99%), low positive predictive value (40% and 56%), but high negative predictive value (93% and 86%) for cardiac index <2.5 and mixed venous oxygen saturation <60%, respectively. Central venous oxygen saturation <70% predicted a mixed venous oxygen saturation <60% with a sensitivity 84%, specificity 70%, positive predictive value 31%, and negative predictive value of 96%. Low cardiac index correlated with cool extremities, high central venous pressure, and low 24-hr fluid output; and low mixed venous oxygen saturation correlated with knee mottling and
Grissom, Colin K; Morris, Alan H; Lanken, Paul N; Ancukiewicz, Marek; Orme, James F; Schoenfeld, David A; Thompson, B Taylor
To correlate physical examination findings, central venous pressure, fluid output, and central venous oxygen saturation with pulmonary artery catheter parameters. Retrospective study. Data from the multicenter Fluid and Catheter Treatment Trial of the National Institutes of Health Acute Respiratory Distress Syndrome Network. Five hundred thirteen patients with acute lung injury randomized to treatment with a pulmonary artery catheter. Correlation of physical examination findings (capillary refill time >2 secs, knee mottling, or cool extremities), central venous pressure, fluid output, and central venous oxygen saturation with parameters from a pulmonary artery catheter. We determined association of baseline physical examination findings and on-study parameters of central venous pressure and central venous oxygen saturation with cardiac index <2.5 L/min/m2 and mixed venous oxygen saturation <60%. We determined correlation of baseline central venous oxygen saturation and mixed venous oxygen saturation and predictive value of a low central venous oxygen saturation for a low mixed venous oxygen saturation. Prevalence of cardiac index <2.5 and mixed venous oxygen saturation <60% was 8.1% and 15.5%, respectively. Baseline presence of all three physical examination findings had low sensitivity (12% and 8%), high specificity (98% and 99%), low positive predictive value (40% and 56%), but high negative predictive value (93% and 86%) for cardiac index <2.5 and mixed venous oxygen saturation <60%, respectively. Central venous oxygen saturation <70% predicted a mixed venous oxygen saturation <60% with a sensitivity 84%,specificity 70%, positive predictive value 31%, and negative predictive value of 96%. Low cardiac index correlated with cool extremities, high central venous pressure, and low 24-hr fluid output; and low mixed venous oxygen saturation correlated with knee mottling and high central venous pressure, but these correlations were not found to be clinically useful. In
Bihari, Shailesh; Dixon, Dani-Louise; Lawrence, Mark D; Bersten, Andrew D
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.
Tang, Weibing; Wang, Zhi; Liu, Ye; Zhu, Jing
Acute respiratory distress syndrome is a life threatening respiratory condition characterized by breakdown of the alveolar-capillary barrier, leading to flooding of the alveolar space producing the classical chest radiograph of bilateral pulmonary infiltrates. In this study, we employed lung protective ventilation strategies in patients without acute lung injury (ALI) to determine whether mechanical ventilation with lower tidal volume would provide more clinical benefits to patients without ALI.
Honicker, Theresa; Holt, Karyn
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.
We have recently shown that episodic but not acute exposure to ozone or DEP induces vascular effects that are associated with the loss of cardiac mitochondrial phospholipid fatty acids (DEP 2.0 mg/m3 > ozone, 0.4 ppm). In this study we determined ozone and DEP-induced cardiac gen...
We have recently shown that episodic but not acute exposure to ozone or DEP induces vascular effects that are associated with the loss of cardiac mitochondrial phospholipid fatty acids (DEP 2.0 mg/m3 > ozone, 0.4 ppm). In this study we determined ozone and DEP-induced cardiac gen...
Zieg, Jakub; Hacek, Jaromir
Beta-lactam-associated acute tubulointerstitial nephritis (ATIN) is a rare condition in childhood. We report the case of an infant with penicillin-associated ATIN and concomitant acute pyelonephritis resulting in the development of severe acute kidney injury (AKI). The treatment consisted of penicillin suspension and appropriate AKI management, which required a short period of dialysis. Finally, full recovery and normalization of laboratory parameters occurred. We present here the first case of oral penicillin-associated ATIN in childhood.
Grifoni, Samira; Clark, Jeb S.; Csongradi, Eva; Maric, Christine; Juncos, Luis A.
Recent epidemiological reports showed that smoking has a negative impact on renal function and elevates the renal risk not only in the renal patient but perhaps also in the healthy population. Studies suggested that nicotine, a major tobacco alkaloid, links smoking to renal dysfunction. While several studies showed that smoking/chronic nicotine exposure exacerbates the progression of chronic renal diseases, its impact on acute kidney injury is virtually unknown. Here, we studied the effects of chronic nicotine exposure on acute renal ischemic injury. We found that chronic nicotine exposure increased the extent of renal injury induced by warm ischemia-reperfusion as evidenced by morphological changes, increase in plasma creatinine level, and kidney injury molecule-1 expression. We also found that chronic nicotine exposure elevated markers of oxidative stress such as nitrotyrosine as well as malondialdehyde. Interestingly, chronic nicotine exposure alone increased oxidative stress and injury in the kidney without morphological alterations. Chronic nicotine treatment not only increased reactive oxygen species (ROS) production and injury but also exacerbated oxidative stress-induced ROS generation through NADPH oxidase and mitochondria in cultured renal proximal tubule cells. The resultant oxidative stress provoked injury through JNK-mediated activation of the activator protein (AP)-1 transcription factor in vitro. This mechanism might exist in vivo as phosphorylation of JNK and its downstream target c-jun, a component of the AP-1 transcription factor, is elevated in the ischemic kidneys exposed to chronic nicotine. Our results imply that smoking may sensitize the kidney to ischemic insults and perhaps facilitates progression of acute kidney injury to chronic kidney injury. PMID:21511693
Arany, Istvan; Grifoni, Samira; Clark, Jeb S; Csongradi, Eva; Maric, Christine; Juncos, Luis A
Recent epidemiological reports showed that smoking has a negative impact on renal function and elevates the renal risk not only in the renal patient but perhaps also in the healthy population. Studies suggested that nicotine, a major tobacco alkaloid, links smoking to renal dysfunction. While several studies showed that smoking/chronic nicotine exposure exacerbates the progression of chronic renal diseases, its impact on acute kidney injury is virtually unknown. Here, we studied the effects of chronic nicotine exposure on acute renal ischemic injury. We found that chronic nicotine exposure increased the extent of renal injury induced by warm ischemia-reperfusion as evidenced by morphological changes, increase in plasma creatinine level, and kidney injury molecule-1 expression. We also found that chronic nicotine exposure elevated markers of oxidative stress such as nitrotyrosine as well as malondialdehyde. Interestingly, chronic nicotine exposure alone increased oxidative stress and injury in the kidney without morphological alterations. Chronic nicotine treatment not only increased reactive oxygen species (ROS) production and injury but also exacerbated oxidative stress-induced ROS generation through NADPH oxidase and mitochondria in cultured renal proximal tubule cells. The resultant oxidative stress provoked injury through JNK-mediated activation of the activator protein (AP)-1 transcription factor in vitro. This mechanism might exist in vivo as phosphorylation of JNK and its downstream target c-jun, a component of the AP-1 transcription factor, is elevated in the ischemic kidneys exposed to chronic nicotine. Our results imply that smoking may sensitize the kidney to ischemic insults and perhaps facilitates progression of acute kidney injury to chronic kidney injury.
Sánchez-de-la-Torre, Alicia; Soler, Xavier; Barbé, Ferran; Florés, Marina; Maisel, Alan; Malhotra, Atul; Rue, Montserrat; Bertran, Sandra; Aldomá, Albina; Worner, Fernando; Valls, Joan; Lee, Chi-Hang; Turino, Cecilia; Galera, Estefanía; de Batlle, Jordi; Sánchez-de-la-Torre, Manuel
An analysis of cardiac injury markers in patients with OSA who sustain an episode of acute coronary syndrome (ACS) may contribute to a better understanding of the interactions and impact of OSA in subjects with ACS. We compared peak cardiac troponin I (cTnI) levels in patients with OSA and patients without OSA who were admitted for ACS. Blood samples were collected every 6 hours from the time of admission until two consecutive assays showed a downward trend in the cTnI assay. The highest value obtained defined the peak cTnI value, which provides an estimate of infarct size. We included 89 patients with OSA and 38 patients without OSA with an apnea-hypopnea index of a median of 32 (interquartile range [IQR], 20.8-46.6/h and 4.8 [IQR, 1.6-9.6]/h, respectively. The peak cTnI value was significantly higher in patients without OSA than in patients with OSA (median, 10.7 ng/mL [IQR, 1.78-40.1 ng/mL] vs 3.79 ng/mL [IQR, 0.37-24.3 ng/mL]; P = .04). The multivariable linear regression analysis of the relationship between peak cTnI value and patient group, age, sex, and type of ACS showed that the presence or absence of OSA significantly contributed to the peak cTnI level, which was 54% lower in patients with OSA than in those without OSA. The results of this study suggest that OSA has a protective effect in the context of myocardial infarction and that patients with OSA may experience less severe myocardial injury. The possible role of OSA in cardioprotection should be explored in future studies. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
Ortiz, Alberto; Justo, Pilar; Sanz, Ana; Lorz, Corina; Egido, Jesús
Recent research has shown that apoptosis and its regulatory mechanisms contribute to cell number regulation in acute renal failure. Acute tubular necrosis is the most frequent form of parenchymal acute renal failure. The main causes are ischemia-reperfusion, sepsis and nephrotoxic drugs. Exogenous factors such as nephrotoxic drugs and bacterial products, and endogenous factors such as lethal cytokines promote tubular cell apoptosis. Such diverse stimuli engage intracellular death pathways that in some cases are stimulus-specific. We now review the role of apoptosis in acute renal failure, the potential molecular targets of therapeutic intervention, the therapeutic weapons to modulate the activity of these targets and the few examples of therapeutic intervention on apoptosis.
Amritsar, Jeetender; Stiharu, Ion G.; Packirisamy, Muthukumaran; Balagopal, Ganesharam; Li, Xing
Biomedical applications of MOEMS are limited only by the mankind imagination. Precision measurements on minute amounts of biological material could be performed by optical means with a remarkable accuracy. Although available in medical laboratories for general purposes, such analyzers are making their way directly to the users in the form of dedicated equipment. Such an example is a test kit to detect the existence of cardiac enzymes in the blood stream. Apart from the direct users, the medical personnel will make use of such tools given the practicality of the kit. In a large proportion of patients admitted to the hospital suspected of Acute Myocardial Infarction (AMI), the symptoms and electrocardiographic changes are inconclusive. This necessitates the use of biochemical markers of myocardial damage for correct exclusion or conformation of AMI. In this study the concept of MOEMS is applied for the detection of enzyme reaction, in which glass spectrums are scanned optically when enzyme molecules adsorb on their surface. This paper presents the optical behavior of glass spectrums under Horseradish Peroxide (HRP) enzyme reaction. The reported experimental results provide valuable information that will be useful in the development of biosensors for enzymatic detection. This paper also reports the dynamic behavior of different glass spectrums.
