Clinical and procedural predictors of no-reflow in patients with acute myocardial infarction after primary percutaneous coronary intervention

BACKGROUND:

The treatment of acute myocardial infarction (AMI) is thought to restore antegrade blood flow in the infarct-related artery (IRA) and minimize ischemic damage to the myocardium as soon as possible. The present study aimed to identify possible clinical predictors for no-reflow in patients with AMI after primary percutaneous coronary intervention (PCI).

METHODS:

A total of 312 consecutive patients with AMI who had been treated from January 2008 to December 2010 at the Cardiology Department of East Hospital, Tongji University School of Medicine were enrolled in this study. Inclusion criteria were: (i) patients underwent successfully primary PCI within 12 hours after the appearance of symptoms; or (ii) patients with ischemic chest pain for more than 12 hours after a successful primary PCI within 24 hours after appearance of symptoms. Exculsion criteria were: (i) coronary artery spasm; (ii) diameter stenosis of the culprit lesion was <50% and coronary blood flow was normal; (iii) patients with severe left main coronary or multivessel disease, who had to require emergency revascularization. According to thrombolysis in myocardial infarction (TIMI), the patients were divided into a reflow group and a no-reflow group. The clinical data, angiography findings and surgical data were compared between the two groups. Univariate and multivariate logistic regressions were used to determine the predictors for no-reflow.

RESULTS:

Fifty-four (17.3%) of the patients developed NR phenomenon after primary PCI. Univariate analysis showed that age, time from onset to reperfusion, systolic blood pressure (SBP) on admission, Killip class of myocardial infarction, intra-aortic balloon pump (IABP) use before primary PCI, TIMI flow grade before primary PCI, type of occlusion, thrombus burden on baseline angiography, target lesion length, reference luminal diameter and method of reperfusion were correlated with no-reflow (P<0.05 for all). Multiple logistic regression analysis identified that age >65 years [OR=1.470, 95% confidence interval (CI) 1.460–1.490, P=0.007], long time from onset to reperfusion >6 hours (OR=1.270, 95%CI 1.160–1.400, P=0.001), low SBP on admission <100 mmHg (OR=1.910, 95%CI 1.018–3.896, P=0.004), IABP use before PCI (OR= 1.949, 95%CI 1.168–3.253, P=0.011), low (≤1) TIMI flow grade before primary PCI (OR=1.100, 95%CI 1.080–1.250, P<0.001), high thrombus burden (OR=1.600, 95%CI 1.470–2.760, P=0.030), and long target lesion (OR=1.948, 95%CI 1.908–1.990, P=0.019) on angiography were independent predictors of no-reflow.

CONCLUSION:

The occurrence of no-reflow after primary PCI for acute myocardial infarction can predict clinical, angiographic and procedural features.KEY WORDS: Acute myocardial infarction, No-reflow phenomenon, Percutaneous coronary intervention, Thrombus     

Relationship between different surgical methods,hemorrhage position,hemorrhage volume,surgical timing,and treatment outcome of hypertensive intracerebral hemorrhage

BACKGROUND:

The present study aimed to explore the relationship between surgical methods, hemorrhage position, hemorrhage volume, surgical timing and treatment outcome of hypertensive intracerebral hemorrhage (HICH).

METHODS:

A total of 1 310 patients, who had been admitted to six hospitals from January 2004 to January 2008, were divided into six groups according to different surgical methods: craniotomy through bone flap (group A), craniotomy through a small bone window (group B), stereotactic drilling drainage (group C1 and group C2), neuron-endoscopy operation (group D) and external ventricular drainage (group E) in consideration of hemorrhage position, hemorrhage volume and clinical practice. A retrospective analysis was made of surgical timing and curative effect of the surgical methods.

RESULTS:

The effectiveness rate of the methods was 74.12% for 1 310 patients after one-month follow-up. In this series, the disability rate was 44.82% 3–6 months after the operation. Among the 1 310 patients, 241 (18.40%) patients died after the operation. If hematoma volume was >80 mL and the operation was performed within 3 hours, the mortality rate of group A was significantly lower than that of groups B, C, D, and E (P<0.05). If hematoma volume was 50–80 mL and the operation was performed within 6–12 hours, the mortality rate of groups B and D was lower than that of groups A, C and E (P<0.05). If hematoma volume was 20–50 mL and the operation was performed within 6–24 hours, the mortality rate of group C was lower than that of groups A, B and D (P<0.05).

CONCLUSIONS:

Craniotomy through a bone flap is suitable for patients with a large hematoma and hernia of the brain. Stereotactic drilling drainage is suggested for patients with hematoma volume less than 80 mL. The curative effect of HICH individualized treatment would be improved via the suitable selection of operation time and surgical method according to the position and volume of hemorrhage.KEY WORDS: Hypertensive intracerebral hemorrhage, Hemorrhage position, Hemorrhage volume, Surgical timing, Stereotactic drilling drainage, Treatment effect, Individualized, Polycentric     

Impact of compliance with infection management guidelines on outcome in patients with severe sepsis: a prospective observational multi-center study

Introduction

Current sepsis guidelines recommend antimicrobial treatment (AT) within one hour after onset of sepsis-related organ dysfunction (OD) and surgical source control within 12 hours. The objective of this study was to explore the association between initial infection management according to sepsis treatment recommendations and patient outcome.

