The accurate measurement of arterial wave properties in terms of arterial wave transit time (τw) and wave reflection factor (Rf) requires simultaneous records of aortic pressure and flow signals. However, in clinical practice, it will be helpful to describe the pulsatile ventricular afterload using less-invasive parameters if possible. We investigated the possibility of systolic aortic pressure-time area (PTAs), calculated from the measured aortic pressure alone, acting as systolic workload imposed on the rat diabetic heart. Arterial wave reflections were derived using the impulse response function of the filtered aortic input impedance spectra. The cardiovascular condition in the rats with either type 1 or type 2 diabetes was characterized by (1) an elevation in PTAs; and (2) an increase in Rf and decrease in τw. We found that an inverse linear correlation between PTAs and arterial τw reached significance (τw = 38.5462 − 0.0022 × PTAs; r = 0.7708, P < 0.0001). By contrast, as the PTAs increased, the reflection intensity increased: Rf = –0.5439 + 0.0002 × PTAs; r = 0.8701; P <0 .0001. All these findings suggested that as diabetes stiffened aortas, the augmented aortic PTAs might act as a useful index describing the diabetes-related deterioration in systolic ventricular workload.
The biological outcome of TMPRSS2:ERG chromosomal translocations in prostate cancer (PC) remains poorly understood. To address this, we compared the transcriptional effects of TMPRSS2:ERG expression in a transgenic mouse model with those of ERG knockdown in a TMPRSS2:ERG-positive PC cell line. This reveals that ERG represses the expression of a previously unreported set of androgen receptor (AR)-independent neuronal genes that are indicative of neuroendocrine (NE) cell differentiation-in addition to previously reported AR-regulated luminal genes. Cell sorting and proliferation assays performed after sustained ERG knockdown indicate that ERG drives proliferation and blocks the differentiation of prostate cells to both NE and luminal cell types. Inhibition of ERG expression in TMPRSS2:ERG-positive PC cells through blockade of AR signaling is tracked with increased NE gene expression. We also provide evidence that these NE cells are resistant to pharmacological AR inhibition and can revert to the phenotype of parental cells upon restoration of AR/ERG signaling. Our findings highlight an ERG-regulated mechanism capable of repopulating the parent tumor through the transient generation of an anti-androgen therapy-resistant cell population, suggesting that ERG may have a direct role in preventing resistance to anti-androgen therapy.
Background/Purpose: Despite general recommendation of short-course antibiotic prophylaxis, prolonged antibiotic use is still commonly reported in clinical settings. This study compared the efficacy of 1-day versus 3-day antibiotic prophylaxis in preventing surgical site infection (SSI) in patients undergoing coronary artery bypass graft (CABG).Methods: This prospective, randomized control study was performed in a tertiary-care medical center from June 2002 to April 2004. Patients underwent non-emergency CABG and were randomized into two groups receiving either 1 day or 3 days cefazolin prophylaxis. The SSI rates were compared between the two groups.Results: During the study period, 231 patients were enrolled, 120 in the 1-day group and 111 in the 3-day group. Twenty-two episodes of SSI were observed within 1 month after operation: 13 (10.8%) in the 1-day group and nine (8.1%) in the 3-day group (odds ratio: 1.37; 95% confidence interval: 0.56-3.33; p = 0.48). By logistic regression analysis, 1-day prophylaxis with cefazolin was not associated with higher risk of SSI (adjusted odds ratio: 0.91; 95% confidence interval: 0.32-2.56; p = 0.85).Conclusion: Antibiotic prophylaxis for 1 day in CABG surgery was associated with similar rates of postoperative infection compared with antibiotic prophylaxis of 3 days. Copyright (C) 2011, Elsevier Taiwan LLC & Formosan Medical Association. All rights reserved.
