Considering Burnout and Well-Being: Emergency Medicine Resident Shift Scheduling Platform and Satisfaction Insights from a Quality Improvement Project.

Few studies explore emergency medicine (EM) residency shift scheduling software as a mechanism to reduce administrative demands and broader resident burnout. A local needs assessment demonstrated a learning curve for chief resident schedulers and several areas for improvement. In an institutional quality improvement project, we utilized an external online cross-sectional convenience sampling pilot survey of United States EM residency programs to collect information on manual versus software-based resident shift scheduling practices and associated scheduler and scheduler-perceived resident satisfaction. Our external survey response rate was 19/253 (8%), with all United States regions (i.e., northeast, southeast, midwest, west, and southwest) represented. Two programs (11%) reported manual scheduling without any software. ShiftAdmin was the most popularly reported scheduling software (53%). Although not statistically significant, manual scheduling had the lowest satisfaction score and programs with ≤30 residents reported the highest levels of satisfaction. Our data suggest that improvements in existing software-based technologies are needed. Artificial intelligence technologies may prove useful for reducing administrative scheduling demands and optimizing resident scheduling satisfaction.

The test developer's dilemma: Evaluating the balance of feasibility and empiric performance of test development techniques for repeated written assessments.

PURPOSE: Written assessments face challenges when administered repeatedly, including resource-intensive item development and the potential for performance improvement secondary to item recall as opposed to understanding. This study examines the efficacy of three-item development techniques in addressing these challenges. METHODS: Learners at five training programs completed two 60-item repeated assessments. Items from the first test were randomized to one of three treatments for the second assessment: (1) Verbatim repetition, (2) Isomorphic changes, or (3) Total revisions. Primary outcomes were the stability of item psychometrics across test versions and evidence of item recall influencing performance as measured by the rate of items answered correctly and then incorrectly (correct-to-incorrect rate), which suggests guessing. RESULTS: Forty-six learners completed both tests. Item psychometrics were comparable across test versions. Correct-to-incorrect rates differed significantly between groups with the highest guessing rate (lowest recall effect) in the Total Revision group (0.15) and the lowest guessing rate (highest recall effect) in the Verbatim group (0.05), p = 0.01. CONCLUSIONS: Isomorphic and total revisions demonstrated superior performance in mitigating the effect of recall on repeated assessments. Given the high costs of total item revisions, there is promise in exploring isomorphic items as an efficient and effective approach to repeated written assessments.[Box: see text].

Evidence according to Cochrane Systematic Reviews on Alterable Risk Factors for Anastomotic Leakage in Colorectal Surgery.

Anastomotic leakage reflects a major problem in visceral surgery, leading to increased morbidity, mortality, and costs. This review is aimed at evaluating and summarizing risk factors for colorectal anastomotic leakage. A generalized discussion first introduces risk factors beginning with nonalterable factors. Focus is then brought to alterable impact factors on colorectal anastomoses, utilizing Cochrane systematic reviews assessed via systemic literature search of the Cochrane Central Register of Controlled Trials and Medline until May 2019. Seventeen meta-anaylses covering 20 factors were identified. Thereof, 7 factors were preoperative, 10 intraoperative, and 3 postoperative. Three factors significantly reduced the incidence of anastomotic leaks: high (versus low) surgeon's operative volume (RR = 0.68), stapled (versus handsewn) ileocolic anastomosis (RR = 0.41), and a diverting ostomy in anterior resection for rectal carcinoma (RR = 0.32). Discussion of all alterable factors is made in the setting of the pre-, intra-, and postoperative influencers, with the only significant preoperative risk modifier being a high colorectal volume surgeon and the only significant intraoperative factors being utilizing staples in ileocolic anastomoses and a diverting ostomy in rectal anastomoses. There were no measured postoperative alterable factors affecting anastomotic integrity.

rhIGF-1/BP3 Preserves Lung Growth and Prevents Pulmonary Hypertension in Experimental Bronchopulmonary Dysplasia.

