Methylprednisolone, venous thromboembolism, and association with heparin to 30 days in hospital survival in severe Covid-19 pneumonia.

BACKGROUND: Mortality in severe COVID-19 pneumonia is associated with thrombo-inflammation. Corticosteroids are given to attenuate the inflammation, but they are associated with thrombosis. The aims of this study were to determine the risk of venous thromboembolism between no methylprednisolone and methylprednisolone (dose versus duration) and to evaluate any synergistic dose-dependent association of heparin and methylprednisolone to 30 days in hospital survival. METHODS: This was a secondary analysis of a retrospective cohort. Patients included in this study were ≥ 18 years of age and admitted for severe COVID-19 pneumonia between March and June 2020 in 13 hospitals in New Jersey, United States. A propensity score analysis between administration of methylprednisolone and no methylprednisolone was fitted for 11 variables and Youden Index Method was used to determine cut-off between low dose and high dose methylprednisolone. Multivariate cox regression was to assess risk. RESULTS: In 759 patients, the incidence of venous thromboembolism was 9% of patients who received methylprednisolone and 3% of patients who did not receive methylprednisolone with a [RR 2.92 (95% CI 1.54, 5.55 P < 0.0001)]. There was a higher incidence of mechanical ventilation in the methylprednisolone group. The median d-dimer between patients with venous thromboembolism was higher compared to those without (P < 0.0003). However, the d-dimer was not statistically significant between those who had venous thromboembolism between methylprednisolone and no methylprednisolone groups (P = 0.40). There was no higher risk in high dose versus low dose [RR = 0.524 (95% CI 0.26, 1.06 P 0.4)]; however, the risk for venous thromboembolism between methylprednisolone for > 7 days and ≤ 7 days was statistically significant (RR 5.46 95% CI 2.87, 10.34 P < 0.0001). Patients who received low dose methylprednisolone and therapeutic heparin had a trend towards higher risk of mortality compared to prophylactic heparin (HR 1.81 95% CI 0.994 to 3.294) (P = 0.0522). There was no difference in 30 days in hospital survival between high dose methylprednisolone with prophylactic or therapeutic heparin (HR 0.827 95% CI 0.514 to 1.33) (P = 0.4335). CONCLUSION: Methylprednisolone for > 7 days had a higher association of venous thromboembolism. There was no added benefit of therapeutic heparin to methylprednisolone on mechanically ventilated patients.

Outcomes of octogenarians undergoing gastrectomy performed for malignancy.

BACKGROUND: Studies on perioperative outcomes of octogenarians with gastric cancer are limited by small sample size. Our aim was to determine the outcomes of gastrectomy and the variation of treatments associated with advanced age (≥80 y). METHODS: The National Surgical Quality Improvement Program database was queried from 2005 to 2011. Patients who underwent gastrectomy for malignancy were identified using International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes. RESULTS: Of 2591 cases, 487 patients were octogenarians (≥80) and 2104 were nonoctogenarians (<80). Overall, 4.9% of patients had disseminated cancer. Octogenarians had higher 30-d mortality (7.2% versus 2.5%, P < 0.01) and more major complications (31.4% versus 25.5%, P < 0.01), though fewer octogenarians underwent total gastrectomy (24.0% versus 43.2%, P < 0.01) and extended lymphadenectomy (10.1% versus 17.4%, P < 0.01) than the nonoctogenarian cohort. On multivariate analysis, age ≥80 y was associated with major complications (OR, 1.3; 95% CI, 1.03-1.6; P = 0.03) and increased mortality (OR, 3.0; 95% CI, 1.9-4.9; P < 0.01). CONCLUSIONS: Advanced age (≥80 y) was associated with worse outcomes in patients undergoing gastrectomy for malignancy. Therefore, careful staging is necessary to reduce unnecessary operations in this population. Furthermore, surgeons must place greater attention on optimizing the octogenarian population before surgery.

The identification of risk factors for venous thromboembolism in gastrointestinal oncologic surgery.