Objective—We examined the effect of thrombomodulin (TM) domains 2 and 3 (TMD23) on human early endothelial progenitor cells (EPCs). Methods and Results—TM was expressed and released by human EPCs cultured from peripheral blood mononuclear cells (PBMCs). Addition of TMD23 (100 ng/mL) to the cultured PBMCs increased the colony-forming units, chemotactic motility, matrix metalloproteinase activity, and interleukin-8 secretion but decreased tumor necrosis factor-&agr; (TNF-&agr;) release. Analysis of the signal pathway showed that TMD23 activated Akt. Inhibition of phosphatidylinositol-3 kinase–Akt blocked the effects of TMD23 on chemotactic motility, matrix metalloproteinase-9, interleukin-8, and TNF-&agr;. In hindlimb ischemia mice, laser Doppler perfusion imaging of the ischemic limb during the 21 days after arterial ligation showed that the perfusion recovered best with intraperitoneal infusion of TMD23 plus local injection of early EPCs, followed by either infusion of TMD23 or injection of the cells. Animals without either treatment had the worst results. Animals treated with TMD23 also had lower circulating and tissue levels of TNF-&agr;. Conclusion—TM is expressed and released by human circulating EPCs. Exogenous TMD23 enhances the angiogenic potential of early EPCs in vitro through activation of phosphatidylinositol-3 kinase-Akt pathway. Coadministration of TMD23 plus early EPCs augments therapeutic angiogenesis of the EPCs in ischemic tissues.
Aim: Extracorporeal cardiopulmonary resuscitation (ECPR) has been shown to have survival benefit over conventional CPR (CCPR) in patients with in-hospital cardiac arrest of cardiac origin. We compared the survival of patients who had return of spontaneous beating (ROSB) after ECPR with the survival of those who had return of spontaneous circulation (ROSC) after conventional CPR.Methods: Propensity score-matched cohort of adults with in-hospital prolonged CPR (>10 min) of cardiac origin in a university-affiliated tertiary extracorporeal resuscitation center were included in this study. Fifty-nine patients with ROSB after ECPR and 63 patients with sustained ROSC by CCPR were analyzed. Main outcome measures were survival at hospital discharge, 30 days, 6 months, and one year, and neurological outcome.Results: There was no statistical difference in survival to discharge (29.1% of ECPR responders vs. 22.2% of CCPR responders, p = 0.394) and neurological outcome at discharge and one year later. In the propensity score-matched groups, 9 out of 27 ECPR patients survived to one month (33.3%) and 7 out of 27 CCPR patients survived (25.9%). Survival analysis showed no survival difference (HR: 0.856, p = 0.634, 95% CI: 0.453-1.620) between the groups, either at 30 days or at the end of one year (HR: 0.602, p = 0.093, 95% CI: 0.333-1.088).Conclusions: This study failed to demonstrate a survival difference between patients who had ROSB after institution of ECMO and those who had ROSC after conventional CPR. Further studies evaluating the role of ECMO in conventional CPR rescued patients are warranted. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
Blood supply to the lungs is through extensive connection in the pulmonary and bronchial circulation.1 The bronchial circulation is responsible for approximately 1% of lung perfusion, and its main function is nutrition of the pulmonary structure.2-4 Connections between the pulmonary and bronchial circulation are particularly important when the pulmonary arterial circulation is lacking. In the long term, the bronchial circulation may dilate and support the functions of the affected areas.5-9
Objectives: We examined the role of atrial gap junctions, NF-κB and fibrosis in the occurrence of postoperative atrial fibrillation (AF) in patients undergoing coronary artery bypass graft (CABG) surgery. Methods: Forty-five patients with sinus rhythm were randomly assigned to the beating heart (n = 22) or cardioplegic cardiac arrest (n = 23) technique for surgery. Of them, 14 patients experienced post-CABG AF. Atrial samples taken before and after CABG surgery were analyzed. Results: During surgery, Cx43 and Cx40 proteins were significantly reduced (both p < 0.05) in the arrested heart group, but only mildly decreased in the beating heart group. However, the change of either connexin was not associated with AF. In contrast, patients with AF had a higher baseline expression of NF-κB and more fibrosis compared to those without AF (both p < 0.05). Conclusions: CABG surgery with the beating heart technique attenuated the reduction of atrial Cx43 and Cx40 compared to the cardioplegic cardiac arrest technique. Atrial inflammation and fibrosis status before surgery, but not the changes of connexins during surgery, were associated with the occurrence of post-CABG AF.