Rationale: Antenatal factors, such as chorioamnionitis, preeclampsia, and postnatal injury, are associated with an increased risk for bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH) after preterm birth. IGF-1 (insulin-like growth factor-1) is markedly decreased in normal preterm infants, but whether IGF-1 treatment can prevent BPD or PH is unknown.Objectives: To evaluate whether postnatal treatment with rhIGF-1 (recombinant human IGF-1)/BP3 (binding peptide 3) improves lung growth and prevents PH in two antenatal models of BPD induced by intraamniotic exposure to endotoxin (ETX) or sFlt-1 (soluble fms-like tyrosine kinase 1), and in a postnatal model due to prolonged hyperoxia.Methods: ETX or sFlt-1 were administered into the amniotic sac of pregnant rats at Embryonic Day 20 to simulate antenatal models of chorioamnionitis and preeclampsia, respectively. Pups were delivered by cesarean section at Embryonic Day 22 and treated with rhIGF-1/BP3 (0.02-20 mg/kg/d intraperitoneal) or buffer for 2 weeks. Study endpoints included radial alveolar counts (RACs), vessel density, and right ventricular hypertrophy (RVH). Direct effects of rhIGF-1/BP3 (250 ng/ml) on fetal lung endothelial cell proliferation and tube formation and alveolar type 2 cell proliferation were studied by standard methods in vitro.Measurements and Main Results: Antenatal ETX and antenatal sFlt-1 reduced RAC and decreased RVH in infant rats. In both models, postnatal rhIGF-1/BP3 treatment restored RAC and RVH to normal values when compared with placebo injections. rhIGF-1/BP3 treatment also preserved lung structure and prevented RVH after postnatal hyperoxia. In vitro studies showed that rhIGF-1/BP3 treatment increased lung endothelial cell and alveolar type 2 cell proliferation.Conclusions: Postnatal rhIGF-1/BP3 treatment preserved lung structure and prevented RVH in antenatal and postnatal BPD models. rhIGF-1/BP3 treatment may provide a novel strategy for the prevention of BPD in preterm infants.

Single Incision Pediatric Endoscopic Surgery: From Myth to Reality a Case Series.

Laparoscopic surgery has continued to evolve to minimize access sites and scars in both the adult and pediatric populations. In children, single-incision pediatric endoscopic surgery (SIPES) has been shown to be effective, feasible, and safe with comparative results to multiport equivalents. Thus, the use of SIPES continues over increasingly complex cases, however, conceptions of its efficacy continue to vary greatly. In the present case series and discussion, we review the history of SIPES techniques and its current application today. We present this in the setting of five common myths about SIPES techniques: limitations against complex cases, restrictions to specialized training, increased morbidity outcomes, increased operative lengths, and increased operative costs. Regarding the myth of SIPES being limited in application to simple cases, examples were highlighted throughout the literature in addition to the authors' own experience with three complex cases including resection of a lymphatic malformation, splenectomy with cholecystectomy, and distal pancreatectomy with splenectomy. A review of SIPES learning curves shows equivalent operative outcomes to multiport learning curves and advancements towards practical workshops to increase trainee familiarity can help assuage these aptitudes. In assessing comorbidities, adult literature reveals a slight increase in incisional hernia rates, but this does not correlate with single-incision pediatric data. In experienced hands, operative SIPES times average approximate multiport laparoscopic equivalents. Finally, regarding expenses, SIPES represents an equivalent alternative to laparoscopic techniques.

Gene characteristics predicting missense, nonsense and frameshift mutations in tumor samples.