Wu, Wenyue; Chang, Shiyang; Wu, Qiong; Xu, Zhifang; Wang, Peina; Li, Yaru; Yu, Peng; Gao, Guofen; Shi, Zhenhua; Duan, Xianglin; Chang, Yan-Zhong
Mitochondrial ferritin (FtMt) is a mitochondrially localized protein possessing ferroxidase activity and the ability to store iron. FtMt overexpression in cultured cells protects against oxidative damage by sequestering redox-active, intracellular iron. Here, we found that acute exhaustive exercise significantly increases FtMt expression in the murine heart. FtMt gene disruption decreased the exhaustion exercise time and altered heart morphology with severe cardiac mitochondrial injury and fibril disorganization. The number of apoptotic cells as well as the levels of apoptosis-related proteins was increased in the FtMt−/− mice, though the ATP levels did not change significantly. Concomitant to the above was a high ‘uncommitted' iron level found in the FtMt−/− group when exposed to acute exhaustion exercise. As a result of the increase in catalytic metal, reactive oxygen species were generated, leading to oxidative damage of cellular components. Taken together, our results show that the absence of FtMt, which is highly expressed in the heart, increases the sensitivity of mitochondria to cardiac injury via oxidative stress. PMID:27853170
Strecker, Thomas; Bertz, Simone; Wachter, David Lukas; Weyand, Michael; Agaimy, Abbas
Acute aortic dissection is a life-threatening condition mainly caused by hypertension, atherosclerotic disease and other degenerative diseases of the connective tissue of the aortic wall. Mesothelial/monocytic incidental cardiac excrescences (cardiac MICE) is a rare benign reactive tumor-like lesion composed of admixture of histiocytes, mesothelial cells, and inflammatory cells set within a fibrinous meshwork without a vascular network or supporting stroma. Cardiac MICE occurring in association with aortic dissection is exceptionally rare (only one such case reported to date). We herein report on the surgical repair of two Stanford type A aortic dissections caused by idiopathic giant cell aortitis in a 66-year-old-woman and by atherosclerotic disease in a 58-year-old-man, respectively. In both cases, the dissections could be visualized via computed tomography. Histopathology showed cardiac incidental MICE within the external aortic wall near the pericardial surface which was confirmed by immunohistochemistry. PMID:26097568
Langham, J; Goldfrad, C; Teasdale, G; Shaw, D; Rowan, K
Acute traumatic brain injury is a major cause of death and disability. Calcium channel blockers (calcium antagonists) have been used in an attempt to prevent cerebral vasospasm after injury, maintain blood flow to the brain, and so prevent further damage. To estimate the effects of calcium channel blockers in patients with acute traumatic brain injury, and in a subgroup of brain injury patients with traumatic subarachnoid haemorrhage. Handsearching and electronic searching for randomised controlled trials. Randomised controlled trials in patients with all levels of severity of clinically diagnosed acute traumatic brain injury. Two reviewers independently assessed the identified studies for eligibility and extracted data from each study. Summary odds ratios were calculated using the Mantel-Haenszel method. Six RCTs were identified as eligible for inclusion in the systematic review. The effect of calcium channel blockers on the risk of death was reported in five of the RCTs. The pooled odds ratio (OR) for the five studies was 0.91 (95% confidence interval [95%CI] 0.70-1.17). For the four RCTs that reported death and severe disability (unfavourable outcome), the pooled odds ratio was 0.85 (95%CI 0.68-1.07). In the two RCTs which reported the risk of death in a subgroup of traumatic subarachnoid haemorrhage patients, the pooled odds ratio was 0.59 (95%CI 0.37-0.94). Three RCTs reported death and severe disability as an outcome in this subgroup, and the pooled odds ratio was 0.67 (95%CI 0.46-0.98). This systematic review of randomised controlled trials of calcium channel blockers in acute traumatic head injury patients shows that considerable uncertainty remains over their effects. The effect of nimodipine in a subgroup of brain injury patients with subarachnoid haemorrhage shows a beneficial effect, though the increase in adverse reactions suffered by the intervention group may mean that the drug is harmful for some patients.
Diabetes combined with cardiomyopathy is considered as an essential complication, showing diastolic persistently and causing cardiac injury, which is linked to fibrosis progression and inflammation response. Fibrosis and inflammation response are two markers for cardiomyopathy. Liquiritigenin is a flavanone, isolated from Radix glycyrrhiza, which exhibits various biological properties, including anti-cancer and anti-inflammatory activities. Here, in our study, the protective effects and anti-inflammatory activity of liquiritigenin were explored in mice and cardiac muscle cells treated by fructose to reveal the possible mechanism by which liquiritigenin attenuates cardiac injury. The mice were separated into five groups. The diabetic model of mouse was established with 30% high fructose feeding. Liquiritigenin dramatically reduced the lipid accumulation induced by high fructose diet. Compared to mice only treated with high fructose, mice in the presence of liquiritigenin after fructose feeding developed less cardiac fibrosis with lower levels of alpha smooth muscle-actin (α-SMA), Collagen type I, Collagen type II, TGF-β1 and Procol1a1. Additionally, liquiritigenin markedly down-regulated inflammatory cytokines secretion and phosphorylated NF-κB via inhibiting IKKα/IκBα signaling pathway. Our results indicate that liquiritigenin has a protective role in high fructose feeding-triggered cardiac injury through fibrosis and inflammation response suppression by inactivating NF-κB signaling pathway. Thus, liquiritigenin may be a potential candidate for diabetes-associated cardiac injury. Copyright © 2016. Published by Elsevier Masson SAS.
Kang, Eunjung; Cheong, Ka-Young; Lee, Min-Jeong; Kim, Seirhan; Shin, Gyu-Tae; Kim, Heungsoo; Park, In-Whee
Mushroom-related poisoning can cause acute kidney injury. Here we report a case of acute kidney injury after ingestion of Amanita punctata, which is considered an edible mushroom. Gastrointestinal symptoms occurred within 24 hours from the mushroom intake and were followed by an asymptomatic period, acute kidney injury, and elevation of liver and pancreatic enzymes. Kidney function recovered with supportive care. Nephrotoxic mushroom poisoning should be considered as a cause of acute kidney injury.
Kang, Eunjung; Cheong, Ka-Young; Lee, Min-Jeong; Kim, Seirhan; Shin, Gyu-Tae; Kim, Heungsoo; Park, In-Whee
Mushroom-related poisoning can cause acute kidney injury. Here we report a case of acute kidney injury after ingestion of Amanita punctata, which is considered an edible mushroom. Gastrointestinal symptoms occurred within 24 hours from the mushroom intake and were followed by an asymptomatic period, acute kidney injury, and elevation of liver and pancreatic enzymes. Kidney function recovered with supportive care. Nephrotoxic mushroom poisoning should be considered as a cause of acute kidney injury. PMID:26779427
Burns, Stephen P
Respiratory disorders are the leading cause of death for persons with both acute and chronic spinal cord injury (SCI), and much of the morbidity and mortality associated with respiratory disorders is related to acute respiratory infections. Pneumonia is the best recognized respiratory infection associated with mortality in this population. Recent evidence supports some management strategies that differ from those recommended for the general population. Upper respiratory tract infections and acute bronchitis may be precipitating factors in the development of pneumonia or ventilatory failure in patients with chronic SCI. This review emphasizes management principles for treatment and prevention of respiratory infections in persons with SCI.
Parikh, Chirag R; Puthumana, Jeremy; Shlipak, Michael G; Koyner, Jay L; Thiessen-Philbrook, Heather; McArthur, Eric; Kerr, Kathleen; Kavsak, Peter; Whitlock, Richard P; Garg, Amit X; Coca, Steven G
Clinical AKI, measured by serum creatinine elevation, is associated with long-term risks of adverse cardiovascular (CV) events and mortality in patients after cardiac surgery. To evaluate the relative contributions of urine kidney injury biomarkers and plasma cardiac injury biomarkers in adverse events, we conducted a multicenter prospective cohort study of 968 adults undergoing cardiac surgery. On postoperative days 1-3, we measured five urine biomarkers of kidney injury (IL-18, NGAL, KIM-1, L-FABP, and albumin) and five plasma biomarkers of cardiac injury (NT-proBNP, H-FABP, hs-cTnT, cTnI, and CK-MB). The primary outcome was a composite of long-term CV events or death, which was assessed via national health care databases. During a median 3.8 years of follow-up, 219 (22.6%) patients experienced the primary outcome (136 CV events and 83 additional deaths). Compared with patients without postsurgical AKI, patients who experienced AKI Network stage 2 or 3 had an adjusted hazard ratio for the primary composite outcome of 3.52 (95% confidence interval, 2.17 to 5.71). However, none of the five urinary kidney injury biomarkers were significantly associated with the primary outcome. In contrast, four out of five postoperative cardiac injury biomarkers (NT-proBNP, H-FABP, hs-cTnT, and cTnI) strongly associated with the primary outcome. Mediation analyses demonstrated that cardiac biomarkers explained 49% (95% confidence interval, 1% to 97%) of the association between AKI and the primary outcome. These results suggest that clinical AKI at the time of cardiac surgery is indicative of concurrent CV stress rather than an independent renal pathway for long-term adverse CV outcomes. Copyright © 2017 by the American Society of Nephrology.
Silva Júnior, Geraldo B; Abreu, Krasnalhia Lívia S; Mota, Rosa M S; Barreto, Adler G C; Araújo, Sônia M H A; Rocha, Hermano A L; Libório, Alexandre B; Daher, Elizabeth F
Acute kidney injury (AKI) is a common complication in leptospirosis. The aim of this study is to investigate the association between RIFLE and AKIN classifications with mortality in leptospirosis-associated AKI. A retrospective study was conducted in patients with leptospirosis admitted to tertiary hospitals in Brazil. The association between RIFLE and AKIN classifications with mortality was investigated. Univariate and multivariate analysis was performed to investigate risk factors for death. A total of 287 patients were included, with an average age of 37 ± 16 years, and 80.8% were male. Overall mortality was 13%. There was a significant association between these classifications and death. Among non-survivors, 86% were in the class 'failure' and AKIN 3. Increased mortality was observed according to the worse classifications: 'risk' (R; 2%), 'injury' (I; 8%) and 'failure' (F; 23%), as well as in AKIN 1 (2%), AKIN 2 (8%) and AKIN 3 (23%) (P < 0.0001). The worst classifications were significantly associated with death: RIFLE F (odds ratio = 11.6, P = 0.018) and AKIN 3 (odds ratio = 12.8, P = 0.013). Receiver-operator curve for patients with AKI showed high areas under the curve (0.71, 95% confidence interval = 0.67-0.74) for both RIFLE and AKIN classifications in determining the sensitivity for mortality. There is a significant association between RIFLE and AKIN classifications with mortality in patients with leptospirosis. Initiation of dialysis in patients with RIFLE F and AKIN 3 should always be considered. © 2011 The Authors. Nephrology © 2011 Asian Pacific Society of Nephrology.
Thompson, Jeremy; Hu, Ying; Lesnefsky, Edward J; Chen, Qun
Calpain 1 (CPN1) is a ubiquitous cysteine protease that exists in both cytosol and cardiac mitochondria. Mitochondrial CPN1 (mit-CPN1) is located in the intermembrane space and matrix. Activation of mit-CPN1 within the intermembrane space increases cardiac injury by releasing apoptosis-inducing factor from mitochondria during ischemia-reperfusion (IR). We asked if activation of mit-CPN1 is involved in mitochondrial injury during IR. MDL-28170 (MDL) was used to inhibit CPN1 in buffer-perfused hearts following 25-min ischemia and 30-min reperfusion. MDL treatment decreased the release of lactate dehydrogenase into coronary effluent compared with untreated hearts, indicating that inhibition of CPN1 decreases cardiac injury. MDL also prevented the cleavage of spectrin (a substrate of CPN1) in cytosol during IR, supporting that MDL treatment decreased cytosolic calpain activation. In addition, MDL markedly improved calcium retention capacity compared with untreated heart, suggesting that MDL treatment decreases mitochondrial permeability transition pore opening. In addition, we found that IR led to decreased complex I activity, whereas inhibition of mit-CPN1 using MDL protected complex I. Pyruvate dehydrogenase content was decreased following IR. However, pyruvate dehydrogenase content was preserved in MDL-treated mitochondria. Taken together, MDL treatment decreased cardiac injury during IR by inhibiting both cytosolic and mit-CPN1. Activation of mit-CPN1 increases cardiac injury during IR by sensitizing mitochondrial permeability transition pore opening and impairing mitochondrial metabolism through damage of complex I.