Methods

In a prospective observational multi-center cohort study in 44 German ICUs, we studied 1,011 patients with severe sepsis or septic shock regarding times to AT, source control, and adequacy of AT. Primary outcome was 28-day mortality.

Results

Median time to AT was 2.1 (IQR 0.8 – 6.0) hours and 3 hours (-0.1 – 13.7) to surgical source control. Only 370 (36.6%) patients received AT within one hour after OD in compliance with recommendation. Among 422 patients receiving surgical or interventional source control, those who received source control later than 6 hours after onset of OD had a significantly higher 28-day mortality than patients with earlier source control (42.9% versus 26.7%, P <0.001). Time to AT was significantly longer in ICU and hospital non-survivors; no linear relationship was found between time to AT and 28-day mortality. Regardless of timing, 28-day mortality rate was lower in patients with adequate than non-adequate AT (30.3% versus 40.9%, P < 0.001).

Conclusions

A delay in source control beyond 6 hours may have a major impact on patient mortality. Adequate AT is associated with improved patient outcome but compliance with guideline recommendation requires improvement. There was only indirect evidence about the impact of timing of AT on sepsis mortality.     

Efficacy of a new mutated recombinant tissue-type plasminogen activator in beagles with acute coronary artery thrombi

BACKGROUND:

Development of new coronary thrombolytic agents is hot in the market. A new drug, mutated recombinant tissue-type plasminogen activator (rtPAm), is the product of mutation of tPA by changing binding loci with plasminogen activator inhibitor (PAI)-1 to reduce the degradation. In vitro test has demonstrated that the activity of rtPAm is much higher than rtPA in the absence of PAI. The present study is to observe the efficacy of mutated recombinant tissue-type plasminogen activator (rtPAm) in coronary thrombolytic therapy.

METHODS:

A total of 30 adult beagles were equally divided into 5 groups after thrombi: vehicle group, urokinase group, rtPAm low-dose group, rtPAm medium-dose group, and rtPAm high-dose group. Thrombolytic effect and myocardial infarction were observed after thrombolytic therapy.

RESULTS:

In the urokinase group, time to reperfusion was (15.8±3.8) minutes. TIMI 2 flow was demonstrated in 4 beagles, TIMI 3 flow in 2, and re-occlusion in 4 after 90 minutes respectively. In the low-dose rtPAm group, time to reperfusion was (15±4.5) minutes; TIMI 2 flow was demonstrated in 2 beagles, TIMI 3 flow in 4, and re-occlusion in 2 after 90 minutes. In the high-dose rtPAm group, time to reperfusion was (7.5±2.6) minutes. None of the beagles showed re-occlusion after 90 minutes. The infarction areas were (2.1+0.9)% in the medium-dose rtPAm group and (0.7+0.4)% in the high-dose rtPAm group, which decreased significantly than those in the low-dose rtPAm group. The aggregation rate in the medium-dose and high-dose rtPAm groups decreased significantly than that in the urokinase group.

CONCLUSION:

rtPAm may serve as a thrombolytic agent with platelet-targeted fibrinolysis and antiplatelet aggregation activities.KEY WORDS: Urokinase, RtPA, Thrombi, D-dime, Platelet aggregation     

Active compression-decompression cardiopulmonary resuscitation (CPR) versus standard CPR for cardiac arrest patients: a meta-analysis

BACKGROUND:

Active compression-decompression cardiopulmonary resuscitation (ACDCPR) has been popular in the treatment of patients with cardiac arrest (CA). However, the effect of ACD-CPR versus conventional standard CPR (S-CRP) is contriversial. This study was to analyze the efficacy and safety of ACD-CPR versus S-CRP in treating CA patients.

METHODS:

Randomized or quasi-randomized controlled trials published from January 1990 to March 2011 were searched with the phrase “active compression-decompression cardiopulmonary resuscitation and cardiac arrest” in PubMed, EmBASE, and China Biomedical Document Databases. The Cochrane Library was searched for papers of meta-analysis. Restoration of spontaneous circulation (ROSC) rate, survival rate to hospital admission, survival rate at 24 hours, and survival rate to hospital discharge were considered primary outcomes, and complications after CPR were viewed as secondary outcomes. Included studies were critically appraised and estimates of effects were calculated according to the model of fixed or random effects. Inconsistency across the studies was evaluated using the I2 statistic method. Sensitivity analysis was made to determine statistical heterogeneity.