BACKGROUND: Because driver mutations provide selective advantage to the mutant clone, they tend to occur at a higher frequency in tumor samples compared to selectively neutral (passenger) mutations. However, mutation frequency alone is insufficient to identify cancer genes because mutability is influenced by many gene characteristics, such as size, nucleotide composition, etc. The goal of this study was to identify gene characteristics associated with the frequency of somatic mutations in the gene in tumor samples. RESULTS: We used data on somatic mutations detected by genome wide screens from the Catalog of Somatic Mutations in Cancer (COSMIC). Gene size, nucleotide composition, expression level of the gene, relative replication time in the cell cycle, level of evolutionary conservation and other gene characteristics (totaling 11) were used as predictors of the number of somatic mutations. We applied stepwise multiple linear regression to predict the number of mutations per gene. Because missense, nonsense, and frameshift mutations are associated with different sets of gene characteristics, they were modeled separately. Gene characteristics explain 88% of the variation in the number of missense, 40% of nonsense, and 23% of frameshift mutations. Comparisons of the observed and expected numbers of mutations identified genes with a higher than expected number of mutations- positive outliers. Many of these are known driver genes. A number of novel candidate driver genes was also identified. CONCLUSIONS: By comparing the observed and predicted number of mutations in a gene, we have identified known cancer-associated genes as well as 111 novel cancer associated genes. We also showed that adding the number of silent mutations per gene reported by genome/exome wide screens across all cancer type (COSMIC data) as a predictor substantially exceeds predicting accuracy of the most popular cancer gene predicting tool - MutsigCV.

Anti-sFlt-1 Therapy Preserves Lung Alveolar and Vascular Growth in Antenatal Models of Bronchopulmonary Dysplasia.

RATIONALE: Pregnancies complicated by antenatal stress, including preeclampsia (PE) and chorioamnionitis (CA), increase the risk for bronchopulmonary dysplasia (BPD) in preterm infants, but biologic mechanisms linking prenatal factors with BPD are uncertain. Levels of sFlt-1 (soluble fms-like tyrosine kinase 1), an endogenous antagonist to VEGF (vascular endothelial growth factor), are increased in amniotic fluid and maternal blood in PE and associated with CA. OBJECTIVES: Because impaired VEGF signaling has been implicated in the pathogenesis of BPD, we hypothesized that fetal exposure to sFlt-1 decreases lung growth and causes abnormal lung structure and pulmonary hypertension during infancy. METHODS: To test this hypothesis, we studied the effects of anti-sFlt-1 monoclonal antibody (mAb) treatment on lung growth in two established antenatal models of BPD that mimic PE and CA induced by intraamniotic (i.a.) injections of sFlt-1 or endotoxin, respectively. In experimental PE, mAb was administered by three different approaches, including antenatal treatment by either i.a. instillation or maternal uterine artery infusion, or by postnatal intraperitoneal injections. RESULTS: With each strategy, mAb therapy improved infant lung structure as assessed by radial alveolar count, vessel density, right ventricular hypertrophy, and lung function. As found in the PE model, the adverse lung effects of i.a. endotoxin were also reduced by antenatal or postnatal mAb therapy. CONCLUSIONS: We conclude that treatment with anti-sFlt-1 mAb preserves lung structure and function and prevents right ventricular hypertrophy in two rat models of BPD of antenatal stress and speculate that early mAb therapy may provide a novel strategy for the prevention of BPD.

Late complications of biliary atresia: hepatopulmonary syndrome and portopulmonary hypertension.

Children with biliary atresia (BA) following Kasai portoenterostomy have a high risk for portal hypertension, however, while variceal and hemorrhagic complications have been more commonly studied, less frequent but no less possibly devastating complications of hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPH) remain less well understood. HPS and PPH both occur in a setting of portal hypertension, however, paradoxically patients with HPS develop pulmonic vasculature dilation leading to shunting and hypoxia, while those with PPH develop an opposite progression of pulmonary vasoconstriction eventually leading to cor pulmonale and decompensation. Given the near diametric evolution of diseases, HPS and PPH differ widely in therapy, though liver transplantation can have a role for treatment in either disease state. We reviewed our series of 320 pediatric patients with biliary atresia treated at our institution over 44 years, highlighting two cases that developed HPS and PPH, respectively, using these cases in further discussion of hepatopulmonary syndrome and portopulmonary hypertension regarding disease etiology, diagnosis, management, and prognosis. The complicated nature of these processes demand a careful multidisciplinary approach to optimize patient outcomes, including mindful evaluation for when transplantation may offer benefit.

Catheter-based endomyocardial delivery of mesenchymal precursor cells using 3D echo guidance improves cardiac function in a chronic myocardial injury ovine model.