Thompson, Jeremy; Hu, Ying; Lesnefsky, Edward J.
Calpain 1 (CPN1) is a ubiquitous cysteine protease that exists in both cytosol and cardiac mitochondria. Mitochondrial CPN1 (mit-CPN1) is located in the intermembrane space and matrix. Activation of mit-CPN1 within the intermembrane space increases cardiac injury by releasing apoptosis-inducing factor from mitochondria during ischemia-reperfusion (IR). We asked if activation of mit-CPN1 is involved in mitochondrial injury during IR. MDL-28170 (MDL) was used to inhibit CPN1 in buffer-perfused hearts following 25-min ischemia and 30-min reperfusion. MDL treatment decreased the release of lactate dehydrogenase into coronary effluent compared with untreated hearts, indicating that inhibition of CPN1 decreases cardiac injury. MDL also prevented the cleavage of spectrin (a substrate of CPN1) in cytosol during IR, supporting that MDL treatment decreased cytosolic calpain activation. In addition, MDL markedly improved calcium retention capacity compared with untreated heart, suggesting that MDL treatment decreases mitochondrial permeability transition pore opening. In addition, we found that IR led to decreased complex I activity, whereas inhibition of mit-CPN1 using MDL protected complex I. Pyruvate dehydrogenase content was decreased following IR. However, pyruvate dehydrogenase content was preserved in MDL-treated mitochondria. Taken together, MDL treatment decreased cardiac injury during IR by inhibiting both cytosolic and mit-CPN1. Activation of mit-CPN1 increases cardiac injury during IR by sensitizing mitochondrial permeability transition pore opening and impairing mitochondrial metabolism through damage of complex I. PMID:26637561
Maiwall, Rakhi; Sarin, Shiv Kumar; Kumar, Suman; Jain, Priyanka; Kumar, Guresh; Bhadoria, Ajeet Singh; Moreau, Richard; Kedarisetty, Chandan Kumar; Abbas, Zaigham; Amarapurkar, Deepak; Bhardwaj, Ankit; Bihari, Chhagan; Butt, Amna Subhan; Chan, Albert; Chawla, Yogesh Kumar; Chowdhury, Ashok; Dhiman, RadhaKrishan; Dokmeci, Abdul Kadir; Ghazinyan, Hasmik; Hamid, Saeed Sadiq; Kim, Dong Joon; Komolmit, Piyawat; Lau, George K; Lee, Guan Huei; Lesmana, Laurentius A; Jamwal, Kapil; Mamun-Al-Mahtab; Mathur, Rajendra Prasad; Nayak, Suman Lata; Ning, Qin; Pamecha, Viniyendra; Alcantara-Payawal, Diana; Rastogi, Archana; Rahman, Salimur; Rela, Mohamed; Saraswat, Vivek A; Shah, Samir; Shiha, Gamal; Sharma, Barjesh Chander; Sharma, Manoj Kumar; Sharma, Kapil; Tan, Soek Siam; Chandel, Shivendra Singh; Vashishtha, Chitranshu; Wani, Zeeshan A; Yuen, Man-Fung; Yokosuka, Osamu; Duseja, Ajay; Jafri, Wasim; Devarbhavi, Harshad; Eapen, C E; Goel, Ashish; Sood, Ajit; Ji, Jia; Duan, Z; Chen, Y
There is limited data on predictors of acute kidney injury in acute on chronic liver failure. We developed a PIRO model (Predisposition, Injury, Response, Organ failure) for predicting acute kidney injury in a multicentric cohort of acute on chronic liver failure patients. Data of 2360 patients from APASL-ACLF Research Consortium (AARC) was analysed. Multivariate logistic regression model (PIRO score) was developed from a derivation cohort (n=1363) which was validated in another prospective multicentric cohort of acute on chronic liver failure patients (n=997). Factors significant for P component were serum creatinine[(≥2 mg/dL)OR 4.52, 95% CI (3.67-5.30)], bilirubin [(<12 mg/dL,OR 1) vs (12-30 mg/dL,OR 1.45, 95% 1.1-2.63) vs (≥30 mg/dL,OR 2.6, 95% CI 1.3-5.2)], serum potassium [(<3 mmol/LOR-1) vs (3-4.9 mmol/L,OR 2.7, 95% CI 1.05-1.97) vs (≥5 mmol/L,OR 4.34, 95% CI 1.67-11.3)] and blood urea (OR 3.73, 95% CI 2.5-5.5); for I component nephrotoxic medications (OR-9.86, 95% CI 3.2-30.8); for R component,Systemic Inflammatory Response Syndrome,(OR-2.14, 95% CI 1.4-3.3); for O component, Circulatory failure (OR-3.5, 95% CI 2.2-5.5). The PIRO score predicted acute kidney injury with C-index of 0.95 and 0.96 in the derivation and validation cohort. The increasing PIRO score was also associated with mortality (P<.001) in both the derivation and validation cohorts. The PIRO model identifies and stratifies acute on chronic liver failure patients at risk of developing acute kidney injury. It reliably predicts mortality in these patients, underscoring the prognostic significance of acute kidney injury in patients with acute on chronic liver failure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Joundi, Raed A; Rabinstein, Alejandro A; Nikneshan, Davar; Tu, Jack V; Fang, Jiming; Holloway, Robert; Saposnik, Gustavo
Cardiac arrest is a devastating complication of acute ischemic stroke, but little is known about its incidence and characteristics. We studied a large ischemic stroke inpatient population and compared patients with and without cardiac arrest. We studied consecutive patients from the Ontario Stroke Registry who had an ischemic stroke between July 2003 and June 2008 at 11 tertiary care stroke centers in Ontario. Multivariable analyses were used to determine independent predictors of cardiac arrest and associated outcomes. Adjusted survival curves were computed, and hazard ratios for mortality at 30 days and 1 year were determined for cardiac arrest and other major outcomes. Among the 9019 patients with acute ischemic stroke, 352 had cardiac arrest, for an overall incidence of 3.9%. In a sensitivity analysis with palliative patients removed, the incidence of cardiac arrest was 2.5%. Independent predictors of cardiac arrest were as follows: older age, greater stroke severity, preadmission dependence, and a history of diabetes, myocardial infarction, congestive heart failure, and atrial fibrillation. Systemic complications associated with cardiac arrest were as follows: myocardial infarction, pulmonary embolism, sepsis, gastrointestinal hemorrhage, and pneumonia. Patients with cardiac arrest had higher disability at discharge, and a markedly increased 30-day mortality of 82.1% compared with 9.3% without cardiac arrest. Cardiac arrest had a high incidence and was associated with poor outcomes after ischemic stroke, including multiple medical complications and very high mortality. Predictors of cardiac arrest identified in this study could help risk stratify ischemic stroke patients for cardiac investigations and prolonged cardiac monitoring. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.
Wohlauer, Max V; Sauaia, Angela; Moore, Ernest E; Burlew, Clay Cothren; Banerjee, Anirban; Johnson, Jeffrey
Despite improved resuscitation strategies, acute kidney injury (AKI) remains an important cause of morbidity and high resource use among severely injured patients. Thus, we conducted a comprehensive evaluation of the epidemiology and outcomes of early AKI among severely injured patients as well as its impact on the development of postinjury multiple organ failure (MOF). We queried our 17-year database of high-risk postinjury patients (Injury Severity Score >15, age >15 years, survival >48 hours, and no isolated head injury). MOF and AKI (creatinine >1.8 mg/dL) were defined by the Denver MOF score. Patients with documented preexisting renal, hepatic, cardiac, or pulmonary disease (120, 5%) were excluded, leaving 2157 for analysis. Early (day 2) AKI was evident in 2.13% of the patients and associated with a 78% MOF incidence and 27% mortality. Both rates were higher than those associated with early heart, lung, or liver failure. Early AKI is a harbinger of adverse outcome postinjury, outperforming hepatic, cardiac, or pulmonary dysfunction as a predictor of MOF and death. Prevention of early AKI and a better understanding of organ crosstalk may help reduce AKI-associated morbidity, mortality, and obligatory costs of this complication. I, prognostic study.
Thom, Vivien; Arumugam, Thiruma V.; Magnus, Tim; Gelderblom, Mathias
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
Nag, A.; Datta, J.; Das, A.; Agarwal, A. K.; Sinha, D.; Mondal, S.; Ete, T.; Chakraborty, A.; Ghosh, S.
Spiders of the Loxosceles species can cause dermonecrosis and acute kidney injury (AKI). Hemolysis, rhabdomyolysis and direct toxin-mediated renal damage have been postulated. There are very few reports of Loxoscelism from India. We report a case of AKI, hemolysis and a “gravitational” pattern of ulceration following the bite of the brown recluse spider (Loxosceles spp). PMID:25097339
Nag, A; Datta, J; Das, A; Agarwal, A K; Sinha, D; Mondal, S; Ete, T; Chakraborty, A; Ghosh, S
Spiders of the Loxosceles species can cause dermonecrosis and acute kidney injury (AKI). Hemolysis, rhabdomyolysis and direct toxin-mediated renal damage have been postulated. There are very few reports of Loxoscelism from India. We report a case of AKI, hemolysis and a "gravitational" pattern of ulceration following the bite of the brown recluse spider (Loxosceles spp).
Palkar, Atul Vijay; Mewada, Mayur; Thakur, Sonal; Shrivastava, Makardhwaj Sarvadaman
A 40-year-old female, presented with prerenal acute kidney injury secondary to diarrhoea. With appropriate hydration, she went into diuretic phase and subsequently developed hypokalemic quadriparesis with hypocalcaemic tetany due to hypomagnesemia and subclinical vitamin D deficiency. The patient improved with oral potassium, magnesium, calcium and vitamin D supplementation. PMID:22674589
Palkar, Atul Vijay; Mewada, Mayur; Thakur, Sonal; Shrivastava, Makardhwaj Sarvadaman
A 40-year-old female, presented with prerenal acute kidney injury secondary to diarrhoea. With appropriate hydration, she went into diuretic phase and subsequently developed hypokalemic quadriparesis with hypocalcaemic tetany due to hypomagnesemia and subclinical vitamin D deficiency. The patient improved with oral potassium, magnesium, calcium and vitamin D supplementation.
Ai, Qing; Ge, Pu; Dai, Jie; Liang, Tian-Cai; Yang, Qing; Lin, Ling; Zhang, Li
In this study, the effects of catalase (CAT) inhibitor aminotriazole (ATZ) on alcohol-induced acute liver injury were investigated to explore the potential roles of CAT in alcoholic liver injury. Acute liver injury was induced by intraperitoneal injection of alcohol in Sprague Dawley (SD) rats, and various doses of ATZ (100-400 mg/kg) or vehicle were administered intraperitoneally at 30 min before alcohol exposure. After 24 h of alcohol exposure, the levels of aspartate transaminase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) in plasma were determined. The degree of hepatic histopathological abnormality was observed by HE staining. The activity of hepatic CAT, hydrogen peroxide (H₂O₂) level and malondialdehyde (MDA) content in liver tissue were measured by corresponding kits. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in plasma were determined by ELISA method. The results showed that treatment with ATZ dose-dependently suppressed the elevation of ALT, AST and LDH levels induced by alcohol exposure, and that ATZ alleviated alcohol-induced histopathological alterations. Furthermore, ATZ inhibited the activity of CAT, reduced hepatic levels of H₂O₂and MDA in alcohol exposed rats. ATZ also decreased the levels of plasma TNF-α and IL-6 in rats with alcohol exposure. These results indicated that ATZ attenuated alcohol-induced acute liver injury in rats, suggesting that CAT might play important pathological roles in the pathogenesis of alcoholic liver injury.