RESULTS:

Thirteen studies met the criteria for this meta-analysis. The studies included 396 adult CA patients treated by ACD-CPR and 391 patients by S-CRP. Totally 234 CA patients were found out hospitals, while the other 333 CA patients were in hospitals. Two studies were evaluated with high-quality methodology and the rest 11 studies were of poor quality. ROSC rate, survival rate at 24 hours and survival rate to hospital discharge with favorable neurological function indicated that ACD-CPR is superior to S-CRP, with relative risk (RR) values of 1.39 (95% CI 0.99–1.97), 1.94 (95% CI 1.45–2.59) and 2.80 (95% CI 1.60–5.24). No significant differences were found in survival rate to hospital admission and survival rate to hospital discharge for ACD-CPR versus S-CRP with RR values of 1.06 (95% CI 0.76–1.60) and 1.00 (95% CI 0.73–1.38).

CONCLUSION:

Quality controlled studies confirmed the superiority of ACD-CPR to S-CRP in terms of ROSC rate and survival rate at 24 hours. Compared with S-CRP, ACD-CPR could not improve survival rate to hospital admission or survival rate to hospital discharge.KEY WORDS: Active compression-decompression, Cardiopulmonary resuscitation, Cardiac arrest, Meta-analysis     

Mild hypothermia in improving multiple organ dysfunction after cardiac arrest

BACKGROUND:

Resuscitation after cardiac arrest (CA) with a whole-body ischemia–reperfusion injury causes brain injury and multiple organ dysfunction (MODS). This study aimed to determine whether mild systemic hypothermia could decrease multiple organ dysfunctions after resuscitation from cardiac arrest.

METHODS:

The patients who had been resuscitated after cardiac arrest were reviewed. During the resuscitation they had been assigned to undergo therapeutic hypothermia (target temperature, 32°C to 34°C, measured in the rectum) over a period of 24 to 36 hours or to receive standard treatment with normothermia. Markers of different organ injury were evaluated for the first 72 hours after recovery of spontaneous circulation (ROSC).

RESULTS:

At 72 hours after ROSC, 23 patients in the hypothermia group for whom data were available had favorable neurologic, myocardial, hepatic and pulmonic outcomes as compared with 26 patients in the normothermia group. The values of renal function were not significantly different between the two groups. However, blood coagulation function was badly injured in the hypothermia group.

CONCLUSION:

In the patients who have been successfully resuscitated after cardiac arrest, therapeutic mild hypothermia can alleviate dysfunction after resuscitation from cardiac arrest.KEY WORDS: Cardiac arrest, Ischemia reperfusion injury, Mild hypothermia, Multiple organ dysfunction     

Can venous blood gas analysis be used for predicting seizure recurrence in emergency department?

BACKGROUND:

Epileptic seizures account for 1%–2% of all admissions of patients to the emergency department (ED). The present study aimed to determine whether venous blood pH, bicarbonate, base excess, and lactate levels taken within 1 hour of the last seizure episode help to determine seizure recurrence in emergency departments.

METHODS:

A cross-sectional study was conducted in the emergency department (ED) between January and July, 2012. Patients who were admitted to the emergency department consecutively were included in the study if they were 14 years or older and within 1 hour after last seizure. Demographics, seizure type, use of antiepileptic drugs, observation period at the emergency department, seizure recurrence, pH, bicarbonate, base excess, and lactate levels from venous blood gas analysis were determined.

RESULTS:

A total of 94 patients aged 14 years or older were included in the study. Of these patients, 10.6% (n=10) experienced recurrent seizures in the observation period at the emergency department. To predict recurrent seizures in ED, threshold venous blood gas values were determined as follows: pH<7.245 [sensitivity 80% (95%CI: 44–96), negative predictive value 96.9% (95%CI: 88.3–99.4)], bicarbonate<17.1 mmol/L [sensitivity 80% (95%CI: 44–96), negative predictive value 97% (95%CI: 89–99.5)], base excess<–11.1 mEq/L [sensitivity 80% (95%CI: 44–96), negative predictive value 97% (95%CI: 89–99)], and lactate>7.65 mmol/L [sensitivity 80% (95%CI: 44–96), negative predictive value 96.6% (95%CI: 87–99)].

CONCLUSION:

If venous blood gas analysis is made on pH, base excess, lactate and bicarbonate immediately one hour after the last epileptic seizure episode, it is possible to predict whether the patient will have seizure recurrence.KEY WORDS: Seizure recurrence, Venous blood gas, Emergency department     

Effects of Hemin on neuroglobin expression after cardiopulmonary resuscitation in rats

BACKGROUND:

Despite a large amount of resuscitation research, the survival rate after cardiac arrest remains low, and brain injury is the key issue. Neuroglobin (NGB) is an oxygen-binding heme protein found in the brain with a protection role against ischemic-hypoxic brain injury. Hemin is an effective activator of neuroglobin. This study was undertaken to assess the effect of hemin on expression of neuroglobin (NGB) in the cerebral cortex, neuro-deficit score (NDS) and pathological changes after cardiopulmonary resuscitation (CPR) in rats.