BACKGROUND: The aim of this study was to examine the incidence and factors associated with occurrence of venous thromboembolism (VTE) in patients undergoing major gastrointestinal (GI) surgery for malignancy. METHODS: The American College of Surgeon's National Surgical Quality Improvement Program, Participant User File database was queried from 2005 to 2012 to study major GI operations performed for cancer. Predictors of VTE and their relation to survival were studied. RESULTS: In 79,300 patients, the incidence of deep venous thrombosis was 1.7%, and pulmonary embolism was 0.9% during the 30-d postoperative period. The highest rate of VTE occurred after esophagectomy (5.9%) followed by pancreatectomy (3.2%), hepatectomy (3.2%), gastrectomy (2.5%), enterectomy (2.3%), colectomy, and proctectomy (2.0%). On multivariate analysis, disseminated cancer, age ≥ 80 y, body mass index > 35 kg/m(2), functional status, post operative sepsis, pulmonary dysfunction, and longer operative time were associated with occurrence of VTE. Occurrence of VTE was associated with mortality on multivariate analysis (odds ratio 2.4, 95% confidence interval 2.0-3.0, P < 0.001). CONCLUSIONS: Absolute incidence of VTE after major GI surgery is low but is associated with significant mortality and postoperative complications. Disseminated cancer, post operative sepsis, longer operative time, and increased body mass index >35 kg/m(2) further increased the risk of VTE in patients undergoing surgery for malignancy. Surveillance strategies should be implemented for those cancer patients who have multiple risk factors for VTE.

Valacyclovir and Acyclovir Neurotoxicity With Status Epilepticus.

We present the case of a 52-year-old man with hypertension, diastolic congestive heart failure, end-stage renal disease on hemodialysis 3 times a week and a remote history of a hemorrhagic stroke who presented to the emergency department with a vesicular rash on his left arm. The rash was observed to be in a dermatomal distribution, and a diagnosis of herpes zoster was made. The patient was discharged home on valacyclovir 1 g 3 times a day for a duration of 7 days. The patient took 2 doses of valacyclovir before presenting to the hospital again with irritability and hallucinations. Over the next several days, the patient's neurologic status declined and he became disoriented and increasingly somnolent. Because of a concern for varicella zoster virus (VZV) or herpes simplex virus (HSV) meningoencephalitis, acyclovir was initiated intravenously at 600 mg (10 mg/kg) for every 12 hours. Computed tomography and magnetic resonance imaging of the brain failed to reveal an acute process. Electroencephalogram was interpreted as seizure activity versus metabolic encephalopathy. Lumbar puncture was not suggestive for meningitis, subarachnoid hemorrhage, or HSV/VZV infection. The patient subsequently had a witnessed seizure during dialysis and was felt to have status epilepticus due to acyclovir and valacyclovir neurotoxicity. The patient underwent daily hemodialysis for removal of the drug and eventually made a full neurologic recovery. Our case highlights that acyclovir neurotoxicity can result in status epilepticus, hallucinations, and altered consciousness. Differentiating acyclovir neurotoxicity from HSV or VZV meningoencephalitis is of crucial importance because the symptoms are similar but the management is vastly different.

Pulmonary complications after major abdominal surgery: National Surgical Quality Improvement Program analysis.

BACKGROUND: Postoperative pulmonary complications (PPCs) after major abdominal surgery are common and associated with significant morbidity and high cost of care. The objective of this study was to identify the risk factors for PPCs after major abdominal surgery. MATERIALS AND METHODS: The American College of Surgeons' National Surgical Quality Improvement Program database from 2005-2012 was queried for patients who underwent major abdominal surgery (esophagectomy, gastrectomy, pacnreatectomy, enterectomy, hepatectomy, colectomy, and proctectomy). Predictors of PPCs were identified using multivariate logistic regression. RESULTS: Of 165,196 patients who underwent major abdominal surgery 9595 (5.8%) suffered PPCs (pneumonia 3.2%, prolonged ventilator support ≥48 h 3.0%, and unplanned intubation 2.8%). On multivariate analysis, significant predictors of overall and individual PPCs include esophagectomy, advanced American Society of Anesthesiology Classification System, dependent functional status, prolonged operative time, age ≥80 y, severe chronic obstructive pulmonary disease, preoperative shock, ascites, and smoking. Obesity was not a risk factor. Female gender was overall protective for PPCs. CONCLUSIONS: PPCs after abdominal procedures are associated with a number of clinical variables. Esophageal operations and American Society of Anesthesiology Classification System were the strongest predictors. These results provide a framework for identifying patients at risk for developing pulmonary complications after major abdominal surgery.