OBJECTIVE:Clinical improvement after a surgical ventricular restoration for ischemic cardiomyopathy is increasingly accepted by clinicians, but the mechanism is not completely understood.METHODS:Ten patients with ischemic cardiomyopathy underwent detailed magnetic resonance imaging for ventricular function before and 6 weeks after surgical ventricular restoration. Surgical procedures included combinations of coronary artery bypass grafting, restrictive mitral annuloplasty, and endoventricular patch plasty. Magnetic resonance imaging analysis included quantification of global and regional systolic function. Anterior and posterior left ventricular regions were divided by an imaginary plane (C-plane) determined from anterior mitral point and both papillary roots.RESULTS:Global stroke volume index increased from 28.8 +/- 4.9 mL/m(2) to 36.5 +/- 8.6 mL/m(2) after surgical ventricular restoration (P = .010) and seemed more related to increased posterior stroke volume index (15.9 +/- 4.3 mL/m(2) preoperatively, 21.8 +/- 3.9 mL/m(2) postoperatively, P = .001) than to changed anterior stroke volume index (15.9 +/- 4.4 mL/m(2) preoperatively, 18.2 +/- 6.9 mL/m(2) postoperatively, P = .369). C-plane area decreased only a little in diastole (37.7 +/- 8.3 cm(2) preoperatively, 32.9 +/- 5.9 cm(2) postoperatively, P = .119) but significantly in systole (31.5 +/- 9.4 cm(2) preoperatively, 23.7 +/- 7.6 cm(2) postoperatively, P = .023). This indicates functional recovery of border zone by restrictive endoventricular patch plasty.CONCLUSION:Rebuilding geometric normality by surgical ventricular restoration improves contractility of myocardium in border-zone and remote regions, resulting in increased stroke volume index from the posterior left ventricle.
Objectives: To examine the incidence and risk factors of intraprosthetic thrombotic deposits in abdominal aortic endografts.Methods: The clinical records of 51 patients (44 mates; mean age 76.3 years, range: 63-90 years) with abdominal aortic aneurysm treated with transfemoral implantation of bifurcated stent graft between the years 2002 and 2008 were retrospectively reviewed. Patients underwent three-phase helical computed tomographic (CT) examinations at 1-, 3-, 6- and 12-month intervals and then annually. The formation of intraprosthetic thrombus associated with use of anti-platelet, preoperative mural thrombus in the aneurysm, ratio of cross-sectional area between the mainbody and bilateral limb grafts and length of mainbody were evaluated.Results: Over a 10-month mean follow-up, intraluminal deposits of thrombotic material were observed in eight of 51 patients (15.6%, 95% confidence interval: 8.2-28). The first signs of thrombus formation occurred on average 9.8 months after endografting (range: 1-24 months). Intraprosthetic thrombotic deposits was not related to preoperative mural thrombus formation (p = 0.38) or postoperative anti-ptatelet or anticoagulation medication (p = 0.40). However, it was significantly related to the ratio of the cross-sectional area between the mainbody and the bilateral limb grafts and the length of mainbody (p = 0.04 and p = 0.01). There were three graft limbs occlusion owing to kinking with no intraprosthetic thrombus detected on CT scans taken prior to occlusion. One patient developed distal left proximal superior femoral artery embolisation 4 months after detectable intraprosthetic mainbody thrombus in a CT scan follow-up. In no case did the thrombotic deposits clear completely from the prosthesis lumen during follow-up.Conclusions: This short experience demonstrates that incidentally found thrombotic deposits in abdominal aortic endografts are common. The deposition of thrombus is mostly influenced by the geometry of the aortic stent graft with wider mainbody diameter coupled with smaller limb grafts and longer mainbody graft. Most of these thrombi are clinically silent and require no additional treatment. (C) 2009 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
Background: Whether off-pump coronary artery bypass grafting has a late renal protective advantage over conventional coronary arterial bypass grafting with cardiopulmonary bypass use is controversial. Methods: From 1997 to 2004, 2102 cases of isolated coronary arterial bypass grafting were collected and analyzed, 1116 (53%) in the cardiopulmonary bypass group and 986 (47%) in the off-pump coronary artery bypass grafting group. Cases were stratified by preoperative estimated glomerular filtration rate into three renal groups: 1012 (48%) in group 1, with glomerular filtration rates > 60 ml/h, 864 (41%) in group 2, with glomerular filtration rates of 30-60 ml/h, and 226 (10.8%) in group 3, with glomerular filtration rates < 30 ml/h, but without dialysis before surgery. Results: The in-hospital mechanical renal replacement therapy rates were 2.0%, 4.6%, and 26.1%, respectively, for the three renal groups