METHODS:

A total of 120 male Sprague-Dawley (SD) rats were randomly divided into a control group (A), a CPR group (B) and a Hemin group (C). The animal model of cardiac arrest (CA) induced by asphyxia and CPR was established. NGB expression in the cerebral cortex with immunohistochemistry, NDS and pathological changes in the cerebral cortex were examined at 3, 6, 12, 24 hours after recovery of spontaneous circulation (ROSC) in each group. Experimental data were treated as one-factor analysis of variance and the Tukey test.

RESULTS:

In comparison with group A, NGB expression was increased significantly at 12 and 24 hours after ROSC (P<0.05 or P<0.01), NDS was decreased significantly at each time point after ROSC (P<0.01), and pathological changes were severe at each time point after ROSC in group B. In comparison with group A, NGB expression was increased significantly at 6, 12, 24 hours after ROSC (P<0.05 or P<0.01), NDS was decreased significantly at 3, 6, 12 hours after ROSC (P<0.01) in group C. In comparison with group B, NGB expression was increased significantly at 12 and 24 hours after ROSC, NDS was increased significantly at 12 and 24 hours after ROSC, and pathological changes were milder in group C.

CONCLUSION:

There were increased NGB expression in the cerebral cortex, decreased NDS, and severe pathological changes after CPR in rats. Hemin treatment up-regulated expression of NGB, improved NDS, mitigated pathological changes, and alleviated cerebral injury after CPR.KEY WORDS: Cardiopulmonary resuscitation, Neuroglobin, Neurodeficit score, Hemin, Cerebral injury, Rats     

International normalized ratio as a predictor of mortality in trauma patients in India

BACKGROUND:

Hemorrhage is the second leading cause of death in trauma patients preceded only by traumatic brain injury. But hemorrhagic shock is the most common cause of preventable death within 6 hours of admission. Traumatic coagulopathy is a hypocoagulable state that occurs in the most severely injured. International normalized ratio (INR) and its relationship with trauma mortality have not been studied specifically. This study aimed to establish a predictive value of INR for trauma-related mortality.

METHODS:

A total of 99 trauma patients aged 18–70 years were included in the study. Their INR was determined and patient progression was followed up till death/discharge. According to previous retrospective studies, the cutoff value for INR in our study was kept at 1.5.

RESULTS:

The total mortality rate of the patients was 16.16% (16/99). The mean INR was 1.45 with a SD of 1.35. INR was deranged in a total of 14 patients (14.14%). Of these patients, 11 died (78.57%) and 3 survived. INR was deranged in 11 (68.75%) of the 16 patients who died, but 5 deaths (31.25%) had normal INR values. The sensitivity of INR was 69% (95%CI 41%–88%) and the specificity 96% (95%CI 90%–99%). The diagnostic accuracy of INR was 92% (95%CI 85%–96%). Positive predictive value and negative predictive value were 79% (95%CI 49%–95%) and 94% (95%CI 87%–98%), respectively.

CONCLUSION:

Our results showed that INR is a good predictor of mortality in trauma patients.KEY WORDS: Hemorrhage, Trauma, International normalized ratio, Mortality     

The relationship between serum levels of uric acid and prognosis of infection in critically ill patients

BACKGROUND:

Serum uric acid level is associated with some chronic diseases and prognosis of severe infection. This study aimed to investigate the relationship between serum uric acid (SUA) and prognosis of infection in critically ill patients.

METHODS:

The data from 471 patients with infection admitted from January 2003 to April 2010 were analyzed retrospectively at Huashan Hospital Affiliated to Fudan University, Shanghai, China. The data of SUA, serum creatinine, blood urea nitrogen (BUN) and other relevant examinations within 24 hours after admission were recorded and the levels of SUA in those patients were described, then Student’s t test was used to evaluate the relationship between SUA and pre-existing disorders. Different levels of SUA were graded for further analysis. The Chi-square test was used to examine the difference in the prognosis of infection.

RESULTS:

The mean initial level of SUA within 24 hours after admission was 0.232±0.131 mmol/L and the median was 0.199 mmol/L. Remarkable variations in the initial levels of SUA were observed in patients with pre-existing hypertension (t=–3.084, P=0.002), diabetes mellitus (t=–2.487, P=0.013), cerebral infarction (t=–3.061, P=0.002), renal insufficiency (t=–4.547, P<0.001), central nervous system infection (t=5.096, P<0.001) and trauma (t=2.875, P=0.004). SUA was linearly correlated with serum creatinine and BUN (F=159.470 and 165.059, respectively, P<0.001). No statistical correlation was found between the initial levels of SUA and prognosis of infection (χ2=60.892, P=0.100).

CONCLUSION:

The current study found no direct correlation between the initial levels of SUA after admission and prognosis of infection in critically ill patients.KEY WORDS: Intensive care unit, Infection, Uric acid, Blood urea nitrogen, Creatinine, Pneumonia, Central nervous system infection, Renal insufficiency, Prognosis     

Effect of β-sodium aescinate on hypoxia-inducible factor-1α expression in rat brain cortex after cardiopulmonary resuscitation

BACKGROUND:

This study was undertaken to investigate the expression of hypoxia-inducible factor-1α (HIF-1α) in rat cerebral cortex and the effects of β-sodium aescinate (SA) administration after return of spontaneous circulation (ROSC).