Redelmeier, Donald A; Woodfine, Jason D; Thiruchelvam, Deva; Scales, Damon C
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.
Sahl, J D; Kelsh, M A; Haines, K D; Sands, F K; Kraus, J
This report provides estimates of incidence rates for acute work injuries for a well defined cohort of electric utility meter readers. Specifically, person-time rates by sex, age, and job experience are evaluated by part of body injured and type of injury. Meter readers experienced 731 acute lost time [11.1 per 100 person-work years; 95% confidence interval (CI) = 10.3-11.9] and 4,401 acute non-lost time (66.5 per 100 person-work years; 95% CI = 64.6-68.5) work injuries over the study period, 1980-1992. Women had nearly twice the lost time injury rate as men (17.5 vs 9.6 per 100 person-work years). There is an inverse relation between job experience and both lost time and non-lost time injuries. Although these data are limited to the electric utility industry, they may be relevant to occupations with similar tasks and environments, including residential gas and water supply industry meter readers and postal carriers.
Brough, David; Rothwell, Nancy J; Allan, Stuart M
What is the topic of this review? This review discusses the latest findings on the contribution of inflammation to brain injury, how inflammation is a therapeutic target, and details of recent and forthcoming clinical studies. What advances does it highlight? Here we highlight recent advances on the role and regulation of inflammasomes, and the latest clinical progress in targeting inflammation. Acute brain injury is one of the leading causes of mortality and disability worldwide. Despite this, treatments for acute brain injuries are limited, and there remains a massive unmet clinical need. Inflammation has emerged as a major contributor to non-communicable diseases, and there is now substantial and growing evidence that inflammation, driven by the cytokine interleukin-1 (IL-1), worsens acute brain injury. Interleukin-1 is regulated by large, multimolecular complexes called inflammasomes. Here, we discuss the latest research on the regulation of inflammasomes and IL-1 in the brain, preclinical efforts to establish the IL-1 system as a therapeutic target, and the promise of recent and future clinical studies on blocking the action of IL-1 for the treatment of brain injury. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.
Sinyakov, Michael S; Haimovich, Amihai; Avtalion, Ramy R
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.
Hinson, Jeremiah S; Ehmann, Michael R; Fine, Derek M; Fishman, Elliot K; Toerper, Matthew F; Rothman, Richard E; Klein, Eili Y
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
Zhang, Hao; Wang, Zheng; Feng, Shou-Jie; Xu, Lei; Shi, He-Xian; Chen, Li-Li; Yuan, Guang-Da; Yan, Wei; Zhuang, Wei; Zhang, Yi-Qian; Zhang, Zhong-Ming; Dong, Hong-Yan
Pigment epithelium-derived factor (PEDF) is a pleiotropic gene with anti-inflammatory, antioxidant and anti-angiogenic properties. However, recent reports about the effects of PEDF on cardiomyocytes are controversial, and it is not known whether and how PEDF acts to inhibit hypoxic or ischemic endothelial injury in the heart. In the present study, adult Sprague-Dawley rat models of acute myocardial infarction (AMI) were surgically established. PEDF-small interfering RNA (siRNA)-lentivirus (PEDF-RNAi-LV) or PEDF-LV was delivered into the myocardium along the infarct border to knockdown or overexpress PEDF, respectively. Vascular permeability, cardiomyocyte apoptosis, myocardial infarct size and animal cardiac function were analyzed. We also evaluated PEDF's effect on the suppression of the endothelial permeability and cardiomyocyte apoptosis under hypoxia in vitro. The results indicated that PEDF significantly suppressed the vascular permeability and inhibited hypoxia-induced endothelial permeability through PPARγ-dependent tight junction (TJ) production. PEDF protected cardiomyocytes against ischemia or hypoxia-induced cell apoptosis both in vivo and in vitro via preventing the activation of caspase-3. We also found that PEDF significantly reduced myocardial infarct size and enhanced cardiac function in rats with AMI. These data suggest that PEDF could protect cardiac function from ischemic injury, at least by means of reducing vascular permeability, cardiomyocyte apoptosis and myocardial infarct size.
Murakami, Kazunori; Enkhbaatar, Perenlei; Yu, Yong-Ming; Traber, Lillian D; Cox, Robert A; Hawkins, Hal K; Tompkins, Ronald G; Herndon, David; Traber, Daniel L
Thermal injury results in reduced plasma levels of arginine (Arg). With reduced Arg availability, NOS produces superoxide instead of NO. We hypothesized that Arg supplementation after burn and smoke inhalation (B + S) injury would attenuate the acute insult to the lungs and, thus, protect pulmonary function. Seventeen Suffolk ewes (n = 17) were randomly divided into three groups: (1) sham injury group (n = 6), (2) B + S injury plus saline treatment (n = 6), and (3) B + S injury plus L-ARG infusion at 57 mg.kg(-1).h(-1) (n = 5). Burn and smoke inhalation injury was induced by standardized procedures, including a 40% area full thickness flame burn combined with 48 breaths of smoke from burning cottons. All animals were immediately resuscitated by Ringer solution and supported by mechanical ventilation for 48 h, during which various variables of pulmonary function were monitored. The results demonstrated that Arg treatment attenuated the decline of plasma Arg concentration after B + S injury. A higher plasma Arg concentration was associated with a less decline in Pao2/Fio2 ratio and a reduced extent of airway obstruction after B + S injury. Histopathological examinations also indicated a remarkably reduced histopathological scores associated with B + S injury. Nitrotyrosine stain in lung tissue was positive after B + S injury, but was significantly reduced in the group with Arg. Therefore, L-Arg supplementation improved gas exchange and pulmonary function in ovine after B + S injury via its, at least in part, effect on reduction of oxidative stress through the peroxynitrite pathway.
Zager, Richard A; Johnson, Ali C M; Naito, Masayo; Lund, Steve R; Kim, Nayeon; Bomsztyk, Karol
Many of the studies of acute renal injury have been conducted in young mice usually during their rapid growth phase; yet, the impact of age or growth stage on the degree of injury is unknown. To address this issue, we studied three forms of injury (endotoxemic-, glycerol-, and maleate-induced) in mice ranging in age from adolescence (3 weeks) to maturity (16 weeks). The severity of injury within each model significantly correlated with weight and age. We also noticed a progressive age-dependent reduction in renal cholesterol content, a potential injury modifier. As the animals grew and aged they also exhibited stepwise decrements in the mRNAs of HMG CoA reductase and the low density lipoprotein receptor, two key cholesterol homeostatic genes. This was paralleled by decreased amounts of RNA polymerase II and the transcription factor SREBP1/2 at the reductase and lipoprotein receptor gene loci as measured by chromatin immunoprecipitation. Our study shows that the early phase of mouse growth can profoundly alter renal susceptibility to diverse forms of experimental acute renal injury.
Bornstein, N; Poon, W S
Stroke is one of the most devastating vascular diseases in the world as it is responsible for almost five million deaths per year. Almost 90% of all strokes are ischemic and mainly due to atherosclerosis, cardiac embolism and small-vessel disease. Intracerebral or subarachnoid hemorrhage can lead to hemorrhagic stroke, which usually has the poorest prognosis. Cerebrolysin is a peptide preparation which mimics the action of a neurotrophic factor, protecting stroke-injured neurons and promoting neuroplasticity and neurogenesis. Cerebrolysin has been widely studied as a therapeutic tool for both ischemic and hemorrhagic stroke, as well as traumatic brain injury. In ischemic stroke, Cerebrolysin given as an adjuvant therapy to antiplatelet and rheologically active medication resulted in accelerated improvement in global, neurological and motor functions, cognitive performance and activities of daily living. Cerebrolysin was also safe and well tolerated when administered in patients suffering from hemorrhagic stroke. Traumatic brain injury leads to transient or chronic impairments in physical, cognitive, emotional and behavioral functions. This is associated with deficits in the recognition of basic emotions, the capacity to interpret the mental states of others, and executive functioning. Pilot clinical studies with adjuvant Cerebrolysin in the acute and postacute phases of the injury have shown faster recovery, which translates into an earlier onset of rehabilitation and shortened hospitalization time.
Wang, Giueng-Chueng; Chi, Wei-Ming; Perng, Wan-Cherng; Huang, Kun-Lun
Body temperature is precisely regulated to maintain homeostasis in homeothermic animals. Although it remains unproved whether change of body temperature constitutes a beneficial or a detrimental component of the septic response, temperature control should be an important entity in septic experiments. We investigated the effect of body temperature control on the lipopolysaccharide (LPS)-induced lung injury. Acute lung injury in rats was induced by intratracheal spray of LPS and body temperature was either clamped at 37 degrees C for 5 hours or not controlled. The severity of lung injury was evaluated at the end of the experiment. Intratracheal administration of aerosolized LPS caused a persistent decline in body temperature and a significant lung injury as indicated by an elevation of protein-concentration and LDH activity in the bronchoalveolar lavage (BAL) fluid and wet/dry weight (W/D) ratio of lungs. Administration of LPS also caused neutrophil sequestration and lipid peroxidation in the lung tissue as indicated by increase in myeloperoxidase (MPO) activity and malondialdehyde (MDA) production, respectively. Control of body temperature at 37 degrees C after LPS (LPS/BT37, n = 11) significantly reduced acute lung injury as evidenced by decreases in BAL fluid protein concentration (983 +/- 189 vs. 1403 +/- 155 mg/L) and LDH activity (56 +/- 10 vs. 123 +/- 17 deltamAbs/min) compared with the LPS group (n = 11). Although the W/D ratio of lung and MDA level were lower in the rats received temperature control compared with those received LPS only, the differences were not statistically significant. Our results demonstrated that intratracheal administration of aerosolized LPS induced a hypothermic response and acute lung injury in rats and controlling body temperature at a normal range may alleviate the LPS-induced lung injury.
Wang, Wen-yao; Tang, Yi-da; Yang, Min; Cui, Cheng; Mu, Mu; Qian, Jie; Yang, Yue-jin
Previous studies have suggested that hypothyroidism correlated with coronary heart diseases (CHD) mortality in long-term cohort, but whether the thyroid function status is associated with myocardial injury in acute ST-elevation myocardial infarction (STEMI) has not been investigated sufficiently. Five hundred and eighty-two hospitalized patients from January 2010 to December 2011, with the diagnosis of STEMI, were enrolled in this study. All patients underwent testing for thyroid function status, cardiac troponin I (cTnI), cardiac enzymes, C-reactive protein (CRP). We investigated the association between thyroid hormone levels and cardiac markers (creatine kinase-MB and cTnI), and thus evaluated the potential role of thyroid function status in predicting the myocardial injury. There were 76 patients (13.06%) who had hypothyroidism including low-T3-syndrome (34 patients, 5.84%), subclinical hypothyroidism (28 patients, 4.81%) and clinical hypothyroidism (14 patients, 2.41%). After adjusting for conventional risk factors (age, gender, smoking, diabetes mellitus, dyslipidemia, hypertension), free triiodothyronine (FT3) was significantly and negatively correlated with log-CKMB (r = -0.244, P < 0.001) and log-cTnI (r = -0.290, P < 0.001), indicating that the lower thyroid hormone level correlates with the severer cardiac injury in STEMI patients. FT3 also had a moderate negative correlation with CRP (r = -0.475, P < 0.001), which might indicate that hypothyroidism may activate the inflammation response. No significant correlation was found between other thyroid parameters (TSH, FT4) and cardiac markers. As the lower FT3 level correlates with higher level of cardiac markers and lower left ventricular ejection fraction (LVEF), the hypothyroidism may be a predictor for myocardial injury in STEMI. And these results may warrant further study to investigate whether reversing the hypothyroidism could benefit the STEMI patients.