The effects of neoadjuvant chemoradiation on pancreaticoduodenectomy­the American College of Surgeon's National Surgical Quality Improvement Program analysis.

BACKGROUND: The purpose of this study was to investigate the effects of preoperative chemoradiation therapy on postoperative outcomes of pancreaticoduodenectomy (PD). MATERIALS AND METHODS: The American College of Surgeon's National Surgical Quality Improvement Program Participant User File from 2005-2011 was used to analyze the outcomes of patients who underwent chemoradiation therapy before PD. Their outcomes were compared with those who underwent PD without neoadjuvant therapy. RESULTS: We identified 110 patients who received preoperative chemoradiation therapy before undergoing PD for pancreatic malignancies and compared them with 4915 patients who did not. The two groups were similar in their preoperative comorbidities and demographics. The neoadjuvant group experienced a significantly longer operative time with a higher rate of vascular reconstruction, transfusion requirement, and superficial wound infection compared with those who did not receive neoadjuvant therapy. However, mortality and the rate of major complications between the two groups were similar. CONCLUSIONS: Preoperative chemoradiation therapy is associated with an increase in transfusion requirement and superficial surgical site infection. However, it is not associated with an increase in 30-d mortality or major complications.

Predictors of mortality after emergency colectomy for Clostridium difficile colitis: an analysis of ACS-NSQIP.

OBJECTIVE: To evaluate clinical factors associated with mortality in emergency colectomies performed for Clostridium difficile colitis. BACKGROUND: The incidence and mortality from C difficile colitis is on the rise. Emergent colectomy performed for C difficile colitis is associated with a high mortality. METHODS: The ACS-NSQIP database from 2005 to 2010 was used to study emergently performed open colectomies for a primary diagnosis of C difficile colitis on the International Classification of Diseases, Ninth Revision. Preoperative, intraoperative, and postoperative factors were noted and compared between survivors and nonsurvivors. We performed multivariate stepwise binomial logistic regression analyses to study clinical factors that may be associated with 30-day mortality. RESULTS: The overall mortality for this cohort was 33% (111/335) with a median time to death of 8 days. On average, survivors were discharged on postoperative day 24. On multivariate analysis, those aged 80 years or older were associated with a ninefold increase in the odds of mortality [95% confidence interval (CI): 3.0-13.0]. Other factors associated with increased mortality were preoperative shock (OR=2.8, 95% CI: 1.6-5.4), preoperative dialysis dependence (OR=2.3, 95% CI: 1.1-4.8), chronic obstructive pulmonary disease (OR=3.7, 95% CI: 2.0-7.1), and wound class III (OR=2.1, 95% CI: 3.0-13). Thrombocytopenia (platelet count < 150×10(3)/mm(3)), coagulopathy (International Normalized Ratio>2.0), and renal insufficiency (blood urea nitrogen>40 mg/dL) were associated with a higher mortality as well. CONCLUSIONS: This is the largest series of colectomies performed for C difficile colitis in the literature. We identified several preoperative clinical risk factors that were associated with increased postoperative mortality. These findings may be useful in selecting appropriate patients for surgical intervention and may help to define a population where surgery may not be beneficial.

Survey of New York City resident physicians on cause-of-death reporting, 2010.