The administration of bone marrow-derived stem cells may provide a new treatment option for patients with heart failure. Transcatheter cell injection may require multi-imaging modalities to optimize delivery. This study sought to evaluate whether endomyocardial injection of mesenchymal precursor cells (MPCs) could be guided by real-time 3D echocardiography (RT3DE) in treating chronic, postinfarction (MI) left ventricular (LV) dysfunction in sheep. Four weeks after induction of an anterior wall myocardial infarction in 39 sheep, allogeneic MPCs in doses of either 25 × 10(6) (n = 10), 75 × 10(6) (n = 9), or 225 × 10(6) (n = 10) cells or nonconditioned control media (n = 10) were administered intramyocardially into infarct and border zone areas using a catheter designed for combined fluoroscopic and RT3DE-guided injections. LV function was assessed before and after injection. Infarct dimension and vascular density were evaluated histologically. RT3DE-guided injection procedures were safe. Compared to controls, the highest dose MPC treatment led to increments in ejection fraction (3 ventricula 3% in 225M MPCs vs. -5 ± 4% in the control group, p < 0.01) and wall thickening in both infarct (4 ± 4% in 225M MPCs vs. -3 ± 6% in the control group, p = 0.02) and border zones (4 ± 6% in 225M MPCs vs. -8 ± 9% in the control group, p = 0.01). Histology analysis demonstrated significantly higher arteriole density in the infarct and border zones in the highest dose MPC-treated animals compared to the lower dose or control groups. Endomyocardial implantation of MPCs under RT3DE guidance was safe and without observed logistical obstacles. Significant increases in LV performance (ejection fraction and wall thickening) and neovascularization resulted from this technique, and so this technique has important implications for treating patients with postischemic LV dysfunction.

Correlation of angiographic late loss with neointimal proliferation in stents evaluated by OCT and histology in porcine coronary arteries.

OBJECTIVES: We aimed to evaluate the correlation of angiographic late loss (LL) with the degree of in-stent neointimal proliferation assessed by optical coherence tomography (OCT) and histology. BACKGROUND: Angiographic LL is the most common endpoint used in clinical trials for the evaluation of the efficacy of drug-eluting stents (DES). However, there are few data in regards to the accuracy of angiographic LL in the evaluation of DES displaying lower degrees of neointimal proliferation. METHODS: A total of 49 stents (36 DES and 13 bare-metal stents) were deployed in coronary arteries of 23 domestic swine and followed up for 28 or 90 days, thus obtaining different degrees of neointimal proliferation. Each stent was divided into 8 to 9 segments along the longitudinal axis to match corresponding histological cross sections. Angiographic LL was calculated at each segment throughout the entire length of the stent and compared with in-stent neointimal thickness (NT) obtained by OCT and histology. RESULTS: A total of 382 angiographic segments were suitable for matched comparison with both OCT and histological findings. The mean LL at follow-up was 0.60 ± 0.57 mm (range: -0.46 to 2.3 mm) for all segments. Approximately 13.9% of stent segments had a LL between -0.5 and 0 mm, and 22.5% had a LL greater than 1.0 mm. The correlation between OCT and histology for the evaluation of NT was adequate regardless the level of angiographic LL. In addition, overall correlations between angiographic LL and NT by OCT or histology were adequate (R = 0.77 and 0.63, respectively). However, angiographic LL showed a poor correlation with NT by OCT or histology at a value <0.55 mm (R = 0.38 and 0.15, respectively). CONCLUSIONS: Angiographic LL below a threshold value of 0.55 mm correlates poorly with NT obtained by OCT and histology. These results suggest a cautious interpretation is needed to evaluate angiographic endpoints in DES trials in which LL values below this threshold are reported.

Cardiomyocyte differentiation of bone marrow-derived Oct-4+CXCR4+SSEA-1+ very small embryonic-like stem cells.

