STAR procedure becomes SAFER: First-in-man case series of a new antegrade dissection re-entry technique

Introduction

Antegrade dissection and re-entry (ADR) is an integral part of the hybrid algorithm, which has allowed for improved outcomes in chronic total occlusion (CTO) coronary intervention (PCI).

Methods

A new ADR method, Subintimal Antegrade FEnestration and Re-entry (SAFER), is described. The results of a first-in-man series are presented.

Results

SAFER was performed on seven consecutive patients with angiographic and clinical success in all patients.

Conclusions

This first-in-man study has shown that the SAFER technique is feasible and effective with the possibility of improving the antegrade PCI CTO success rate.     

Assessment of aldehyde dehydrogenase in viable cells

Cytosolic aldehyde dehydrogenase (ALDH), an enzyme responsible for oxidizing intracellular aldehydes, has an important role in ethanol, vitamin A, and cyclophosphamide metabolism. High expression of this enzyme in primitive stem cells from multiple tissues, including bone marrow and intestine, appears to be an important mechanism by which these cells are resistant to cyclophosphamide. However, although hematopoietic stem cells (HSC) express high levels of cytosolic ALDH, isolating viable HSC by their ALDH expression has not been possible because ALDH is an intracellular protein. We found that a fluorescent aldehyde, dansyl aminoacetaldehyde (DAAA), could be used in flow cytometry experiments to isolate viable mouse and human cells based on their ALDH content. The level of dansyl fluorescence exhibited by cells after incubation with DAAA paralleled cytosolic ALDH levels determined by Western blotting and the sensitivity of the cells to cyclophosphamide. Moreover, DAAA appeared to be a more sensitive means of assessing cytosolic ALDH levels than Western blotting. Bone marrow progenitors treated with DAAA proliferated normally. Furthermore, marrow cells expressing high levels of dansyl fluorescence after incubation with DAAA were enriched for hematopoietic progenitors. The ability to isolate viable cells that express high levels of cytosolic ALDH could be an important component of methodology for identifying and purifying HSC and for studying cyclophosphamide-resistant tumor cell populations.     

Hematopoietic growth factors for graft failure after bone marrow transplantation: a randomized trial of granulocyte-macrophage colony- stimulating factor (GM-CSF) versus sequential GM-CSF plus granulocyte- CSF

Delay in hematologic recovery after bone marrow transplantation (BMT) can extend and amplify the risks of infection and hemorrhage, compromise patients' survival, and increase the duration and cost of hospitalization. Because current studies suggest that granulocyte- macrophage (GM) colony-stimulating factor (CSF) may potentiate the sensitivity of hematopoietic progenitor cells to G-CSF, we performed a prospective, randomized trial comparing GM-CSF (250 micrograms/m2/d x 14 days) versus sequential GM-CSF x 7 days followed by G-CSF (5 micrograms/kg/d x 7 days) as treatment for primary or secondary graft failure after BMT. Eligibility criteria included failure to achieve a white blood cell (WBC) count > or = 100/microL by day +21 or > or = 300/microL by day +28, no absolute neutrophil count (ANC) > or = 200/microL by day +28, or secondary sustained neutropenia after initial engraftment. Forty-seven patients were enrolled: 23 received GM-CSF (10 unrelated, 8 related allogeneic, and 5 autologous), and 24 received GM- CSF followed by G-CSF (12 unrelated, 7 related allogeneic, and 5 autologous). For patients receiving GM-CSF alone, neutrophil recovery (ANC > or = 500/microL) occurred between 2 and 61 days (median, 8 days) after therapy, while those receiving GM-CSF+G-CSF recovered at a similar rate of 1 to 36 days (median, 6 days; P = .39). Recovery to red blood cell (RBC) transfusion independence was slow, occurring 6 to 250 days (median, 35 days) after enrollment with no significant difference between the two treatment groups (GM-CSF: median, 30 days; GM-CSF+G- CSF; median, 42 days; P = .24). Similarly, platelet transfusion independence was delayed until 4 to 249 days (median, 32 days) after enrollment, with no difference between the two treatment groups (GM- CSF: median, 28 days; GM-CSF+G-CSF: median, 42 days; P = .38). Recovery times were not different between patients with unrelated donors and those with related donors or autologous transplant recipients. Survival at 100 days after enrollment was superior after treatment with GM-CSF alone. Only 1 of 23 patients treated with GM-CSF died versus 7 of 24 treated with GM-CSF+G-CSF who died 16 to 84 days (median, 38 days) after enrollment, yielding Kaplan-Meier 100-day survival estimates of 96% +/- 8% for GM-CSF versus 71% +/- 18% for GM-CSF+G-CSF (P = .026). These data suggest that sequential growth factor therapy with GM-CSF followed by G-CSF offers no advantage over GM-CSF alone in accelerating trilineage hematopoiesis or preventing lethal complications in patients with poor graft function after BMT.(ABSTRACT TRUNCATED AT 400 WORDS)     

Lung findings on high-resolution computed tomography in idiopathic ankylosing spondylitis--correlation with clinical findings, pulmonary function testing and plain radiography