Fong, Daniel Tp; Chan, Yue-Yan; Mok, Kam-Ming; Yung, Patrick Sh; Chan, Kai-Ming
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 be
Fong, Daniel TP; Chan, Yue-Yan; Mok, Kam-Ming; Yung, Patrick SH; Chan, Kai-Ming
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
Keçeligil, Hasan Tahsin; Bahcivan, Muzaffer; Demirağ, Mustafa Kemal; Celik, Serkan; Kolbakir, Ferşat
Penetrating cardiac injuries have a rather high mortality and require a rapid diagnosis and emergency surgical intervention. The aim of this study was to present and discuss our experience with penetrating heart wounds. Sixteen patients with penetrating cardiac injury underwent surgical treatment at the Department of Cardiovascular Surgery between 1985-2007. The patients ranged in age from 6 to 71 years (mean age 45.1 years). The cause of cardiac injury was stab wounds in 8 patients (50%), iatrogenic reasons in 6 patients (37.5%) and shotgun wounds in 2 patients (12.5%). Exposure to the heart was accomplished by a median sternotomy in 12 patients (75%) and a left-sided anterolateral thoracotomy in 4 patients (25%). The right ventricle (RV) was injured in 7 patients (43.75%), left ventricle (LV) in 3 patients (18.75%), left atrium (LA) in 1 patient (6.25%), LV+LA in 1 patient (6.25%), and coronary arteries in 4 patients (25%). Cardiac wounds were treated by simple suture technique over Teflon or pericardial pledgets in all patients. Two patients died in the early postoperative period. The basis for successful management of penetrating cardiac trauma is effective resuscitative measures followed by early detection and definition and emergency surgical treatment of the injury.
Best, R; Mauch, F; Bauer, G
Injuries of the distal syndesmosis often accompany acute ankle sprains especially in professional team sports. While small partial syndesmosis lesions can often be missed as a consequence of impressive symptoms due to ventrolateral capsuloligamentous injuries, higher grade injuries of the syndesmosis can mostly be diagnosed without any problem. Furthermore, there is a consensus concerning the necessity of operative treatment in significantly unstable situations as well concerning conservative treatment of incomplete partial lesions. Consequently, the greatest challenge regarding diagnostic tools, quantification and optimal therapy arises in the most common form of sport-associated, complete or partial lesions of the distal syndesmosis. This review article summarizes sports-associated injuries of the distal tibiofibular syndesmosis considering the current literature and placing the emphasis on the anatomy, pathobiomechanics, diagnostics and therapy of syndesmosis lesions from an evidence-based viewpoint.
Casós, Steven R; Richardson, J David
To review the literature on the use of video-assisted thoracoscopic surgery for the diagnosis and treatment of intrathoracic injuries. Video-assisted thoracoscopic surgery is a relatively recent innovation. It was originally promoted for the treatment of retained hemothorax and the diagnosis of diaphragm injury. It is highly effective for the management of those problems. Recent studies have focused on video-assisted thoracoscopic surgery for treatment of chest wall bleeding, diagnosis of transmediastinal injuries, pericardial window and persistent pneumothorax. In properly selected patients, video-assisted thoracoscopic surgery is extremely efficacious in managing these problems. The role of video-assisted thoracoscopic surgery in the management of acute chest injury is expanding. It is an invaluable tool for the trauma surgeon.
Yang, Tuo; Sun, Yang; Zhang, Feng
Acute brain injury is a critical and emergent condition in clinical settings, which needs to be addressed urgently. Commonly acute brain injuries include traumatic brain injury, ischemic and hemorrhagic strokes. Oxidative stress is a key contributor to the subsequent injuries and impedes the reparative process after acute brain injury; therefore, facilitating an anti-oxidative approach is important in the care of those diseases. Readiness to deliver and permeability to blood brain barrier are essential for the use of this purpose. Inhaled anesthetic gases are a group of such agents. In this article, we discuss the anti-oxidative roles of anesthetic gases against acute brain injury. PMID:28217295
Glass, Hannah C; Bowman, Chelsea; Chau, Vann; Moosa, Alisha; Hersh, Adam L; Campbell, Andrew; Poskitt, Kenneth; Azakie, Anthony; Barkovich, A James; Miller, Steven P; McQuillen, Patrick S
More than 60% of newborns with severe congenital cardiac disease develop perioperative brain injuries. Known risk factors include: pre-operative hypoxemia, cardiopulmonary bypass characteristics, and post-operative hypotension. Infection is an established risk factor for white matter injury in premature newborns. In this study, we examined term infants with congenital cardiac disease requiring surgical repair to determine whether infection is associated with white matter injury. Acquired infection was specified by site - bloodstream, pneumonia, or surgical site infection - according to strict definitions. Infection was present in 23 of 127 infants. Pre- and post-operative imaging was evaluated for acquired injury by a paediatric neuroradiologist. Overall, there was no difference in newly acquired post-operative white matter injury in infants with infection (30%), compared to those without (31%). When stratified by anatomy, infants with transposition of the great arteries, and bloodstream infection had an estimated doubling of risk of white matter injury that was not significant, whereas those with single ventricle anatomy had no apparent added risk. When considering only infants without stroke, the estimated association was higher, and became significant after adjusting for duration of inotrope therapy. In this study, nosocomial infection was not associated with white matter injury. Nonetheless, when controlling for risk factors, there was an association between bloodstream infection and white matter injury in selected sub-populations. Infection prevention may have the potential to mitigate long-term neurologic impairment as a consequence of white matter injury, which underscores the importance of attention to infection control for these patients.
We present a patient with severe hypothyroidism complicated by paralytic ileus and acute kidney injury. A 65 year old male patient, diagnosed with hypothyroidism one year ago was transferred to our unit in a state of drowsiness and confusion. He was severely hypothyroid and had paralytic ileus and impaired renal function at the time of transfer. Hypokalaemia was present, and was likely to have contributed to the paralytic ileus and this together with dehydration was likely to have contributed to renal injury. Nonetheless, hypothyroidism is very likely to have been the principal precipitant of both these complications, and both paralytic ileus and acute kidney injury improved with thyroxine replacement. Unfortunately, the patient died unexpectedly eight days after admission to the unit. Hypothyroidism may induce de novo acute kidney injury or it may exacerbate ongoing chronic kidney disease. This rare complication is assumed to be due to the hypodynamic circulatory state created by thyroid hormone deficiency. Paralytic ileus is an even rarer fatal manifestation of hypothyroidism and is thought to be due to an autonomic neuropathy affecting the intestines that is reversible with thyroxine replacement. To our knowledge, both these complications have not been observed in a single patient so far. It is important that clinicians are aware of these rare manifestations of hypothyroidism as in most occasions, thyroxine deficiency may be missed, and treatment can reverse the complications. PMID:21303532
Rodrigo, Chaturaka; Gamakaranage, Champika Sssk; Epa, Dhanesha S; Gnanathasan, Ariaranee; Rajapakse, Senaka
We present a patient with severe hypothyroidism complicated by paralytic ileus and acute kidney injury. A 65 year old male patient, diagnosed with hypothyroidism one year ago was transferred to our unit in a state of drowsiness and confusion. He was severely hypothyroid and had paralytic ileus and impaired renal function at the time of transfer. Hypokalaemia was present, and was likely to have contributed to the paralytic ileus and this together with dehydration was likely to have contributed to renal injury. Nonetheless, hypothyroidism is very likely to have been the principal precipitant of both these complications, and both paralytic ileus and acute kidney injury improved with thyroxine replacement. Unfortunately, the patient died unexpectedly eight days after admission to the unit.Hypothyroidism may induce de novo acute kidney injury or it may exacerbate ongoing chronic kidney disease. This rare complication is assumed to be due to the hypodynamic circulatory state created by thyroid hormone deficiency. Paralytic ileus is an even rarer fatal manifestation of hypothyroidism and is thought to be due to an autonomic neuropathy affecting the intestines that is reversible with thyroxine replacement. To our knowledge, both these complications have not been observed in a single patient so far.It is important that clinicians are aware of these rare manifestations of hypothyroidism as in most occasions, thyroxine deficiency may be missed, and treatment can reverse the complications.
Honiden, Shyoko; Gong, Michelle N.
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
Aycock, Ryan D; Westafer, Lauren M; Boxen, Jennifer L; Majlesi, Nima; Schoenfeld, Elizabeth M; Bannuru, Raveendhara R
Computed tomography (CT) is an important imaging modality used in the diagnosis of a variety of disorders. Imaging quality may be improved if intravenous contrast is added, but there is a concern for potential renal injury. Our goal is to perform a meta-analysis to compare the risk of acute kidney injury, need for renal replacement, and total mortality after contrast-enhanced CT versus noncontrast CT. We searched MEDLINE (PubMed), the Cochrane Library, CINAHL, Web of Science, ProQuest, and Academic Search Premier for relevant articles. Included articles specifically compared rates of renal insufficiency, need for renal replacement therapy, or mortality in patients who received intravenous contrast versus those who received no contrast. The database search returned 14,691 articles, inclusive of duplicates. Twenty-six unique articles met our inclusion criteria, with an additional 2 articles found through hand searching. In total, 28 studies involving 107,335 participants were included in the final analysis, all of which were observational. Meta-analysis demonstrated that, compared with noncontrast CT, contrast-enhanced CT was not significantly associated with either acute kidney injury (odds ratio [OR] 0.94; 95% confidence interval [CI] 0.83 to 1.07), need for renal replacement therapy (OR 0.83; 95% CI 0.59 to 1.16), or all-cause mortality (OR 1.0; 95% CI 0.73 to 1.36). We found no significant differences in our principal study outcomes between patients receiving contrast-enhanced CT versus those receiving noncontrast CT. Given similar frequencies of acute kidney injury in patients receiving noncontrast CT, other patient- and illness-level factors, rather than the use of contrast material, likely contribute to the development of acute kidney injury. Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.
Alluri, Ravi; Kutscher, Hilliard L; Mullan, Barbara A; Davidson, Bruce A; Knight, Paul R
Acid pneumonitis is a major cause of sterile acute lung injury (ALI) in humans. Acid pneumonitis spans the clinical spectrum from asymptomatic to acute respiratory distress syndrome (ARDS), characterized by neutrophilic alveolitis, and injury to both alveolar epithelium and vascular endothelium. Clinically, ARDS is defined by acute onset of hypoxemia, bilateral patchy pulmonary infiltrates and non-cardiogenic pulmonary edema. Human studies have provided us with valuable information about the physiological and inflammatory changes in the lung caused by ARDS, which has led to various hypotheses about the underling mechanisms. Unfortunately, difficulties determining the etiology of ARDS, as well as a wide range of pathophysiology have resulted in a lack of critical information that could be useful in developing therapeutic strategies. Translational animal models are valuable when their pathogenesis and pathophysiology accurately reproduce a concept proven in both in vitro and clinical settings. Although large animal models (e.g., sheep) share characteristics of the anatomy of human trachea-bronchial tree, murine models provide a host of other advantages including: low cost; short reproductive cycle lending itself to greater data acquisition; a well understood immunologic system; and a well characterized genome leading to the availability of a variety of gene deletion and transgenic strains. A robust model of low pH induced ARDS requires a murine ALI that targets mainly the alveolar epithelium, secondarily the vascular endothelium, as well as the small airways leading to the alveoli. Furthermore, a reproducible injury with wide differences between different injurious and non-injurious insults is important. The murine gastric acid aspiration model presented here using hydrochloric acid employs an open tracheostomy and recreates a pathogenic scenario that reproduces the low pH pneumonitis injury in humans. Additionally, this model can be used to examine interaction of a
Parikh, Chirag R.; Moledina, Dennis G.; Coca, Steven G.; Thiessen-Philbrook, Heather R.; Garg, Amit X.