METHODS:

Sixty rats were divided into three groups: SA group, injected intraperitoneally with SA instantly after ROSC; control group, injected intraperitoneally with normal saline; and sham-operated group, without cardiac arrest or SA. The cardiac arrest model was established using asphyxiation and intravenous potassium chloride. Blood was sampled 1, 6, 12, and 24 hours after ROSC. Protein and mRNA levels of HIF-1α, VEGF and EPO were detected in the cerebral cortex by immunohistochemistry and real-time RT-PCR; serum levels of NSE and S100β were determined by enzyme-linked immunosorbent assays.

RESULTS:

Serum S100β and NSE were significantly increased in the control group versus the sham-operated group 1, 6, 12 and 24 hours after ROSC (P<0.05). Protein and mRNA levels of HIF-1α, VEGF and EPO were significantly increased in the control rats (P<0.05). Serum NSE and S100β were significantly decreased in the SA group versus the control group 1, 6, 12 and 24 hours after ROSC (P<0.05). Protein and mRNA levels of HIF-1α, VEGF and EPO were significantly increased in the SA group (P<0.05).

CONCLUSIONS:

The expression of HIF-1α is increased in rat cerebral cortex after ROSC, and SA up-regulates the expression of HIF-1α. The up-regulation of HIF-1α improves the resistance of the cortex to ischemia and hypoxia and contributes to neuroprotection, possibly because of up-regulation of EPO and VEGF expression.KEY WORDS: Cardiopulmonary resuscitation, HIF-1α, Erythropoietin, Vascular endothelial growth factor, β-sodium aescinate, Neuroprotection     

Effect of tumor necrosis factor-α on ventricular arrhythmias in rats with acute myocardial infarction in vivo

BACKGROUND:

Acute myocardial infarction (AMI) is an acute cardiovascular emergency. This study was undertaken to assess the effect of tumor necrosis factor-α (TNF-α) on ventricular arrhythmias induced by AMI in rats in vivo.

METHODS:

Two hundred and forty male Wistar rats were randomized into a sham-operation group, an AMI group, and a recombinant human tumor necrosis factor receptor:Fc fusion protein(rhTNFR:Fc) group. Acute anterior wall myocardial infarction was produced in the AMI group by ligating the left anterior descending coronary artery (LAD), and there was no ligation but operation in the sham-operation group. The rhTNFR:Fc group was treated with rhTNFR:Fc(10 mg/kg), a TNF-α antagonist, 24 hours before LAD ligation. The spontaneous and induced programmed electrical stimulation ventricular arrhythmias were recorded at baseline and 10 minutes, 20 minutes, 30 minutes, 60 minutes, 3 hours, 6 hours and 12 hours after ligation. At the same time the protein and mRNA expression levels of TNF-α among different groups were detected by histochemistry and real-time fluorescent quantitative PCR.

RESULTS:

Expression of TNF-α increased markedly from 10 minutes after infarction, peaked at 20-30 minutes, and returned to baseline gradually in the AMI group and rhTNFR:Fc group. The time-windows of spontaneous and induced ventricular arrhythmias were similar. Compared with the AMI group, the rhTNFR:Fc group showed a lesser expression of TNF-α protein and a lower incidence of ventricular arrhythmias (P<0.05). There was no obvious change in the sham-operation group.

CONCLUSION:

The expression of TNF-α induced by AMI could contribute to the onset of ventricular arrhythmias.KEY WORDS: Acute myocardial infarction, Tumor necrosis factor-α, Ventricular arrhythmia, Recombinant human tumor necrosis factor receptor, Fc fusion protein (rhTNFR: Fc)     

The status of temporomandibular and cervical spine education in credentialed orthopedic manual physical therapy fellowship programs: a comparison of didactic and clinical education exposure

Objective:

The purpose of this investigation was to establish a baseline of physical therapist education on temporomandibular disorders (TMD)-related topics during credentialed orthopedic manual physical therapy fellowship training and compare it to cervical spine disorders education.

Method:

An online survey was distributed electronically to each fellowship program credentialed by the American Physical Therapy Association (APTA) and recognized by the Academy of Orthopedic Manual Physical Therapists (AAOMPT). Data were analyzed to compare overall exposure to TMD educational content, including a direct comparison of TMD and cervical spine disorders education.

Results:

The response rate was 79%. Thirteen programs (87%) reported providing both didactic and clinical training on both TMD and cervical spine disorders. Didactic education for cervical spine disorders ranged from 16–20 hours to over 25 hours, whereas TMD hours ranged from 0 to 6–10 hours. Clinical education for cervical spine disorders ranged from 11–15 hours to over 25 hours, whereas TMD hours ranged from 0 to 6–10 hours. The number of hours of exposure during didactic training and the number of patients exposed to during clinical training were significantly different when comparing TMD to cervical spine disorders exposure (P<0.0001).