Previous studies on the association of ankylosing spondylitis and abnormalities of the lung parenchyma have been based largely on plain radiography and pulmonary function testing. This study, although uncontrolled, is the first to use high-resolution computed tomography to examine the entire lung parenchyma in ankylosing spondylitis patients, and to correlate the findings with clinical assessment, plain radiography and pulmonary function testing. The study population comprised 26 patients meeting the New York criteria for idiopathic ankylosing spondylitis who attended the out-patient department at our institution. High-resolution computed tomography examination revealed abnormalities in 19 patients (70%): these included interstitial lung disease (n = 4), bronchiectasis (n = 6), emphysema (n = 4), apical fibrosis (n = 2), mycetoma (n = 1) and non-specific interstitial lung disease (n = 12). Plain radiography was abnormal in only four patients and failed to identify any patient with interstitial lung disease. All patients with interstitial lung disease on high-resolution computed tomography had respiratory symptoms and three of the four had evidence of a restrictive process on pulmonary function testing. This study raises, for the first time, the possible association between interstitial lung disease and ankylosing spondylitis, and highlights the use of high-resolution computed tomography in detecting such disease in ankylosing spondylitis patients.      

Clinical and echocardiographic correlates of health status in patients with acute chest pain

Objective  To assess the ability of echocardiographic data to predict important functional status outcomes in patients with chest pain. Design  Prospective cohort study. Setting  A large, urban teaching hospital. Patients  Three hundred thirty-three patients admitted from the Emergency Department for evaluation of chest pain. Measurements and Main Results  Patients underwent two-dimensional and Doppler echocardiography as well as a face-to-face interview during their initial hospitalization and a telephone interview 1 year thereafter. The interview included the Medical Outcomes Study 36-Item Short Form (SF-36) health inventory, a generic health status instrument with a physical function subscale. The relation between clinical and echocardiographic factors and functional status was explored by univariable and multivariable linear regression and logistic regression analyses. Multiple clinical and echocardiographic factors correlated significantly with functional status measures at 1 year. For the SF-36 score at 1 year, age, male gender, white race, the presence of rales, and a comorbidity score were independently predictors in multivariate analysis; echocardiographic findings of severe left ventricular dysfunction (parameter estimate [PE] −27.6; 95% confidence interval [CI] −43.1, −12.2) and aortic insufficiency (PE −16.7; 95% CI −26.4, −7.0) added independent predictive information. Explanatory power (r ²) for models using clinical and demographic variables was .27 and increased after inclusion of echocardiographic data to an r ² of .35. Results in the subset of patients (n=148) with acute coronary syndromes such as unstable angina or myocardial infarction were qualitatively similar. Selected factors (rales on examination, electrocardiographic changes suggestive of ischemia, and moderate to severe mitral regurgitation) also predicted which patients would die or have a decline in their functional status. In multivariate analysis, only rales remained an independent predictor of poor outcome (odds ratio 2.4; 95% CI 1.2, 4.5). Conclusions  Echocardiographic data are correlated with measures of functional status in patients with chest pain, but the ability to predict future functional status from clinical or echocardiographic information is limited. Because functional status cannot be predicted adequately from either patients’ characteristics or echocardiographic testing, it must be assessed directly. Dr. Fleischmann is the recipient of a Clinical Investigator Development Award (IK08HL02964-01) from the National Heart, Lung and Blood Institute.     

Risk Factors for Nosocomial Gastrointestinal Bleeding and Use of Acid-Suppressive Medication in Non-Critically Ill Patients

BACKGROUND

It is unknown whether there exist certain subsets of patients outside of the intensive care unit in whom the risk of nosocomial gastrointestinal bleeding is high enough that prophylactic use of acid-suppressive medication may be warranted.

OBJECTIVE

To identify risk factors for nosocomial gastrointestinal bleeding in a cohort of non-critically ill hospitalized patients, develop a risk scoring system, and use this system to identify patients most likely to benefit from acid suppression.

DESIGN

Cohort study.

PATIENTS

Adult patients admitted to an academic medical center from 2004 through 2007. Admissions with a principal diagnosis of gastrointestinal bleeding or a principal procedure code for cardiac catheterization were excluded.

MAIN MEASURES

Medication, laboratory, and other clinical data were obtained through electronic data repositories maintained at the medical center. The main outcome measure—nosocomial gastrointestinal bleeding occurring outside of the intensive care unit—was ascertained via ICD-9-CM coding and confirmed by chart review.

KEY RESULTS

Of 75,723 admissions (median age = 56 years; 40 % men), nosocomial gastrointestinal bleeding occurred in 203 (0.27 %). Independent risk factors for bleeding included age > 60 years, male sex, liver disease, acute renal failure, sepsis, being on a medicine service, prophylactic anticoagulants, and coagulopathy. Risk of bleeding increased as clinical risk score derived from these factors increased. Acid-suppressive medication was utilized in > 50 % of patients in each risk stratum. Our risk scoring system identified a high risk group in whom the number-needed-to-treat with acid-suppressive medication to prevent one bleeding event was < 100.

CONCLUSIONS

In this large cohort of non-critically ill hospitalized patients, we identified several independent risk factors for nosocomial gastrointestinal bleeding. With further validation at other medical centers, the risk model derived from these factors may help clinicians to direct acid-suppressive medication to those most likely to benefit..