The use of novel biomarkers of acute kidney injury (AKI) in clinical trials may help evaluate treatments for AKI. Here we explore potential applications of biomarkers in simulated clinical trials of AKI using data from the TRIBE-AKI multicenter, prospective cohort study of patients undergoing cardiac surgery. First, in a hypothetical trial of an effective therapy at the time of acute tubular necrosis to prevent kidney injury progression, use of an indirect kidney injury marker such as creatinine compared to a new direct biomarker of kidney injury reduces the proportion of true acute tubular necrosis cases enrolled. The result is a lower observed relative risk reduction with the therapy, and lower statistical power to detect a therapy effect at a given sample size. Second, the addition of AKI biomarkers (interleukin-18 and NGAL) to clinical risk factors as eligibility criteria for trial enrollment in early AKI has the potential to increase the proportion of patients who will experience AKI progression and reduce trial cost. Third, we examine AKI biomarkers as outcome measures for the purposes of identifying therapies that warrant further testing in larger, multicenter, multi-country trials. In the hypothetical trial of lower cardiopulmonary bypass time to reduce the risk of postoperative AKI, the sample size required to detect a reduction in AKI is lower if new biomarkers are used to define AKI rather than serum creatinine. Thus, incorporation of new biomarkers of AKI has the potential to increase statistical power, decrease the sample size, and lower the cost of AKI trials. PMID:27165835
Ho, Simon; Feranec, Nicholas
Pneumatically powered nail guns have been used in construction since 1959. Penetrating injuries to the heart with nail guns have a wide range of presentations from asymptomatic to cardiac tamponade and exsanguination. Mortality related to cardiac nail gun injuries is similar to knife injuries, estimated at 25%. Surgical exploration is the treatment of choice. We describe a case of self-inflicted nail gun injury to the chest without hemodynamic compromise in a 51-year-old man. Computed tomography (CT) imaging confirmed nail penetrating the right ventricle, with the tip adjacent to but not violating the abdominal aorta. The patient was successfully treated with thoracotomy and foreign body removal. PMID:28191375
Acute lung injury and acute respiratory distress syndrome are clinical entities of multi-factorial origin frequently seen in traumatically injured patients requiring intensive care. We performed an unsystematic search using PubMed and the Cochrane Database of Systematic Reviews up to January 2012. The purpose of this article is to review recent evidence for the pathophysiology and the management of acute lung injury/acute respiratory distress syndrome in the critically injured patient. Lung protective ventilation remains the most beneficial therapy. Future trials should compare intervention groups to controls receiving lung protective ventilation, and focus on relevant outcome measures such as duration of mechanical ventilation, length of intensive care unit stay, and mortality. PMID:22883052
Bakowitz, Magdalena; Bruns, Brandon; McCunn, Maureen
Acute lung injury and acute respiratory distress syndrome are clinical entities of multi-factorial origin frequently seen in traumatically injured patients requiring intensive care. We performed an unsystematic search using PubMed and the Cochrane Database of Systematic Reviews up to January 2012. The purpose of this article is to review recent evidence for the pathophysiology and the management of acute lung injury/acute respiratory distress syndrome in the critically injured patient. Lung protective ventilation remains the most beneficial therapy. Future trials should compare intervention groups to controls receiving lung protective ventilation, and focus on relevant outcome measures such as duration of mechanical ventilation, length of intensive care unit stay, and mortality.
Toth, Arnold; Kovacs, Noemi; Tamas, Viktoria; Kornyei, Balint; Nagy, Mate; Horvath, Andrea; Rostas, Tamas; Bogner, Peter; Janszky, Jozsef; Doczi, Tamas; Buki, Andras; Schwarcz, Attila
Susceptibility weighted imaging (SWI) is a very sensitive tool for the detection of microbleeds in traumatic brain injury (TBI). The number and extent of such traumatic microbleeds (TMBs) have been shown to correlate with the severity of the injury and the clinical outcome. However, the acute dynamics of TMBs have not been revealed so far. Since TBI is known to constitute dynamic pathological processes, we hypothesized that TMBs are not constant in their appearance, but may progress acutely after injury. We present here five closed moderate/severe (Glasgow coma scale≤13) TBI patients who underwent SWI very early (average=23.4 h), and once again a week (average=185.8 h) after the injury. The TMBs were mapped at both time points by a conventional radiological approach and their numbers and volumes were measured with manual tracing tools by two observers. TMB counts and extents were compared between time points. TMBs were detected in four patients, three of them displaying an apparent TMB change. In these patients, TMB confluence and apparent growth were detected in the corpus callosum, coronal radiation or subcortical white matter, while unchanged TMBs were also present. These changes caused a decrease in the TMB count associated with an increase in the overall TMB volume over time. We have found a compelling evidence that diffuse axonal injury-related microbleed development is not limited strictly to the moment of injury: the TMBs might expand in the acute phase of TBI. The timing of SWI acquisition may be relevant for optimizing the prognostic utility of this imaging biomarker. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Li, Yang; Liu, Yong; Peng, XiangPing; Liu, Wei; Zhao, FeiYan; Feng, DanDan; Han, JianZhong; Huang, YanHong; Luo, SiWei; Li, Lian; Yue, Shao Jie; Cheng, QingMei; Huang, XiaoTing; Luo, ZiQiang
Background Glutamate is a major neurotransmitter in the central nervous system (CNS). Large amount of glutamate can overstimulate N-methyl-D-aspartate receptor (NMDAR), causing neuronal injury and death. Recently, NMDAR has been reported to be found in the lungs. The aim of this study is to examine the effects of memantine, a NMDAR channel blocker, on bleomycin-induced lung injury mice. Methods C57BL/6 mice were intratracheally injected with bleomycin (BLM) to induce lung injury. Mice were randomized to receive saline, memantine (Me), BLM, BLM plus Me. Lungs and BALF were harvested on day 3 or 7 for further evaluation. Results BLM caused leukocyte infiltration, pulmonary edema and increase in cytokines, and imposed significant oxidative stress (MDA as a marker) in lungs. Memantine significantly mitigated the oxidative stress, lung inflammatory response and acute lung injury caused by BLM. Moreover, activation of NMDAR enhances CD11b expression on neutrophils. Conclusions Memantine mitigates oxidative stress, lung inflammatory response and acute lung injury in BLM challenged mice. PMID:25942563
Wang, Peng; Wang, Weixing; Shi, Qiao; Zhao, Liang; Mei, Fangchao; Li, Chen; Zuo, Teng; He, Xiaobo
Acute renal injury caused by acute necrotizing pancreatitis (ANP) is a common complication that is associated with a high rate of mortality. Paeoniflorin is the active ingredient of paeonia radix and exhibits a number of pharmacological effects, such as anti‑inflammatory, anticancer, analgesic and immunomodulatory effects. The present study detected the potential treatment effects of paeoniflorin on acute renal injury induced by ANP in a rat model. The optimal dose of paeoniflorin for preventing acute renal injury induced by ANP was determined. Then, the possible protective mechanism of paeoniflorin was investigated. The serum levels of tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β and IL‑6 were measured with enzyme‑linked immunosorbent assay kits. Renal inflammation and apoptosis were measured by immunohistochemistry and terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling assay. The expression of nitric oxide in kidney tissues was also evaluated. The p38 mitogen‑activated protein kinases (MAPKs) were measured by western blotting. The results shown that paeoniflorin may ameliorate acute renal injury following ANP in rats by inhibiting inflammatory responses and renal cell apoptosis. These effects may be associated with the p38MAPK and nuclear factor‑κB signal pathway.
Zheng, Fei; Xia, Zi-An; Zeng, Yi-Fu; Luo, Jie-Kun; Sun, Peng; Cui, Han-Jin; Tang, Tao; Zhou, Yan-Tao
Traumatic brain injury (TBI) is a major cause of mortality and disability worldwide. We validated the utility of plasma metabolomics analysis in the clinical diagnosis of acute TBI in a rat model of controlled cortical impact (CCI) using gas chromatography/mass spectrometry (GC/MS). Thirty Sprague-Dawley rats were randomly divided into two groups of 15 rats each: the CCI group and sham group. Blood samples were obtained from the rats within the first 24 h after TBI injury. GC/MS measurements were performed to evaluate the profile of acute TBI-induced metabolic changes, resulting in the identification of 45 metabolites in plasma. Principal component analysis, partial least squares-discriminant analysis, orthogonal partial least square discriminant analysis using hierarchical clustering and univariate/multivariate analyses revealed clear differences in the plasma metabolome between the acute CCI group and the sham group. CCI induced distinctive changes in metabolites including linoleic acid metabolism, amino acid metabolism, galactose metabolism, and arachidonic acid metabolism. Specifically, the acute CCI group exhibited significant alterations in proline, phosphoric acid, β-hydroxybutyric acid, galactose, creatinine, L-valine, linoleic acid and arachidonic acid. A receiver operating characteristic curve analysis showed that the above 8 metabolites in plasma could be used as the potential biomarkers for the diagnosis of acute TBI. Furthermore, this study is the first time to identify the galactose as a biomarker candidate for acute TBI. This comprehensive metabolic analysis complements target screening for potential diagnostic biomarkers of acute TBI and enhances predictive value for the therapeutic intervention of acute TBI. PMID:28771528
Sade, Recep; Kantarci, Mecit; Ogul, Hayri; Bayraktutan, Ummugulsum; Uzkeser, Mustafa; Aslan, Sahin; Aksakal, Enbiya; Becit, Necip
The purpose of this study was to evaluate the efficiency and feasibility of dual-energy computed tomography (DECT) used in the diagnosis of cardiac contusion with the mildest blunt cardiac injury. This study was performed between February 2014 and September 2015; a total of 17 consecutive patients (10 men and 7 women; median age, 51 years [range: 20-78]) were enrolled in the study. The DECT was performed within 48 hours of the trauma and a subsequent follow-up DECT was performed a little less than 1 year after the first examination. All examinations were analyzed on iodine map images by 2 experienced radiologists. Interobserver and intraobserver agreement was calculated. The correlation of initial troponin level, age, and sex with number of contusion areas in the left ventricle and complete recovery of contusion were measured. The contusion areas were amorphous, with considerable variation in their size, shape, and density. Contusions were primarily located in the left free wall of the ventricle, the ventricular septum, and the apex, respectively. In 10 patients, contusion areas disappeared on follow-up examination. In 4 patients, the contusion areas decreased but were still present in the follow-up examination. The interobserver agreements were almost perfect with respect to the presence of cardiac contusion, the anatomic location of contusions, and the contusion areas (kappa values of 1.0, 1.0, and 0.9 for intraobserver agreement and 1.0, 1.0, and 1.0 for intraobserver agreement, respectively). Correlations were found between age of patients and complete recovery of contusion (P = 0.01). Dual-energy computed tomography can show cardiac contusion and could be useful and feasible for the diagnosis and follow-up of blunt cardiac injuries. Dual-energy computed tomography is a new, user-independent, and valuable imaging technique.