Discussion:

The data indicate a lack of uniformity between credentialed fellowship programs in orthopedic manual physical therapy with respect to the extent to which programs expose trainees to evaluation and management of TMD. There is consistency in that all programs provided more training on cervical spine disorders than TMD. Despite a high level of clinical specialization, fellows-in-training receive minimal TMD education.     

Repair of damaged intestinal mucosa in a mouse model of sepsis

BACKGROUND:

The intestine is not only the main target attacked by sepsis but also the vital organ which mediated sepsis. The recovery of the damaged intestinal barrier structure and function is related to the occurrence and outcome of multiple organ dysfunction syndrome (MODS). How to protect and reduce the damage of the intestinal mucosa and how to promote the reconstruction of the intestinal mucosa have been the important topics in sepsis for many years. This study aimed to investigate the influential factors of intestinal mucosal reconstruction after intestinal epithelial injury in vivo in a mouse model of sepsis.

METHODS:

Mice were subjected to cecal ligation and puncture (CLP) for induction of sepsis to assess intestinal mucosal damage, epithelial cell apoptosis, and transformed number of goblet cells, and to detect the concentration of TNF-α, IL-1 and TGF-β1 and TFF3 (trefoil factor 3) expression in the small intestinal mucosa. All above were performed by HE staining, western blot, ELISA and immunohistochemistry respectively. The experimental animals were divided into a sepsis group and a sham-operation group. The animals with sepsis were separately killed at 6 (7 animals), 24 (7 animals) and 48 hours (7 animals) after CLP.

RESULTS:

Injured intestinal mucosa was observed in the 3 groups under a light microscope, in which damage scores in the 24-hour and 48-hour groups were higher than in the 6-hour group and no difference was found between the two groups. Moreover, less of goblet cells or other epithelial cells adjacent to the injured surface migrated into the wound to cover the denuded area. The number of goblet cells was substantially decreased in the three CLP groups compared with the sham-operation group. Protein levels of IL-1 and TNF-α were significantly increased by 3–4 fold at all time points when compared with the sham-operation group, and cleaved caspase-3 by 4 fold. Although TFF3 expression was modestly increased for 6 hours after the onset of CLP, it appeared to decline at 24 hours and 48 hours as shown by Western blot. A similar tendency was observed upon TGF-β1, i.e. the protein level was not elevated at 24 hours and 48 hours, but increased modestly at 6 hours.

CONCLUSIONS:

Sepsis from CLP shows less restitution on the surface of injured intestinal mucosa. There is evidence that both constant inflammatory reaction and epithelial cell apoptosis may affect mucosal reestablishment of the intestine at the onset of sepsis. Mucosa after severe sepsis showed the state of high inflammation, and declined goblet cell function and mucosal reconstruction, which affected the repair of damaged intestinal barrier. Constant inflammatory reaction, and declined goblet cell function and mucosal reconstruction ability may affect the reestablishment of intestinal mucosa at the onset of sepsis.KEY WORDS: Sepsis, Cecal ligation and puncture, Intestinal mucosa, Restitution, Goblet cells, Intestinal trefoil factor 3, Transforming growth factor β1, Cysteine-containing aspartate-specific proteases     

Cardioprotective effect of erythropoietin on sepsis-induced myocardial injury in rats

BACKGROUND:

Sepsis-induced myocardial injury is one of the major predictors of morbidity and mortality of sepsis. The cytoprotective function of erythropoietin (EPO) has been discovered and extensively studied. However, the cardioprotective effects of EPO on sepsis-induced myocardial injury in the rat sepsis model has not been reported.

METHODS:

The rat models of sepsis were produced by cecal ligation and perforation (CLP) surgery. Rats were randomly (random number) assigned to one of three groups (n=8 for each group): sham group, CLP group and EPO group (1000 IU/kg erythropoietin). Arterial blood was withdrawn at 3, 6, 12, and 24 hours after CLP. cTnI, BNP, CK-MB, LDH, AST, TNF-α, IL-6, IL-10, and CRP were tested by the ELISA assay. Changes of hemodynamic parameters were recorded at 3, 6, 12, 24 hours after the surgery. Histological diagnosis was made by hematoxylin and eosin. Flow cytometry was performed to examine cell apoptosis, myocardium mitochondrial inner membrane potential, and NF-κB (p65). Survival rate at 7 days after CLP was recorded.

RESULTS:

In the CLP group, myocardial enzyme index and inflammatory index increased at 3, 6, 12 and 24 hours after CLP compared with the sham group, and EPO significantly blocked the increase. Compared with the CLP group, EPO significantly improved LVSP, LV +dp/dt_max, LV −dp/dt_min, and decreased LVEDP at different time. EPO blocked the reduction of mitochondrial transmembrane potential, suppressed the cardiomyocyte apoptosis, inhibited the activation of NF-κB, and reduced the production of proinflmmatory cytokines. No difference in the survival rate at 7 days was observed between the CLP group and the EPO group.