VSELs are a population of rare Oct-4+CXCR4+ CD133+lin-CD45- cells that are deposited during early embryogenesis in developing organs/tissues as a reserve population of pluripotent stem cells for regeneration. We reported recently that they are mobilized into peripheral blood during acute myocardial infarction (AMI) in mice and humans. However, although freshly isolated VSELs in experimental AMI mouse models improve cardiac function, the number of these cells is limited and an ex vivo expansion strategy is needed to employ these cells more efficiently for cardiac regeneration. The aim of this study was to establish an efficient method to expand ex vivo BM-derived very small embryonic-like stem cells (VSELs) into cardiomyocytes. VSELs, highly purified by FACS from the bone marrow of GFP transgenic mice, were expanded over C2C12 cell line myoblasts and exposed to cardiac differentiating media. The changes in gene expression during cardiac differentiation of VSELs were evaluated by RTQ-PCR, immunostaining and gene array analysis. We developed an efficient, two-step, ex vivo expansion/differentiation model of BM-derived VSELs into cardiomyocytes. First, purified GFP+ VSELs are plated over C2C12 murine cell line myoblasts, where they expand and differentiate into characteristic spheres. Subsequently, cells from these spheres are expanded on cardiac differentiating media into cardiomyocytes. This study demonstrates that murine BM-derived VSELs can be efficiently expanded in vitro and differentiated into cardiomyocytes.

Impact of adventitial neovascularisation on atherosclerotic plaque composition and vascular remodelling in a porcine model of coronary atherosclerosis.

AIMS: There is little in vivo data in regards to the impact of adventitial neovascularisation on vascular remodelling and plaque composition. Using a porcine model of coronary atherosclerosis, we aimed to determine the impact of adventitial neovascularisation on plaque composition and vascular remodelling evaluated by IVUS. METHODS AND RESULTS: Coronary atherosclerosis was induced by adventitial delivery of lipids and a high cholesterol diet. At termination all vessels were analysed using IVUS to determine the degree of remodelling of each individual segment containing atherosclerotic lesions. Then, each segment was correlated with its correspondent histological frame for plaque composition and neovessel density. A total of 57 atherosclerotic lesions at different stages of development were analysed. The total neovessel count (TNC) correlated to the degree of plaque burden (15.6+/-7.2 TNC in <40% stenosis versus 35.7+/-14.0 TNC in >60% stenosis, p<0.01) and to the amount of intra-plaque collagen (32.4+/-14.1%, lower TNC tertile versus 47.5+/-8.9% upper TNC tertile, p< 0.01). The amount of intra-plaque SMC content inversely correlated with the TNC (49.7+/-18.9% versus 36.4+/-14.4%, lower versus upper tertiles, p<0.05). Plaques with the highest TNC showed higher remodelling indexes by IVUS (0.89+/-0.32 in lower TNC tertile versus 1.36+/-0.73 in upper TNC tertile, p<0.05) and higher macrophage cell content (161.42+/-157.6 in lower TNC tertile versus 340.6+/-127.2 in upper TNC tertile, p<0.05) compared to non-remodelled segments. CONCLUSIONS: Adventitial neovascularisation is more prominent in positively remodelled segments and appears to be associated to SMC loss, increase collagen deposition and localised macrophage infiltration.

Unreliable assessment of necrotic core by virtual histology intravascular ultrasound in porcine coronary artery disease.

BACKGROUND: Intravascular ultrasound-derived virtual histology (VH IVUS) is used increasingly in clinical research to assess composition and vulnerability of coronary atherosclerotic lesions. However, the ability of VH IVUS to quantify individual plaque components, in particular the size of the destabilizing necrotic core, has never been validated. We tested for correlation between VH IVUS necrotic core size and necrotic core size by histology in porcine coronary arteries with human-like coronary disease. METHODS AND RESULTS: In adult atherosclerosis-prone minipigs, 18 advanced coronary lesions were assessed by VH IVUS in vivo followed by postmortem microscopic examination (histology). We found no correlation between the size of the necrotic core determined by VH IVUS and histology. VH IVUS displayed necrotic cores in lesions lacking cores by histology. CONCLUSIONS: We found no correlation between necrotic core size determined by VH IVUS and real histology, questioning the ability of VH IVUS to detect rupture-prone plaques, so-called thin-cap fibroatheromas.