Deddens, Janine C.; Feyen, Dries A.; Zwetsloot, Peter-Paul; Brans, Maike A.; Siddiqi, Sailay; van Laake, Linda W.; Doevendans, Pieter A.; Sluijter, Joost P.
Background Translational failure for cardiovascular disease is a substantial problem involving both high research costs and an ongoing lack of novel treatment modalities. Despite the progress already made, cell therapy for chronic heart failure in the clinical setting is still hampered by poor translation. We used a murine model of chronic ischemia/reperfusion injury to examine the effect of minimally invasive application of cardiac progenitor cells (CPC) in cardiac remodeling and to improve clinical translation. Methods 28 days after the induction of I/R injury, mice were randomized to receive either CPC (0.5 million) or vehicle by echo-guided intra-myocardial injection. To determine retention, CPC were localized in vivo by bioluminescence imaging (BLI) two days after injection. Cardiac function was assessed by 3D echocardiography and speckle tracking analysis to quantify left ventricular geometry and regional myocardial deformation. Results BLI demonstrated successful injection of CPC (18/23), which were mainly located along the needle track in the anterior/septal wall. Although CPC treatment did not result in overall restoration of cardiac function, a relative preservation of the left ventricular end-diastolic volume was observed at 4 weeks follow-up compared to vehicle control (+5.3 ± 2.1 μl vs. +10.8 ± 1.5 μl). This difference was reflected in an increased strain rate (+16%) in CPC treated mice. Conclusions CPC transplantation can be adequately studied in chronic cardiac remodeling using this study set-up and by that provide a translatable murine model facilitating advances in research for new therapeutic approaches to ultimately improve therapy for chronic heart failure. PMID:28319168
Yu, Wen-Kuang; Ko, Hsin-Kuo; Ho, Li-Ing; Wang, Jia-Horng; Kou, Yu Ru
Respiratory neuromuscular impairment severity is known to predict weaning outcome among patients with cervical spinal cord injury; however, the impact of non-neuromuscular complications remains unexplored. This study was to evaluate possible neuromuscular and non-neuromuscular factors that may negatively impact weaning outcome. From September 2002 to October 2012, acute traumatic cervical spinal cord injury patients who had received mechanical ventilation for >48h were enrolled and divided into successful (n=54) and unsuccessful weaning groups (n=19). Various neuromuscular, non-neuromuscular factors and events during the intensive care unit stay were extracted from medical charts and electronic medical records. Variables presenting with a significant difference (p<0.2) between these two groups were included in the univariate analysis. Following univariate analysis, those significantly different variables (p<0.05) were subjected to multivariate logistic regression to identify independent predictors of unsuccessful weaning. Compared to successful weaning patients, unsuccessful weaning patients were older; more often had high level of cervical spinal cord injury (C1-3), lower pulse rates, and lower Glasgow Coma Scale score on admission, higher peak blood urea nitrogen, lower trough albumin, and lower trough blood leukocyte counts. Furthermore, unsuccessful weaning patients had a higher incidence of pneumonia, acute respiratory distress syndrome, shock and acute kidney injury during the intensive care unit stay. Multivariate logistic regression analysis revealed acute kidney injury and high level of cervical spinal cord injury were independent risk factors for failure of weaning. Importantly, patients with both risk factors showed a large increase in odds ratio for unsuccessful weaning from mechanical ventilation (p<0.001). The presence of acute kidney injury during the intensive care unit stay and high level of cervical spinal injury are two independent risk factors
Thibault-Halman, Ginette; Casha, Steven
Abstract A systematic review of the literature was performed to address pertinent clinical questions regarding deep vein thrombosis (DVT) prophylaxis in the setting of acute spinal cord injury (SCI). Deep vein thromboses are a common occurrence following SCI. Administration of low-molecular-weight heparin (LMWH) within 72 h of injury is recommended to minimize the occurrence of DVT. Furthermore, when surgical intervention is required, LMWH should be held the morning of surgery, and resumed within 24 h post-operatively. PMID:20795870
Verma, Ashish; Vanguri, Vijay K; Golla, Venkata; Rhyee, Sean; Trainor, Matthew; Abramov, Konstantin
Sodium hypochlorite is the active ingredient in bleach, a ubiquitous household disinfectant, and has known toxicities depending on route of exposure and amount. Acute kidney injury due to sodium hypochlorite exposure has never been reported. Patients that did develop nephrotoxicity following bleach exposure did so due to development of other risk factors for kidney injury such as volume depletion or sepsis. We report a patient who presented with black urine after parenteral self-administration of a large quantity of bleach. We review the clinical presentation, laboratory and biopsy findings, and outcome as well as discuss possible mechanisms of sodium hypochlorite toxicity and management strategies.
Serner, A; Weir, A; Tol, J L; Thorborg, K; Roemer, F; Guermazi, A; Yamashiro, E; Hölmich, P
Acute adductor injuries account for the majority of acute groin injuries; however, little is known about specific injury characteristics, which could be important for the understanding of etiology and management of these injuries. The study aim was to describe acute adductor injuries in athletes using magnetic resonance imaging (MRI). Male athletes with acute groin pain and an MRI confirmed acute adductor muscle injury were prospectively included. MRI was performed within 7 days of injury using a standardized protocol and a reliable assessment approach. 156 athletes presented with acute groin pain of which 71 athletes were included, median age 27 years (range 18-37). There were 46 isolated muscle injuries and 25 athletes with multiple adductor injuries. In total, 111 acute adductor muscle injuries were recorded; 62 adductor longus, 18 adductor brevis, 17 pectineus, 9 obturator externus, 4 gracilis, and 1 adductor magnus injury. Adductor longus injuries occurred at three main injury locations; proximal insertion (26%), intramuscular musculo-tendinous junction (MTJ) of the proximal tendon (26%) and the MTJ of the distal tendon (37%). Intramuscular tendon injury was seen in one case. At the proximal insertion, 12 of 16 injuries were complete avulsions. This study shows that acute adductor injuries generally occur in isolation from other muscle groups. Adductor longus is the most frequently injured muscle in isolation and in combination with other adductor muscle injuries. Three characteristic adductor longus injury locations were observed on MRI, with avulsion injuries accounting for three-quarters of injuries at the proximal insertion, and intramuscular tendon injury was uncommon. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
May, Fiona C; Stocks, Nigel; Barton, Christopher
Nicotine replacement therapy (NRT) has been shown to increase 12-month abstinence rates by as much as 50% when compared with placebo; however, NRT seems to be underutilized in the acute cardiac setting. This study explores the attitudes and beliefs of healthcare professionals regarding the use of NRT in acute cardiac inpatients, in an effort to identify and expose barriers that may impede the use of this drug in the acute cardiac care environment. Framework analysis formed the methodological foundation of the study and provided the structure for analysis of data generated via qualitative, semistructured one-on-one interviews. A purposive sample of healthcare professionals practicing in the acute cardiac care setting informed the study. Although health care professionals expressed strong views regarding the benefits of implementing NRT as a smoking cessation intervention, barriers were identified that hinder its use. Financial implications, lack of knowledge and safety issues all contributed to the institutional justification for rejecting hospital-based NRT as a secondary prevention intervention in the acute cardiac setting. To proactively reduce the incidence of secondary cardiac events, education of healthcare professionals concerning tobacco addiction and available cessation treatments in the acute cardiac patient is paramount. Nicotine replacement products require further investigation to ascertain their safety and financial viability in the acute cardiac setting. Findings may support the implementation of NRT in the inpatient cardiac setting, and ultimately help curb the incidence of smoking-related mortality owing to secondary cardiac events.
Murphy, Gavin J.; Lin, Hua; Coward, Richard J.; Toth, Tibor; Holmes, Robin; Hall, David; Angelini, Gianni D.
Objective Acute kidney injury (AKI) post-cardiac surgery is associated with mortality rates approaching 20%. The development of effective treatments is hindered by the poor homology between rodent models, the mainstay of research into AKI, and that which occurs in humans. This pilot study aims to characterise post-cardiopulmonary bypass (CPB) AKI in an animal model with potentially greater homology to cardiac surgery patients. Methods and results Adult pigs, weighing 50–75 kg, underwent 2.5 h of CPB. Pigs undergoing saphenous vein grafting procedures served as controls. Pre-CPB measures of porcine renal function were within normal ranges for adult humans. The effect of CPB on renal function; a 25% reduction in 51Cr-EDTA clearance ( p = 0.068), and a 33% reduction in creatinine clearance (p = 0.043), was similar to those reported in clinical studies. CPB resulted in tubular epithelial injury (median NAG/creatinine ratio 2.6 u mmol−1 (interquartile range (IQR): 0.81–5.43) post-CPB vs 0.48 u mmol−1 (IQR: 0.37–0.97) pre-CPB, p = 0.043) as well as glomerular and/or proximal tubular injury (median albumin/creatinine ratio 6.8 mg mmol−1 (IQR: 5.45–13.06) post-CPB vs 1.10 mg mmol−1 (IQR: 0.05–2.00) pre-CPB, p = 0.080). Tubular injury scores were significantly higher in kidneys post-CPB (median score 2.0 (IQR: 1.0–2.0) relative to vein graft controls (median score 1.0 (IQR 1.0–1.0), p = 0.019). AKI was associated with endothelial injury and activation, as demonstrated by reduced DBA (dolichos biflorus agglutinin) lectin and increased endothelin-1 and vascular cell adhesion molecule (VCAM) staining. Conclusions The porcine model of post-CPB AKI shows significant homology to AKI in cardiac surgical patients. It links functional, urinary and histological measures of kidney injury and may offer novel insights into the mechanisms underlying post-CPB AKI. PMID:19692256
Lim, Sung-Chul; Yang, Ju-Yeoul; Jang, An-Soo; Park, Yong-Uk; Kim, Young-Chul; Choi, In-Seon; Park, Kyung-Ok
Phosgene (COCl2) is a colorless oxidant gas which is heavier than air and the lethal exposure dose (LC50) in humans is 500 ppm/min. This gas was originally manufactured as an agent for chemical warfare during World War I and there had been a great deal of studies on phosgene poisoning during the early years of industrial use. It is still widely used in the synthesis of chemicals and plastics. In the modern era, however, phosgene poisoning is relatively uncommon except in accidental exposures. In Korea, there has been no report about lung injury from phosgene inhalation. We present a clinical experience with six patients accidentally exposed to phosgene. PMID:8882481
Eggers, Kai M; Lindahl, Bertil
Increased cardiac troponin concentrations in acute coronary syndrome (ACS) identify patients with ongoing cardiomyocyte necrosis who are at increased risk. However, with the use of more precise assays, cardiac troponin increases are commonly noted in other cardiovascular conditions as well. This has generated interest in the use of cardiac troponin for prognostic assessment and clinical management of these patients. In this review, we have summarized the data from studies investigating the implications of cardiac troponin concentrations in various acute and chronic conditions beyond ACS, i.e., heart failure, myocarditis, Takotsubo cardiomyopathy, aortic dissection, supraventricular arrhythmias, valve disease, pulmonary arterial hypertension, stroke, and in the perioperative setting. Cardiac troponin concentrations are often detectable and frankly increased in non-ACS conditions, in particular when measured with high-sensitivity (hs) assays. With the exception of myocarditis and Takotsubo cardiomyopathy, cardiac troponin concentrations carry strong prognostic information, mainly with respect to mortality, or incipient and/or worsening heart failure. Studies investigating the prognostic benefit associated with cardiac troponin-guided treatments however, are almost lacking and the potential role of cardiac troponin in the management of non-ACS conditions is not defined. Increased cardiac troponin indicates increased risk for adverse outcome in patients with various cardiovascular conditions beyond ACS. Routine measurement of cardiac troponin concentrations can however, not be generally recommended unless there is a suspicion of ACS. Nonetheless, any finding of an increased cardiac troponin concentration in a patient without ACS should at least prompt the search for possible underlying conditions and these should be managed meticulously according to current guidelines to improve outcome. © 2016 American Association for Clinical Chemistry.