CONCLUSION:

Exogenous EPO has cardioprotective effects on sepsis-induced myocardial injury.KEY WORDS: Sepsis, Sepsis-induced myocardial injury, Apoptosis, Chondriosome membrane potential, Nuclear factor κB p65, Erythropoietin, Inflammatory cytokines, Rat     

Two acute kidney injury risk scores for critically ill cancer patients undergoing non-cardiac surgery

BACKGROUND:

Several risk scoures have been used in predicting acute kidney injury (AKI) of patients undergoing general or specific operations such as cardiac surgery. This study aimed to evaluate the use of two AKI risk scores in patients who underwent non-cardiac surgery but required intensive care.

METHODS:

The clinical data of patients who had been admitted to ICU during the first 24 hours of ICU stay between September 2009 and August 2010 at the Cancer Institute, Chinese Academy of Medical Sciences & Peking Union Medical College were retrospectively collected and analyzed. AKI was diagnosed based on the acute kidney injury network (AKIN) criteria. Two AKI risk scores were calculated: Kheterpal and Abelha factors.

RESULTS:

The incidence of AKI was 10.3%. Patients who developed AKI had a increased ICU mortality of 10.9% vs. 1.0% and an in-hospital mortality of 13.0 vs. 1.5%, compared with those without AKI. There was a significant difference between the classification of Kheterpal’s AKI risk scores and the occurrence of AKI (P<0.001). There was no significant difference between the number of Abelha’s AKI risk scores and the occurrence of AKI (P=0.499). Receiver operating characteristic curves demonstrated an area under the curve of 0.655±0.043 (P=0.001, 95% confidence interval: 0.571–0.739) for Kheterpal’s AKI risk score and 0.507±0.044 (P=0.879, 95% confidence interval: 0.422–0.592) for Abelha’s AKI risk score.

CONCLUSION:

Kheterpal’s AKI risk scores are more accurate than Abelha’s AKI risk scores in predicting the occurrence of AKI in patients undergoing non-cardiac surgery with moderate predictive capability.KEY WORDS: Risk factor, Acute kidney injury, Surgery     

Association of ALOX5, LTA4H and LTC4S gene polymorphisms with ischemic stroke risk in a cohort of Chinese in east China

BACKGROUND:

Genetic variations of the 5-lipoxygenase activating protein and leukotriene A4 hydrolase genes that confer an increased risk of ischemic stroke have implicated the family of leukotrienes as potential mediators of ischemic stroke. This study aimed to explore the association of ALOX5, LTA4H and LTC4S gene polymorphisms with ischemic stroke risk in a cohort of Chinese in east China.

METHODS:

This case-control study consisted of 690 patients with ischemic stroke and 690 controls. Polymorphisms of ALOX5 rs2029253 A/G, LTA4H rs6538697 T/C, and LTC4S rs730012 A/C were genotyped by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. The multivariate logistic regression model was used to exclude the effects of conventional risk factors on ischemic stroke.

RESULTS:

Carriers of C allele in rs730012 were more susceptible to ischemic stroke (OR: 1.37; 95%CI: 1.08–1.73; P=0.009). The rs2029253 GG genotype showed a risk-reducing effect on ischemic stroke (OR: 0.72; 95%CI: 0.55–0.93; P=0.013) while the rs6538697 CC genotype had an increased risk of ischemic stroke (OR: 1.77; 95%CI: 1.09–2.89; P=0.022). The rs730012 variant was not associated with ischemic stroke risk after adjusting confounding factors (P>0.05).

CONCLUSION:

The present study suggested that gene polymorphisms in the leukotrienes pathway may exert influences, with independent genetic effects, on ischemic stroke susceptibility in a cohort of Chinese in east China.KEY WORDS: Leukotrienes, Gene polymorphisms, Risk factors, Ischemic stroke     

Language affects length of stay in emergency departments in Queensland public hospitals

BACKGROUND:

A long length of stay (LOS) in the emergency department (ED) associated with overcrowding has been found to adversely affect the quality of ED care. The objective of this study is to determine whether patients who speak a language other than English at home have a longer LOS in EDs compared to those whose speak only English at home.

METHODS:

A secondary data analysis of a Queensland state-wide hospital EDs dataset (Emergency Department Information System) was conducted for the period, 1 January 2008 to 31 December 2010.

RESULTS:

The interpreter requirement was the highest among Vietnamese speakers (23.1%) followed by Chinese (19.8%) and Arabic speakers (18.7%). There were significant differences in the distributions of the departure statuses among the language groups (Chi-squared=3236.88, P<0.001). Compared with English speakers, the Beta coefficient for the LOS in the EDs measured in minutes was among Vietnamese, 26.3 (95%CI: 22.1–30.5); Arabic, 10.3 (95%CI: 7.3–13.2); Spanish, 9.4 (95%CI: 7.1–11.7); Chinese, 8.6 (95%CI: 2.6–14.6); Hindi, 4.0 (95%CI: 2.2–5.7); Italian, 3.5 (95%CI: 1.6–5.4); and German, 2.7 (95%CI: 1.0–4.4). The final regression model explained 17% of the variability in LOS.