INTRODUCTION: Death certificates contain critical information for epidemiology, public health research, disease surveillance, and community health programs. In most teaching hospitals, resident physicians complete death certificates. The objective of this study was to examine the experiences and opinions of physician residents in New York City on the accuracy of the cause-of-death reporting system. METHODS: In May and June 2010, we conducted an anonymous, Internet-based, 32-question survey of all internal medicine, emergency medicine, and general surgery residency programs (n = 70) in New York City. We analyzed data by type of residency and by resident experience in reporting deaths. We defined high-volume respondents as those who completed 11 or more death certificates in the last 3 years. RESULTS: A total of 521 residents from 38 residency programs participated (program response rate, 54%). We identified 178 (34%) high-volume respondents. Only 33.3% of all respondents and 22.7% of high-volume residents believed that cause-of-death reporting is accurate. Of all respondents, 48.6% had knowingly reported an inaccurate cause of death; 58.4% of high-volume residents had done so. Of respondents who indicated they reported an inaccurate cause, 76.8% said the system would not accept the correct cause, 40.5% said admitting office personnel instructed them to "put something else," and 30.7% said the medical examiner instructed them to do so; 64.6% cited cardiovascular disease as the most frequent diagnosis inaccurately reported. CONCLUSION: Most resident physicians believed the current cause-of-death reporting system is inaccurate, often knowingly documenting incorrect causes. The system should be improved to allow reporting of more causes, and residents should receive better training on completing death certificates.

Methylprednisolone and 60 Days in Hospital Survival in Coronavirus Disease 2019 Pneumonia.

OBJECTIVES: To determine methylprednisolone's dose, duration, and administration from onset of symptoms and association with 60 days in hospital survival of coronavirus disease 2019 pneumonia. DESIGN: Cohort study. SETTING: Thirteen hospitals in New Jersey, United States during March to June 2020. PATIENTS: Seven-hundred fifty-nine hospitalized coronavirus disease 2019 patients. INTERVENTIONS: We performed a propensity matched cohort study between patients who received methylprednisolone and no methylprednisolone. Patients in the methylprednisolone group were further differentiated into dose (high dose and low dose), duration, and administration from onset of symptoms. MEASUREMENTS AND MAIN RESULTS: In the propensity matched sample, 99 out of 380 (26%) in no methylprednisolone, 69 out of 215 (31.9%) in low-dose methylprednisolone, and 74 out of 164 (55.2%) high-dose methylprednisolone expired. Overall median survival for no methylprednisolone (25.0 d), low-dose methylprednisolone (39.0 d), high-dose methylprednisolone (20.0 d), less than or equal to 7 days duration (19.0 d), 7-14 days duration (30.0 d), greater than 14 days duration (44.0 d), onset of symptoms less than or equal to 7 days (20.0 d), and onset of symptoms 7-14 days (27.0 d) were statistically significant (log-rank p ≤ 0.001). Multivariate Cox regression showed nursing home residents, coronary artery disease, and invasive mechanical ventilation were independently associated with mortality. Methylprednisolone was associated with reduced mortality compared with no methylprednisolone (hazard ratio, 0.40; 95% CI, 0.27-0.59; p < 0.001) but no added benefit with high dose. Low-dose methylprednisolone for 7-14 days was associated with reduced mortality compared with less than or equal to 7 days (hazard ratio, 0.45; 95% CI, 0.22-0.91; p = 0.0273), and no additional benefit if greater than 14 days (hazard ratio, 1.27; 95% CI, 0.60-2.69; p = 0.5434). Combination therapy with tocilizumab was associated with reduced mortality over monotherapy (p < 0.0116). CONCLUSIONS: Low-dose methylprednisolone was associated with reduced mortality if given greater than 7 days from onset of symptoms, and no additional benefit greater than 14 days. High dose was associated with higher mortality.

Clinical and laboratory evaluation of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma.