that underwent coronary artery bypass grafting with conventional cardiopulmonary bypass, and 1.1%, 3.4%, and 14.0%, respectively for the three renal groups that underwent off-pump coronary artery bypass grafting. After risk adjustment, cardiopulmonary bypass use did not show statistical significance for in-hospital mechanical renal replacement therapy (p = 0.314, 0.524, 0.150, respectively, across renal groups 1-3). At the end of the 4-year follow-up period, 99.1%, 97.2%, and 78.6%, respectively, of patients were free of mechanical renal replacement therapy across the three renal groups (p = 0.0097 between renal groups 1 and 2; p < 0.001 between renal groups 2 and 3). Cox regression analysis for renal groups 2 and 3 revealed that cardiopulmonary bypass use was not a risk factor for mid-term mechanical renal replacement therapy (p = 0.452), but preoperative glomerular filtration rate, hypercholesterolemia, insulin-requiring diabetes, young age at surgery, female gender, and in-hospital mechanical renal replacement therapy use were. Conclusion: Patient characteristics, rather than operative strategy of using off-pump or conventional coronary artery bypass grafting, influence the mid-term mechanical renal replacement therapy rate for patients with glomerular filtration rates < 60 ml/min. (c) 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
BACKGROUND:Infected aneurysm of the aorta is almost always fatal without undergoing aortic resection. Medical treatment was attempted selectively in patients who were considered too high risk for surgery. We review our experience with 22 patients treated without undergoing aortic resection over 12 years. METHODS:Retrospective chart review. RESULTS:Between 1995 and 2007, 22 cases of infected aortic aneurysms treated without undergoing aortic resection during the first admission were included. There were 17 men with a median age of 76 years (range, 35 to 88 years). Of 18 pathogens isolated, the most common responsible microorganism was nontyphoid Salmonella in 11 followed by Staphylococcus aureus in five. The site of infection was thoracic in eight and abdominal in 14. The hospital mortality rate was 50%, and the aneurysm-related mortality rate after long-term follow-up was 59%. The event-free survival rate at one year was 32%. Of 11 patients with Salmonella infection, eight patients have lived beyond 30 days and six were event-free after one year. Of 11 patients with non-Salmonella, four patients have lived beyond 30 days and only one was event-free after one year. The overall aneurysm-related mortality rate was 36% in Salmonella infected patients and 82% in non-Salmonella infected patients. CONCLUSION:Clinical results of medical treatment using current antibiotics in patients with infected aortic aneurysm were poor. Traditional surgical excision of infected aortic aneurysms with revascularization remains the gold standard and should be attempted except in high risk patients.
OBJECTIVES:To evaluate the use of extracorporeal membrane oxygenation in prolonged cardiopulmonary resuscitation and to estimate how long cardiopulmonary resuscitation can be extended with acceptable results. DESIGN:Review of consecutive adult in-hospital cardiopulmonary resuscitation patients without return of spontaneous circulation in 10 mins and with extracorporeal membrane oxygenation rescue, and analysis of the relationship between outcome and cardiopulmonary resuscitation duration and possible etiologies. The data were collected following the Utstein style guidelines on in-hospital cardiopulmonary resuscitation. Two organ dysfunction scores were incorporated into the analysis for outcome prediction. SETTING:A university-affiliated tertiary referral medical center and extracorporeal membrane oxygenation center. PATIENTS:An observational cohort study in 135 consecutive adult in-hospital cardiopulmonary resuscitation patients without return of spontaneous circulation who received extracorporeal membrane oxygenation during cardiopulmonary resuscitation. MAIN RESULTS:The average cardiopulmonary resuscitation duration was 55.7 +/- 27.0 mins and 56.3% of patients received subsequent interventions to treat underlying etiologies. The successful weaning rate was 58.5% and the survival-to-discharge rate was 34.1%. The majority of survivors (89%) had an acceptable neurologic status on discharge. Risk factors for hospital mortality included longer cardiopulmonary resuscitation duration, etiology of acute coronary syndrome, and a higher organ dysfunction score in the first 24 hrs. Logistic regression analysis revealed the probability of survival was approximately 0.5, 0.3, or 0.1 when the duration of cardiopulmonary resuscitation was 30, 60, or 90 mins, respectively. CONCLUSION:Assisted circulation might extend the presently accepted duration of cardiopulmonary resuscitation in adult in-hospital cardiopulmonary resuscitation patients.