Development of a novel prohealing stent designed to deliver sirolimus from a biodegradable abluminal matrix.

BACKGROUND: We aimed to demonstrate that, by separating endothelial progenitor cell capture from sirolimus delivery through the application of drug to the abluminal surface of the stent, the degree of endothelialization can be enhanced. METHODS AND RESULTS: Stainless steel R Stents, with biodegradable SynBiosys polymer coating with sirolimus abluminally applied and surface modified with anti-CD34 antibody were prepared at 2 dosages (low-dose sirolimus [LD-Combo, 2.5 microg sirolimus/mm] and full-dose sirolimus [Combo, 5 microg sirolimus/mm). These Combo stents and the Cypher stent (10 microg sirolimus/mm) were deployed in 98 normal porcine arteries and harvested for pharmacokinetic analysis at 0.25, 1, 3, 7, 14, 28, and 35 days. The LD-Combo stents showed faster early release (50%total dose in 72 hours) than the Combo and Cypher. At 30 days, drug release was near complete with both Combo stents, whereas 20% of drug remained on the Cypher stents. To assess efficacy, a total of 50 stents (Xience V=8, Cypher=8, Genous bioengineered R stent=6, LD-Combo=14, and Combo=14) were implanted in 18 pigs for 14 and 28 days. Optical coherence tomography was performed, and stents were harvested for histology. At 28 days, there was less neointimal thickness with Combo (0.173+/-0.088 mm) compared with Cypher (0.358+/-0.225 mm), LD-Combo (0.316+/-0.228 mm), and Xience V (0.305+/-0.252 mm; P<0.00001). Immunohistochemical analysis of endothelialization showed that Genous bioengineered R stent had the highest degree of platelet endothelial cell adhesion molecule expression (87%) followed by the Combo (75%), LD-Combo (65%), and Cypher (58%). CONCLUSIONS: Both optical coherence tomography and histology demonstrate that anti-CD34 sirolimus-eluting stents promote endothelialization while reducing neointimal formation and inflammation.

Accuracy of optical coherence tomography in the evaluation of neointimal coverage after stent implantation.

OBJECTIVES: This study aimed to evaluate the accuracy of optical coherence tomography (OCT) in analyzing the neointimal response to several drug-eluting stent (DES) types by comparing OCT images acquired in vivo with corresponding histological specimens using a nondiseased porcine injury model. BACKGROUND: Optical coherence tomography is emerging as a promising endovascular imaging tool for the evaluation of neointimal response after DES implantation. METHODS: A total of 84 stents were implanted-22 ML Vision (Abbott Vascular, Santa Clara, California), 22 Xience V (Abbott Vascular), 20 Endeavor (Medtronic, Minneapolis, Minnesota), and 20 Taxus Liberté (Boston Scientific, Natick, Massachusetts) stents-in normal porcine coronary arteries and were harvested at 28 (n=42) and 90 (n=42) days, with the different stent types equally distributed between the 2 follow-up periods. At termination, morphometric evaluation using OCT imaging was performed in all stented arteries. Histological morphometric analysis was performed and correlated with OCT. RESULTS: A total of 622 OCT-histology matched frames acquired from all stent designs were analyzed. The luminal (13.7%) and stent (6.1%) areas were consistently larger by OCT compared with histology. The mean neointimal thickness was very similar between techniques (approximately 3.27% variation). There was a high correlation between OCT and histology for the evaluation of neointimal area (R2=0.804), luminal area (R2=0.825), and neointimal thickness (R2=0.789). Correlation for total stent area was poor (R2=0.352). Although the proportion of individual struts determined to be uncovered by OCT and histology was similar, there was significant variation in the estimation of strut coverage between OCT and histology when the neointimal thickness was between 20 and 80 microm. This variation converged for neointimal thicknesses between 80 and 100 microm. CONCLUSIONS: Subtle differences in neointimal formation induced by current DES can be reproducibly analyzed in vivo by OCT. However, OCT measurement of stent area seems to have less correlation with histology.