Here, we report on a phase IIa study to determine the intubation rate, survival, viral clearance, and development of endogenous Abs in patients with COVID-19 pneumonia treated with convalescent plasma (CCP) containing high levels of neutralizing anti-SARS-CoV-2 Abs. Radiographic and laboratory evaluation confirmed all 51 treated patients had COVID-19 pneumonia. Fresh or frozen CCP from donors with high titers of neutralizing Abs was administered. The nonmechanically ventilated patients (n = 36) had an intubation rate of 13.9% and a 30-day survival rate of 88.9%, and the overall survival rate for a comparative group based on network data was 72.5% (1625/2241). Patients had negative nasopharyngeal swab rates of 43.8% and 73.0% on days 10 and 30, respectively. Patients mechanically ventilated had a day-30 mortality rate of 46.7%; the mortality rate for a comparative group based on network data was 71.0% (369/520). All evaluable patients were found to have neutralizing Abs on day 3 (n = 47), and all but 1 patient had Abs on days 30 and 60. The only adverse event was a mild rash. In this study on patients with COVID-19 disease, we show therapeutic use of CCP was safe and conferred transfer of Abs, while preserving endogenous immune response.

Inhibition of Bruton tyrosine kinase in patients with severe COVID-19.

Patients with severe COVID-19 have a hyperinflammatory immune response suggestive of macrophage activation. Bruton tyrosine kinase (BTK) regulates macrophage signaling and activation. Acalabrutinib, a selective BTK inhibitor, was administered off-label to 19 patients hospitalized with severe COVID-19 (11 on supplemental oxygen; 8 on mechanical ventilation), 18 of whom had increasing oxygen requirements at baseline. Over a 10-14 day treatment course, acalabrutinib improved oxygenation in a majority of patients, often within 1-3 days, and had no discernable toxicity. Measures of inflammation - C-reactive protein and IL-6 - normalized quickly in most patients, as did lymphopenia, in correlation with improved oxygenation. At the end of acalabrutinib treatment, 8/11 (72.7%) patients in the supplemental oxygen cohort had been discharged on room air, and 4/8 (50%) patients in the mechanical ventilation cohort had been successfully extubated, with 2/8 (25%) discharged on room air. Ex vivo analysis revealed significantly elevated BTK activity, as evidenced by autophosphorylation, and increased IL-6 production in blood monocytes from patients with severe COVID-19 compared with blood monocytes from healthy volunteers. These results suggest that targeting excessive host inflammation with a BTK inhibitor is a therapeutic strategy in severe COVID-19 and has led to a confirmatory international prospective randomized controlled clinical trial.

Hydroxychloroquine and tocilizumab therapy in COVID-19 patients-An observational study.

Hydroxychloroquine has been touted as a potential COVID-19 treatment. Tocilizumab, an inhibitor of IL-6, has also been proposed as a treatment of critically ill patients. In this retrospective observational cohort study drawn from electronic health records we sought to describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients. Patients were hospitalized at a 13-hospital network spanning New Jersey USA between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2. Follow up was through May 5, 2020. Among 2512 hospitalized patients with COVID-19 there have been 547 deaths (22%), 1539 (61%) discharges and 426 (17%) remain hospitalized. 1914 (76%) received at least one dose of hydroxychloroquine and 1473 (59%) received hydroxychloroquine with azithromycin. After adjusting for imbalances via propensity modeling, compared to receiving neither drug, there were no significant differences in associated mortality for patients receiving any hydroxychloroquine during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), hydroxychloroquine alone (HR, 1.02 [95% CI, 0.83-1.27]), or hydroxychloroquine with azithromycin (HR, 0.98 [95% CI, 0.75-1.28]). The 30-day unadjusted mortality for patients receiving hydroxychloroquine alone, azithromycin alone, the combination or neither drug was 25%, 20%, 18%, and 20%, respectively. Among 547 evaluable ICU patients, including 134 receiving tocilizumab in the ICU, an exploratory analysis found a trend towards an improved survival association with tocilizumab treatment (adjusted HR, 0.76 [95% CI, 0.57-1.00]), with 30 day unadjusted mortality with and without tocilizumab of 46% versus 56%. This observational cohort study suggests hydroxychloroquine, either alone or in combination with azithromycin, was not associated with a survival benefit among hospitalized COVID-19 patients. Tocilizumab demonstrated a trend association towards reduced mortality among ICU patients. Our findings are limited to hospitalized patients and must be interpreted with caution while awaiting results of randomized trials. Trial Registration: Clinicaltrials.gov Identifier: NCT04347993.