CONCLUSION:

There is a close relationship between the language spoken at home and the LOS at EDs, indicating that language could be an important predictor of prolonged LOS in EDs and improving language services might reduce LOS and ease overcrowding in EDs in Queensland’s public hospitals.KEY WORDS: Emergency department, Language, Length of stay     

Glucocorticoid receptor expression on acute lung injury induced by endotoxin in rats

BACKGROUND:

In cases of severe sepsis and septic shock, a series of pathophysiological changes lead to multiple organ dysfunction syndrome. This study aimed to investigate the expression of glucocorticoid receptor mRNA in the rat lung following endotoxin (LPS) induced shock.

METHODS:

Totally 56 SD rats were randomly divided into 4 groups: LPS shock group (n=16), LPS+vasoactive intestinal peptide group(VIP) group, (n=16), LPS+VIP+ glucocorticoid (GC) group, (n=16),and control group (n=8). LPS shock was induced by intravenous injection of LPS (10 mg/kg) in rats. Within 15 minutes after LPS injection, rats in the treatment groups received VIP (5 nmol/kg) or VIP and methylprednisolone (3 mg/kg). The control group was given normal saline instead of LPS. The rats of the four groups were sacrificed at 6 hours,24 hours after injection respectively, and the lung tissues were collected. Pathological changes of the lungs were examined by light microscopy and electron microscopy. GRmRNA expression in the lung tissues was evaluated by RT-PCR.

RESULTS:

In the LPS shock group, lung histopathology demonstrated destruction of the alveolar space,widening of the inter-alveolar space, inflammatory cell infiltration and interstitial edema. However,pathological changes in the LPS+ VIP group and LPS+ VIP+GC group were milder than those in the LPS shock group. Six hours after LPS injection, GR mRNA expression was down-regulated in the LPS group (0.72± 0.24) and LPS+ VIP group (0.88±0.27) (P<0.05) as compared with the control group (1.17±0.22). The LPS shock group showed a more significant down-regualtion than the LPS+VIP group, but the difference was not statistically significant (P>0.05). In contrast, GRmRNA expression in the LPS+ VIP+GC group was significantly up-regulated at 6 hours and further at 24 hours (1.45±0.32 and 1.91±0.46 respectively) (P<0.05).

CONCLUSION:

GrmRNA expression decreased in LPS induced lung injury in rats. Combined treatment with VIP and GC mitigated lung injury ang inflammation. The mechanism may be related to up-regulation of GR mRNA expression.KEY WORDS: Glucocorticoid, GRmRNA, Vasoactive intestinal peptide, LPS, Shock, Inflammation, Lung injury, Rat     

PKCα signaling pathway involves in TNF-α-induced IP3R1 expression in human mesangial cells

BACKGROUND:

This study aimed to explore the effects of TNF-α on the expression of IP₃R1 mRNA and protein in human mesangial cells (HMCs), and to elucidate the mechanism of TNF-α relating to IP₃R1 expression in the occurrence of hepatorenal syndrome (HRS).

METHODS:

HMCs were stimulated by tumor (TNF-α) with 100 ng/mL for different hours (2, 4, 8, and 24 hours). The expression changes of IP₃R1 mRNA and protein were detected by quantitative real-time polymerase chain reaction and immunoblotting. Several inhibitors including D609, {"type":"entrez-nucleotide","attrs":{"text":"U73122","term_id":"4098075","term_text":"U73122"}}U73122, PP1, safingol, rottlerin and non-radioactive protein kinase C (PKC) were used to examine the mechanism of signal transduction of TNF-α-regulated IP₃R1 in HMCs.

RESULTS:

The levels of IP₃R1 mRNA at 2 hours after TNF-α exposure were significantly enhanced and peaked at 8 hours in HMCs (P<0.01), then descended at 24 hours (P<0.01). The levels of IP₃R1 protein at 4 hours after TNF-α exposure were obviously increased and peaked at 24 hours after TNF-α exposure (P<0.01). Compared to the control group, safingol (PKCα inhibitor) and D609 (phosphatidylcholine-specific phospholipase C inhibitor) significantly blocked the TNF-αinduced expression of IP₃R1 mRNA (3.30±0.81 vs. 1.95±0.13, P<0.05; 2.10±0.49, P<0.01) and IP₃R1 protein (3.09±0.13 vs. 1.86+0.39, P<0.01; 1.98±0.02, P<0.01). TNF-α promoted PKCα activation with maximal PKCα phosphorylation that occurred 8 hours after stimulation measured by non-radioactive PKC assay, and the effect was markedly attenuated by pretreatment with D609 or safingol.

CONCLUSION:

TNF-α increased the expression of IP₃R1 and this was mediated, at least in part, through the PC-PLC/PKCα signaling pathways in HMCs.KEY WORDS: TNF-α, Hepatorenal syndrome, Human mesangial cells, Protein kinase C, Phosphatidylcholine-specific phospholipase C