Patterns of activation and deposition of platelets exposed to the polymeric surface of the paclitaxel eluting stent.

The interaction of platelets with the polymeric surface of drug eluting stents has not been fully described in the literature. Our aim was to analyze the patterns of activation and deposition of platelets exposed to two different stent platforms; (a) the polymeric surface of the paclitaxel eluting stent (Taxus((R)) stent, PES,) and (b) the metallic surface of a stent with identical structural design (Express((R)) stent, BMS). Platelet activation was tested by deploying stents in an in vitro flow chamber model. Anticoagulated blood of 25 healthy volunteers was circulated (flow rate 10 ml/min for 60 min) into the flow chamber system. P-selectin expression, glycoprotein IIb/IIIa activation (PAC-1 binding) and platelet-monocyte complexes (PMC) formation were evaluated at 0, 10, 30 and 60 min. Surface platelet deposition was assessed by surface electron microscopy in stents implanted in the in vitro system for 60 min and in stents implanted in normal porcine coronary arteries for 24 h. Platelet activation evaluation showed a higher P-Selectin expression (92.9% of baseline in PES versus 68.3 % in BMS, P = 0.01) and higher PMC formation (125.7 % of baseline in PES versus 75.6% in BMS, P < 0.01) in the PES compared to the BMS control group. PAC-1 binding levels did not differ among groups. In the in vitro study, SEM analysis of the stent surface showed no statistical differences on platelet deposition between the groups. In addition, presence of proteinaceous material was more frequently seen on the BMS group (moderate to complete coverage = 80% in BMS versus 26% in PES, P < 0.01). In the in vivo study, complete platelet coverage was similar between groups (PES = 7% versus BMS = 8%, P = NS). However, there was an overall trend towards less platelet deposition on the BMS surface (mild and moderate coverage = 83%, 9% in BMS versus 49%, 44% in PES, P < 0.001 for both) but thrombus formation was not observed in either group. The polymeric surface of the PES appears to induce a higher degree of platelet activation and deposition compared to the BMS surface. The biological implications of these findings on the patterns of vascular healing need to be further studied in vivo. Condensed Abstract The interaction of human platelets with the surface of drug eluting stents has not been fully characterized. Patterns of platelet activation and adhesion were evaluated in vitro and in vivo after exposing platelets to the surface of the paclitaxel-eluting stent and identical bare metal stent. The degree of PMC formation and P-selectin expression was increased in PES compared to BMS. In the in vivo study, complete platelet coverage was similar between groups. There was an overall trend towards less platelet deposition on the BMS surface, however, thrombus formation was not observed on either surface. The polymeric surface of the PES appears to induce a higher degree of platelet activation and deposition compared to the BMS surface.

Early and long-term results of unprotected left main coronary artery stenting: the LE MANS (Left Main Coronary Artery Stenting) registry.

OBJECTIVES: The aim of the study was to evaluate early and late outcomes after percutaneous coronary intervention (PCI) of unprotected left main coronary artery disease (ULMCA) and to compare bare-metal stent (BMS) and drug-eluting stent (DES) subgroups. BACKGROUND: PCI is an increasingly utilized method of revascularization in patients with ULMCA. METHODS: This multicenter prospective registry included 252 patients after ULMCA stenting enrolled between March 1997 and February 2008. Non-ST-segment elevation acute coronary syndrome was diagnosed in 58% of patients; ST-segment elevation myocardial infarction cases were excluded. Drug-eluting stents were implanted in 36.2% of patients. RESULTS: Major adverse cardiovascular and cerebral events (MACCE) occurred in 12 (4.8%) patients during the 30-day period, which included 4 (1.5%) deaths. After 12 months there were 17 (12.1%) angiographically confirmed cases of restenosis. During long-term follow-up (1 to 11 years, mean 3.8 years) there were 64 (25.4%) MACCE and 35 (13.9%) deaths. The 5- and 10-year survival rates were 78.1% and 68.9%, respectively. Despite differences in demographical and clinical data in favor of BMS patients, unmatched analysis showed a significantly lower MACCE rate in DES patients (25.9% vs. 14.9%, p = 0.039). This difference was strengthened after propensity score matching. The DES lowered both mortality and MACCE for distal ULMCA lesions when compared with BMS. Ejection fraction <50% was the only independent risk factor influencing long-term survival. CONCLUSIONS: Stenting of ULMCA is feasible and offers good long-term outcome. Implantation of DES for ULMCA decreased the risk of long-term MACCE, and particularly improved survival in patients with distal ULMCA disease.