Cysteine-reactive covalent capture tags for enrichment of cysteine-containing peptides.

Considering the tremendous complexity and the wide dynamic range of protein samples from biological origin and their proteolytic peptide mixtures, proteomics largely requires simplification strategies. One common approach to reduce sample complexity is to target a particular amino acid in proteins or peptides, such as cysteine (Cys), with chemical tags in order to reduce the analysis to a subset of the whole proteome. The present work describes the synthesis and the use of two new cysteinyl tags, so-called cysteine-reactive covalent capture tags (C3T), for the isolation of Cys-containing peptides. These bifunctional molecules were specifically designed to react with cysteines through iodoacetyl and acryloyl moieties and permit efficient selection of the tagged peptides. To do so, a thioproline was chosen as the isolating group to form, after a deprotection/activation step, a thiazolidine with an aldehyde resin by the covalent capture (CC) method. The applicability of the enrichment strategy was demonstrated on small synthetic peptides as well as on peptides derived from digested proteins. Mass spectrometric (MS) analysis and tandem mass spectrometric (MS/MS) sequencing confirmed the efficient and straightforward selection of the cysteine-containing peptides. The combination of C3T and CC methods provides an effective alternative to reduce sample complexity and access low abundance proteins.

A novel method for creating custom shaped ballistic gelatin trainers using plaster molds.

Simulation based procedural training is an effective and frequently used method for teaching vascular access techniques which often require commercial trainers. These can be prohibitively expensive, which allows for homemade trainers made of gelatin to be a more cost-effective and attractive option. Previously described trainers are often rectangular with a flat surface that is dissimilar to human anatomy. We describe a novel method to create a more anatomically realistic trainer using ballistic gelatin, household items, and supplies commonly found in an emergency department such as the plaster wrap typically used to make splints.

Diaphragm Muscle Thinning in Subjects Receiving Mechanical Ventilation and Its Effect on Extubation.

BACKGROUND: Diaphragm muscle weakness and atrophy are consequences of prolonged mechanical ventilation. Our purpose was to determine whether thickness of the diaphragm (TDI) changes over time after intubation and whether the degree of change affects clinical outcome. METHODS: For this prospective, longitudinal observational study, we identified subjects who required mechanical ventilation and measured their TDI by ultrasonography. TDI was measured at baseline and repeated 72 h later and then weekly until the subject was either liberated from mechanical ventilation, was referred for tracheostomy, or died. The analysis was designed to determine whether baseline TDI and change in TDI affect extubation outcome. RESULTS: Of the 57 subjects who underwent both diaphragm measurements at 72 h, 16 died, 33 were extubated, and 8 underwent tracheostomy. Only 14 subjects received mechanical ventilation for 1 week, and 2 subjects received mechanical ventilation for 2 and 3 weeks. Females had significantly thinner baseline TDI (P = .008). At 72 h, TDI had decreased in 84% of subjects. We found no significant association between the rate of thinning and sex (P = .68), diagnosis of COPD (P = .36), current smoking (P = .85), or pleural effusion (P = .83). Lower baseline TDI was associated with higher likelihood of extubation: 12.5% higher for every 0.01-cm decrease in TDI (hazard ratio 0.875, 95% CI 0.80-0.96, P = .003). For every 0.01-cm decrease in TDI at 72 h, the likelihood of extubation increased by 17% (hazard ratio 0.83, 95% CI 0.70-0.99, P = .041). CONCLUSIONS: Although most of the subjects showed evidence of diaphragm thinning, we were unable to find a correlation with outcome of extubation failure. In fact, the thinner the diaphragm at baseline and the greater the extent of diaphragm thinning at 72 h, the greater the likelihood of extubation. Thickening ratio or other measurement may be a more reliable indicator of diaphragm dysfunction and should be explored.

Characterisation of preproendothelin-1 derived peptides identifies Endothelin-Like Domain Peptide as a modulator of Endothelin-1.