Meisner, Allison; Kerr, Kathleen F.; Thiessen-Philbrook, Heather; Coca, Steven G.; Parikh, Chirag R.
Individual biomarkers of renal injury are only modestly predictive of acute kidney injury (AKI). Using multiple biomarkers has the potential to improve predictive capacity. In this systematic review, statistical methods of articles developing biomarker combinations to predict acute kidney injury were assessed. We identified and described three potential sources of bias (resubstitution bias, model selection bias and bias due to center differences) that may compromise the development of biomarker combinations. Fifteen studies reported developing kidney injury biomarker combinations for the prediction of AKI after cardiac surgery (8 articles), in the intensive care unit (4 articles) or other settings (3 articles). All studies were susceptible to at least one source of bias and did not account for or acknowledge the bias. Inadequate reporting often hindered our assessment of the articles. We then evaluated, when possible (7 articles), the performance of published biomarker combinations in the TRIBE-AKI cardiac surgery cohort. Predictive performance was markedly attenuated in six out of seven cases. Thus, deficiencies in analysis and reporting are avoidable and care should be taken to provide accurate estimates of risk prediction model performance. Hence, rigorous design, analysis and reporting of biomarker combination studies are essential to realizing the promise of biomarkers in clinical practice. PMID:26398494
Choi, Eunhyun; Cha, Min-Ji; Hwang, Ki-Chul
Cardiac Ca2+ cycling and signaling are closely associated with cardiac function. Changes in cellular Ca2+ homeostasis may lead to aberrant cardiac rhythm and may play a critical role in the pathogenesis of cardiac diseases, due to their exacerbation of heart failure. MicroRNAs (miRNAs) play a key role in the regulation of gene expression at the post-transcriptional level and participate in regulating diverse biological processes. The emerging evidence indicates that the expression profiles of miRNAs vary among human diseases, including cardiovascular diseases. Cardiac Ca2+-handling and signaling proteins are also regulated by miRNAs. Given the relationship between cardiac Ca2+ homeostasis and signaling and miRNA, Ca2+-related miRNAs may serve as therapeutic targets during the treatment of heart failure. In this review, we summarize the knowledge currently available regarding the role of Ca2+ in cardiac function, as well as changes in Ca2+ cycling and homeostasis and the handling of these processes by miRNAs during cardiac ischemia-reperfusion injury. PMID:25216032
Baker, Edward; Lee, Geraldine
Survival following cardiac arrest in the developed world remains below 10%. In those who survive the initial cardiac arrest, prognosis remains poor due to the onset of multi-organ failure with both significant cardiac and neurological dysfunction. Nurses have demonstrated good understanding of cardiac arrest/post arrest guidelines and have good technical skills but deficits remain in their understanding of pathophysiological processes involved in post cardiac arrest syndromes. This article aims to provide an overview of these pathophysiological processes involved in the post cardiac arrest phase, potential treatment options and the nursing interventions that may be required within the emergency department setting. This article will focus emergency nurses to become more involved in patient management at this critical phase of treatment and highlight potential early signs of deterioration. Although return of spontaneous circulation (ROSC) is crucial in the process of recovery from cardiac arrest, it is only the first of many complex stages. Given the complexity of post cardiac arrest syndrome and its impact on the patient, healthcare professionals need to understand the cellular changes associated with reperfusion injuries in order to improve outcomes. It is only through effective nursing care and medical management that improved outcomes will become more common in the future.
Lee, Sam Man; Hutchinson, Mark; Saint, David A
Cardiac ischaemic-reperfusion injury (IRI) remains the primary cause of mortality throughout the developed world. Molecular mechanisms underlying IRI are complex and are often interlinked with each other driving a synergistic response. Toll-like receptor 4 (TLR4), an immunosurveillance receptor, is known to enhance tissue injury during IRI by enhancing the inflammatory response. The release of endogenous components during IRI bind onto TLR4 leading to the activation of multiple signalling kinases. Once this event occurs these proteins are defined as danger associated molecular patterns molecules (DAMPs) or alarmins. Examples include heat shock proteins, high mobility group box one (HMGB1) and extracellular matrix proteins, all of which are involved in IRI. However, literature in the last two decades suggests that transient stimulation of TLR4 may suppress IRI and thus improve cardiac recovery. Furthermore, it remains to be seen what role TLR4 plays during ischaemic-preconditioning where acute bouts of ischaemia, preceding a harmful bout of ischaemic-reperfusion, is cardioprotective. The other question which also needs to be considered is that if transient TLR4 signalling drives a preconditioning response then what are the ligands which drive this? Hence the second part of this review explores the possible TLR4 ligands which may promote cardioprotection against IRI.
Iijima, Takehiko; Okazai, Hitoshi
It is only 20 years since TRALI was clinically recognized. As it is gradually recognized among Japanese medical community, the number of cases reported is increasing gradually. In the past nine years (1997-2005), Japanese Red Cross confirmed 118 TRALI cases and 38 possible TRALI cases in Japan. Twelve TRALI cases among them occurred during or after anesthesia on the day of operation. Since acute lung injury is caused by multiple pathological factors, it is difficult to identify its main cause as transfusion. Therefore, TRALI has been underdiagnosed and underreported. Several mechanisms have been proposed. Although anti-HLA antibody, anti-HNA antibody, or other immunoreactive substances appear to be involved in developing TRALI, underlying conditions like systemic inflammation may be required for igniting TRALI Although TRALI developed in the operating theater seems to be a small fraction of whole TRALI cases, anesthesiologists should be aware of TRALI, and remember it as one of the causes of acute lung injury.
Raman, Gaurav; Perkins, Robert M; Jaar, Bernard G
Current knowledge about managing acute kidney injury in disaster situations stems mostly from lessons learned while taking care of crush syndrome patients during major earthquakes. More recently, there has been a greater focus on emergency preparedness for ESRD management. Natural or man-made disasters create an "austere environment," wherein resources to administer standard of care are limited. Advance planning and timely coordinated intervention during disasters are paramount to administer effective therapies and save lives. This article reviews the presentation and management of disaster victims with acute kidney injury and those requiring renal replacement therapies. Major contributions of some key national and international organizations in the field of disaster nephrology are highlighted. The article intends to increase awareness about nephrology care of disaster victims, among nephrology and non-nephrology providers alike.
Gilliss, Brian M.; Looney, Mark R.
Transfusion-related acute lung injury (TRALI) is defined clinically as acute lung injury occurring within six hours of the transfusion of any blood product. It is the leading cause of transfusion-related death in the United States, but under-recognition and diagnostic uncertainty have limited clinical research to smaller case control studies. In this review we will discuss the contribution of experimental models to the understanding of TRALI pathophysiology and potential therapeutic approaches. Experimental models suggest that TRALI occurs when a host, with a primed immune system, is exposed to an activating agent such as anti-leukocyte antibody or a biologic response modifier such as lysophosphatidylcholines. Recent work has suggested a critical role for platelets in antibody-based experimental models and identified potential therapeutic strategies for TRALI. PMID:21134622
Romano, Thiago Gomes; Vieira Junior, Jose Mauro
Acute kidney injury (AKI) is a major complication in patients with acute liver failure and chronic liver disease. Hemodynamic changes appear to be the principal alterations in these conditions, therefore there should be no known structural abnormalities responsible for AKI. On the other hand, several authors have published data on structural changes known as bile cast nephropathy or cholemic nephrosis, which basically consist of the presence of bile casts in tubular lumen analogous to those observed in myeloma. Although these findings are well documented, there is a lack of reproducibility by other authors. This paper aims to discuss, through evidence-based medical literature, the role of biliary salts on kidney injury development. PMID:26251679
Kellum, John A.
Synopsis Acute kidney injury in a clinical diagnosis guided by standard criteria based on changes in serum creatinine, urine output or both. Severity of acute kidney injury is determined by the magnitude of increase in serum creatinine or decrease in urine output. Patients manifesting both oliguria and azotemia and those in which these impairments are persistent are more likely to have worse disease and worse outcomes. Both short- and long-term outcomes are worse when patients have some stage of AKI by both criteria. Duration of AKI was also a significant predictor of long-term outcomes irrespective of severity. New biomarkers for AKI may substantially aid in the risk assessment and evaluation of patients at risk for AKI. PMID:26410133
Sánchez-Quintana, Ana; Quijada-Fumero, Alejandro; Laynez-Carnicero, Ana; Breña-Atienza, Joaquín; Poncela-Mireles, Francisco J.; Llanos-Gómez, Juan M.; Cabello-Rodríguez, Ana I.; Ramos-López, María
Secondary or metastatic cardiac tumors are much more common than primary benign or malignant cardiac tumors. Any tumor can cause myocardial or pericardial metastasis, although isolated or combined tumor invasion of the pericardium is more common. Types of neoplasia with the highest rates of cardiac or pericardial involvement are melanoma, lung cancer, and breast and mediastinal carcinomas. Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Initial treatment involves chemotherapy followed by consolidation treatment to reduce the risk of relapse. In high-risk patients, the treatment of choice for consolidation is hematopoietic stem cell transplantation (HSCT). Relapse of AML is the most common cause of HSCT failure. Extramedullary relapse is rare. The organs most frequently affected, called “sanctuaries,” are the testes, ovaries, and central nervous system. We present a case with extramedullary relapse in the form of a solid cardiac mass. PMID:27642531
Shacham, Yacov; Leshem-Rubinow, Eran; Ziv-Baran, Tomer; Gal-Oz, Amir; Steinvil, Arie; Ben Assa, Eyal; Keren, Gad; Roth, Arie; Arbel, Yaron
Acute kidney injury (AKI) is associated with adverse outcomes after acute ST elevation myocardial infarction (STEMI). The recently proposed AKI network (AKIN) suggested modifications to the consensus classification system for AKI known as the risk, injury, failure, loss, end-stage (RIFLE) criteria. The aim of the current study was to compare the incidence and mortality (early and late) of AKI diagnosed by RIFLE and AKIN criteria in the STEMI patients undergoing primary percutaneous intervention (PCI). We retrospectively studied 1,033 consecutive STEMI patients undergoing primary PCI. Recruited patients were admitted between January 2008 and November 2012 to the cardiac intensive care unit with the diagnosis of acute STEMI. We compared the utilization of RIFLE and AKIN criteria for the diagnosis, classification, and prediction of mortality. The AKIN criteria allowed the identification of more patients as having AKI (9.6 vs. 3.9 %, p < 0.001) and classified more patients with stage 1 (risk in RIFLE) (7.6 vs. 1.9 %, p < 0.001) compared with the RIFLE criteria. Mortality was higher in AKI population defined by either RIFLE (46.3 vs. 6.8 %, OR 11.9, 95 % CI 6.15-23.1; p < 0.001) or AKIN (29 vs. 6.1 %; OR 6.3, 95 % CI 3.8-10.4; p < 0.001) criteria. In a multivariable logistic regression model, AKI defined with both RIFLE and AKIN was an independent predictor of both 30-day and up to 5-year all-cause mortality. However, there was no significant statistical difference in the risk provided by these two scoring systems. AKIN criteria are more sensitive in defining AKI compared with the RIFLE criteria in STEMI. However, no difference exists in the mortality risk provided by these two scoring systems.
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; Siskind, Leah J
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 aden