Objective: Liver cirrhosis is considered to be a contraindication to heart transplantation. However, the clinical outcome of heart transplantation in patients with liver cirrhosis has not been reported. Here, we sought to evaluate the clinical outcome of heart transplantation in cirrhotic patients. Methods: Data were collected by retrospective chart review. Patients with liver cirrhosis at the time of transplantation were included. Results: Between 1987 and 2007, 12 patients with liver cirrhosis underwent heart transplantation at the authors' hospital. Diagnosis of liver cirrhosis was based on preoperative abdominal sonography in five, autopsy in five, and laparotomy in two patients. Causes of heart failure were dilated cardiomyopathy in four, coronary artery disease in three, congenital heart disease in three and valvular heart disease in two patients. Causes of liver cirrhosis were alcoholism in two, cardiac in seven, and unknown in three patients. The Child classification was class A in three, class B in five and class C in four patients. Overall, the hospital mortality rate was 50% and major in-hospital complications occurred in nine patients (75%). Patients with non-cardiomyopathy diagnosis, previous sternotomy, and massive ascites had a high hospital mortality rate. The median follow-up duration was 33.5 months. There was no late death. Late post-transplant complications occurred in four patients and there was no event of liver dysfunction. All survivors were in Child class A at outpatient follow-up. Conclusions: Although there was high mortality and morbidity, patients with end-stage heart failure and liver cirrhosis can be considered for heart transplantation with careful case selection. (C) 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
Background Extracorporeal life-support as an adjunct to cardiac resuscitation has shown encouraging outcomes in patients with cardiac arrest. However, there is little evidence about the benefit of the procedure compared with conventional cardiopulmonary resuscitation (CPR), especially when continued for more than 10 min. We aimed to assess whether extracorporeal CPR was better than conventional CPR for patients with in-hospital cardiac arrest of cardiac origin.Methods We did a 3-year prospective observational study on the use of extracorporeal life-support for patients aged 18-75 years with witnessed in-hospital cardiac arrest of cardiac origin undergoing CPR of more than 10 min compared with patients receiving conventional CPR. A matching process based on propensity-score was done to equalise potential prognostic factors in both groups, and to formulate a balanced 1:1 matched cohort study. The primary endpoint was survival to hospital discharge, and analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00173615.Findings Of the 975 patients with in-hospital cardiac arrest events who underwent CPR for longer than 10 min, 113 were enrolled in the conventional CPR group and 59 were ertrolled in the extracorporeal CPR group. Unmatched patients who underwent extracorporeal CPR had a higher survival rate to discharge (log-rank p<0 . 0001) and a better 1-year survival than those who received conventional CPR (log rank p=0.007). Between the propensity-score matched groups, there was still a significant difference in survival to discharge (hazard ratio [HR] 0. 51, 95% CI 0.35-0.74, p<0.0001), 30-day survival (HR 0 .47, 95% CI 0 . 28-0.77, p=0.003), and 1-year survival (HR 0.53, 95% Cl 0.33-0.83, p=0.006) favouring extracorporeal CPR over conventional CPR.Interpretation Extracorporeal CPR had a short-term and long-term survival benefit over conventional CPR in patients with in-hospital cardiac arrest of cardiac origin.Funding National Science Council, Taiwan.
OBJECTIVE:Both ventilations and compressions are important for victims of prolonged cardiopulmonary resuscitation (CPR) and asphyxial arrest. Dispatch assistance increases bystander CPR, but the quality of dispatcher-assisted CPR (DA-CPR), especially rescue breathing, remains unsatisfactory. This study was conducted to assess the impact of adding interactive video communication to dispatch instructions on the quality of rescue breathing in simulated cardiac arrests.METHODS:In this simulation-based study, adults without CPR training within 5 years were recruited between April and July 2007 and randomized to receive dispatch assistance with either voice instruction alone (voice group, n=53) or interactive voice and video instruction (video group, n=43) via a video cell phone. The quality of rescue breathing was evaluated by reviewing the videos and mannequin reports.RESULTS:Subjects in the video group were more likely to open the airway correctly (95.3% vs. 58.5%, P<0.01) and to lift the chin properly (95.3% vs. 62.3%, P<0.01), but had similar rates of head-tilt (95.3% vs. 84.9%, P=0.10). Volunteers in the video group had larger volume of ventilation (median volume 540 ml vs. 0 ml, P<0.01), greater possibility to sustain an open airway (88.4% vs. 60.4%, P<0.01) and a tendency towards better nose-pinch (97.7% vs. 86.8%, P=0.06). The video group spent longer time to open the airway (59 s vs. 56 s, P<0.05) and to give the first rescue breathing (139 s vs. 102 s, P<0.01).CONCLUSION:Adding video communication to dispatch instructions improved the quality of bystander rescue breathing, including higher proportion of airway opened, and larger volume of ventilation delivered, in simulated cardiac arrests.