Survival of midbrain dopaminergic cells after lesion or deep brain stimulation of the subthalamic nucleus in MPTP-treated monkeys.

We have examined dopaminergic cell survival after alteration of the subthalamic nucleus (STN) in methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. The STN was lesioned with kainic acid (B series) or underwent deep brain stimulation (DBS) at high frequency (C series). In another series, MPTP-treated and non-MPTP-treated monkeys had no STN alteration (intact animals; A series). Animals were treated with MPTP either after (B1, C1) or before (B2, C2) STN alteration. We also explored the long-term ( approximately 7 months) effect of DBS in non-MPTP-treated monkeys (D series). Brains were aldehyde-fixed and processed for routine Nissl staining and tyrosine hydroxylase immunocytochemistry. Our results showed that there were significantly more (20-24%) dopaminergic cells in the substantia nigra pars compacta (SNc) of the MPTP-treated monkeys that had STN alteration, either with kainic acid lesion or DBS, compared to the non-MPTP-treated monkeys (intact animals). We suggest that this saving or neuroprotection was due to a reduction in glutamate excitotoxicity, as a result of the loss or reduction of the STN input to the SNc. Our results also showed that SNc cell number in the B1 and C1 series were very similar to those in the B2 and C2 series. In the cases that had long-term DBS of the STN (D series), there was no adverse impact on SNc cell number. In summary, these results indicated that STN alteration offered neuroprotection to dopaminergic cells that would normally die as part of the disease process.

SPECT imaging, immunohistochemical and behavioural correlations in the primate models of Parkinson's disease.

Dopamine active transporter (DAT) single photon emission computerised tomography (SPECT) is considered a useful and practical technique for early diagnosis of Parkinson's disease (PD) and assessment of its progression. The application of this technique, particularly as a surrogate marker for therapeutic and neuroprotective trials in Parkinsonism, however, is dependent on pathological validation. In the absence of human studies, we used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate models of Parkinsonism to verify correlation between the SPECT, immunohistochemical and behavioural data. The DAT SPECT data correlated strongly and significantly with the substantia nigra pars compacta tyrosine hydroxylase and Nissl cell counts as well as the behavioural scores. Within the limitations of small numbers inherent to such studies, this data provides the first attempt at pathological validation of SPECT in primates.

In vivo plaque characterization using intravascular ultrasound-virtual histology in a porcine model of complex coronary lesions.

OBJECTIVE: To determine the accuracy of detection of different tissue types of intravascular ultrasound-virtual histology (IVUS-VH) in a porcine model of complex coronary lesions. METHODS AND RESULTS: Coronary lesions were induced by injecting liposomes containing human oxidized low-density lipoprotein into the adventitia of the arteries. IVUS-VH imaging was performed in vivo at 8.2+/-1.6 weeks after injection. A total of 60 vascular lesions were analyzed and compared with their correspondent IVUS-VH images. Correlation analysis was performed using linear regression models. Compared with histology, IVUS-VH correctly identified the presence of fibrous, fibro-fatty, and necrotic tissue in 58.33%, 38.33%, and 38.33% of lesions, respectively. The sensitivity of IVUS-VH for the detection of fibrous, fibro-fatty, and necrotic core tissue was 76.1%, 46%, and 41.1% respectively. A linear regression analysis performed for each individual plaque component did not show strong correlation that would allow significant prediction of individual values. CONCLUSIONS: In a porcine model of complex coronary lesions, IVUS-VH was not accurate in detecting the relative amount of specific plaque components within each individual corresponding histological specimen.