Endothelin-1 (ET-1) is involved in the pathogenesis of cardiac and renal diseases, and in the progression of tumour growth in cancer, but current diagnosis and treatment remain inadequate. Peptides derived from the 212 amino acid precursor preproendothelin-1 (ppET-1) may have utility as biomarkers, or cause biological effects that are unaffected by endothelin receptor antagonists. Here, we used specific immunoassays and LC-MS/MS to identify NT-proET-1 (ppET-1[18-50]), Endothelin-Like Domain Peptide (ELDP, ppET-1[93-166]) and CT-proET-1 (ppET-1[169-212]) in conditioned media from cultured endothelial cells. Synthesis of these peptides correlated with ET-1, and plasma ELDP and CT-proET-1 were elevated in patients with chronic heart failure. Clearance rates of NT-proET-1, ELDP and CT-proET-1 were determined after i.v. injection in anaesthetised rats. CT-proET-1 had the slowest systemic clearance, hence providing a biological basis for it being a better biomarker of ET-1 synthesis. ELDP contains the evolutionary conserved endothelin-like domain sequence, which potentially confers biological activity. On isolated arteries ELDP lacked direct vasoconstrictor effects. However, it enhanced ET-1 vasoconstriction and prolonged the increase in blood pressure in anaesthetised rats. ELDP may therefore contribute to disease pathogenesis by augmenting ET-1 responses.

Discovery of proteins related to coronary artery disease using industrial-scale proteomics analysis of pooled plasma.

BACKGROUND: Relating a disease state to an entire population of proteins provides an opportunity to gain new insights into a disease. METHODS: Male populations of 53 patients with angiographic coronary artery disease and 53 control subjects without coronary disease from the Duke Databank for Cardiovascular Disease were established and matched for age and race as well as extremes of risk factors. Major plasma protein abnormalities were excluded. Plasma samples of each group were pooled to make large volumes (6 L each) to identify low-abundance proteins. After removal of albumin as well as immunoglobulins and enrichment of smaller proteins (<20-40 kDa), samples were separated into 12,960 fractions by cation exchange and 2 reversed-phase chromatography steps. Proteins were analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry. RESULTS: There were 731 plasma proteins or fragments identified. Of these proteins, 95 were differentially displayed in the case versus control populations. These represent broad categories of proteins involved with natural defenses, inflammation, growth, and coagulation. CONCLUSION: We identified a large number of proteins that differ in abundance in populations with and those without angiographic coronary disease. These proteins now comprise candidates for validation studies in individual patients and in larger clinical data sets to better define disease pathways and establish novel markers for disease.

Simulation-based training for emergency medicine residents in sterile technique during central venous catheterization: impact on performance, policy, and outcomes.

OBJECTIVES: Central line-associated bloodstream infection (CLABSI) is a preventable nosocomial infection. Simulation-based training in sterile technique during central venous catheter (CVC) placement for emergency medicine (EM) residents, and its effect on changing the medical intensive care unit (MICU) practice of routine replacement of CVCs placed under sterile technique in the emergency department (ED), has not been evaluated. METHODS: Emergency medicine residents received simulation-based sterile technique training during CVC placement between May 2008 and September 2010. Between June 2008 and January 2011, the authors reviewed records of patients who had CVCs placed in the ED under sterile technique by EM residents and were admitted to the MICU (group 1) and CVCs placed in the MICU under sterile technique by internal medicine (IM) residents (group 2). IM residents completed similar simulation-based training before May 2008. Changes in EM residents' sterile technique performance scores were compared, as well as CLABSI rates in both groups. EM residents' CVC procedural skills were not assessed. RESULTS: Seventy-six EM residents completed simulation-based training with significant improvement in performance (median scores 13 out of 24 before training, 24 out of 24 after training; p < 0.001). CLABSI rates per 1,000 catheter-days were 1.02 in group 1 and 1.02 in group 2 (p = 0.99). Both groups had similar demographics, acuity, and mortality (p > 0.5). CONCLUSIONS: Routine replacement of CVCs placed in the ED under sterile technique after simulation-based training would appear to be unnecessary. These findings demonstrate patient-centered outcomes that are comparable for CVCs in ED-admitted MICU patients, regardless of whether the CVC was placed in the ED or MICU.